ArticleLiterature Review

Efficacy and Safety of Magnesium for the Management of Chronic Pain in Adults: A Systematic Review

February 2020
Anesthesia & Analgesia Publish Ahead of Print(3):1

Authors:

Queen's University

Chronic pain is a highly prevalent and complex health problem that is associated with a heavy symptom burden, substantial economic and social impact, and also, very few highly effective treatments. This review examines evidence for the efficacy and safety of magnesium in chronic pain. The previously published protocol for this review was registered in International Prospective Register of Systematic Reviews (PROSPERO), MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched until September 2018. We included randomized controlled trials (RCTs) comparing magnesium (at any dose, frequency, or route of administration) with placebo using participant-reported pain measures. A total of 9 RCTs containing 418 participants were included. Three studies examined neuropathic pain (62 participants), 3 examined migraines (190 participants), 2 examined complex regional pain syndrome (86 participants), and 1 examined low back pain with a neuropathic component (80 participants). Heterogeneity of included studies precluded any meta-analyses. No judgement could be made about safety because adverse events were inconsistently reported in the included studies. Evidence of analgesic efficacy from included studies was equivocal. However, reported efficacy signals in some of the included trials provide a rationale for more definitive studies. Future, larger-sized trials with good assay sensitivity and better safety assessment and reporting, as well as careful attention to formulations with optimal bioavailability, will serve to better define the role of magnesium in the management of chronic pain.

Magnesium and Migraine

Article

Full-text available

Feb 2025

Migraine is a widespread and intricate neurological condition that involves various factors and is marked by recurring headache episodes. Migraine is among the ten neurological conditions accounting for the greatest disability in the whole population, the leading cause of disability for children and adolescents aged 5–19 years, and the second cause of disability for adults aged 20–59 years. Magnesium deficiency is also a very common condition resulting from diverse reasons, including insufficient dietary consumption or increased loss through the gastrointestinal or renal system. Accumulated evidence from case reports, case–control studies, observational studies, and randomized, placebo-controlled trials has shown the effectiveness of magnesium supplementation in alleviating migraine, both acutely and chronically. Mechanisms that may help explain these results include the potential link between magnesium deficit and spreading cortical depression, vascular changes, oxidative stress, chronic inflammation, nervous excitation, neurotransmitter release, and electrolyte imbalances. This article aims to provide a comprehensive review of the available evidence on the links between magnesium and migraine, considering the role of magnesium in the pathogenesis of migraine and the utility of magnesium in its prevention and treatment.

A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Therapeutic Effect of Magnesium-L-Threonate Supplementation for Persistent Pain After Breast Cancer Surgery

Article

Full-text available

Jul 2023

Purpose Post-mastectomy pain syndrome is a common yet debilitating neuropathic complication after breast cancer procedures, resulting in significantly reduced quality of life. Recently, emerging evidence has supported the therapeutic effect of magnesium administration in chronic pain. However, the role of magnesium supplementation in development of chronic pain after breast cancer surgery remains less known. The aim of this study was to evaluate therapeutic effect of magnesium supplementation on persistent pain after breast cancer procedure. Patients and Methods This was a randomized, double-blind, placebo-controlled clinical trial. A total of 109 patients who underwent breast cancer procedure received magnesium-L-threonate (n = 48) or placebo (n = 61) for 12 weeks. Chronic pain incidence, short form of the McGill Pain Questionnaire (SF-MPQ), Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Telephone Interview for Cognitive Status (TICS) were evaluated at 3- and 6-month follow-up. Results About 31% (15 out of 48) of patients reported chronic pain after magnesium supplementation, and 26% (16 out of 61) of the control group at 6-month follow-up respectively. Total scores of SF-MPQ were significantly increased in the control group 6 months after surgical intervention (mean difference, 1.475; 95% CI, −2.730 to −0.2211), but NOT in the magnesium treated group (mean difference, 1.250; 95% CI, −2.775 to 0.2748). No significant differences were found between two cohorts on SF-MPQ, GAD-7, PHQ-9, PSQI, or TICS at each timepoint. Conclusion Oral supplementation of magnesium-L-threonate did not effectively prevent the development of persistent pain in breast cancer survivors, nor provide sufficient pain relief over placebo. We did not observe improvement of pain, mood, sleep disorder, or cognitive function after 12-week magnesium supplementation. Future study may focus on magnesium combined with other effective anti-neuropathic pain treatment.

N-Methyl-D-aspartate receptor antagonists for the prevention of chronic postsurgical pain: a narrative review

Article

Feb 2025
REGION ANESTH PAIN M

The N-methyl-D-aspartate receptor (NMDAR) has been linked to the development of chronic postsurgical pain (CPSP), defined as pain after surgery that does not resolve by 3 months. Once the combination of a painful stimulus and glutamate binding activates the NMDAR, calcium influx triggers signaling cascades that lead to processes like central sensitization and CPSP. Three of the most widely studied perioperative NMDAR antagonists include ketamine, magnesium, and methadone, with ketamine having garnered the greatest amount of attention. While multiple studies have found improved analgesia in the acute postoperative period, fewer studies have focused on long-term outcomes and those that have are often underpowered for CPSP or have not included those patients at highest risk. Existing meta-analyses of ketamine for CPSP are inconsistent in their findings, and studies of magnesium and methadone are even more limited. Overall, the evidence supporting NMDAR antagonists for CPSP is weak and we recommend that future studies focus on high-risk patients and potentially include combinations of NMDAR antagonists administered together for the longest duration feasible. The results of ongoing trials could have a major influence on the overall direction of the evidence supporting NMDAR antagonists in preventing CPSP.

Analgesic Effects of Magnesium Sulphate In Patients Undergoing Laparoscopic Cholecystectom

Article

Full-text available

Nov 2024

Objective: To assess the effectiveness of intraoperative administration of MgSO4 in achieving satisfactory postoperative pain relief following laparoscopic surgery. Study Design: Quasi-experimental research. Place and Duration of Study: Combined Military Hospital, Rawalpindi Pakistan, Apr to Sep 2021. Methodology: A total of 200 patients gave their informed consent before being split into two groups of 100. Patients were given Tablet Alprazolam 0.25mg and Omeprazole 20mg the night before surgery and again on the morning of surgery, and were asked for NPO for 8 hours before to surgery. Group 1 got 50 mg/kg of magnesium sulphate diluted in 250 ml of isotonic 0.9% normal saline intravenously during surgery, while Group 2 received the same volume of isotonic 0.9% normal saline. Results: Administering intravenous magnesium sulphate at an intravenous dose of 50 milligrams per kilogram of body weight before laryngoscopy and intubation significantly reduces the need for post-operative pain medication by reducing post-operative pain and delaying its onset. Additionally, it reduces the amount of pain medication required after surgery. Therefore, overall, pretreatment with magnesium sulphate has a significant impact on post-operative pain management. Conclusion: Magnesium sulphate is an excellent analgesic for people undergoing laparoscopic cholecystectomy.

Assessing the Effects of HbA1c Reduction on Alleviating Chronic Nonspecific Low Back Pain in Prediabetic Non-obese Patients: A Non-Randomized Controlled Trial

Article

Full-text available

Nov 2024

Background Pre-diabetes, characterized by elevated glycemic indices, poses a high risk of diabetes development, and is increasingly linked to non-specific low back pain. While mechanisms remain incompletely understood, metabolic, inflammatory, and neurological factors are implicated. Dietary interventions, including low-glycemic and anti-inflammatory diets, alongside weight management, may improve outcomes in this population. Objectives In this non-randomized controlled trial, we aim to evaluate the influence of decreasing HbA1c levels on reducing chronic non-specific low back pain in pre-diabetic, non-obese individuals, as well as emphasizing the importance of such a study in supporting the literature. Methods A non-randomized controlled single-blind clinical trial was conducted among 82 participants with chronic non-specific low back pain and pre-diabetes at an outpatient clinic in Baghdad from the 30th of January to the 22nd of September. The intervention methods aimed at reducing HbA1c levels to assess the reduction impact on alleviating chronic non-specific low back pain included dietary adjustments, sleep optimization, and correction of vitamins and minerals deficiencies. The follow-up process was conducted individually for each participant, with a monthly assessment over a period of six months. Results At 12 weeks a significant decrease in chronic non-specific low back pain severity was observed in patients with lower HbA1C levels yielding a P-value of .021. Similarly, at 24 weeks there was a decline in the number of patients who reported chronic non-specific low back pain, and the association to lower HbA1C levels was significant with a p-value of .005. Conclusion This study suggests the presence of a statistically significant association between reduction of HbA1C levels and ensuing improvement in chronic non-specific low back pain symptoms in non-obese prediabetic patients.

Efficacy and safety of sublingual buprenorphine in managing acute postoperative pain – A systematic review

Article

Full-text available

Jul 2024

Sublingual (SL) buprenorphine has been used as a modality of managing acute postoperative pain in many studies. This systematic review aimed to investigate the safety and efficacy of SL buprenorphine as an analgesic for various surgeries. After registering the protocol with PROSPERO, we searched PubMed, Cochrane Library, and Ovid databases with relevant keywords. The primary outcomes were 24-hour pain scores, and the secondary outcomes were postoperative nausea and vomiting, sedation scores, pruritus, rescue analgesia, and urinary retention. The risk of bias scale was used to identify the quality of evidence. From the 103 articles identified, four randomized-controlled trials fulfilled the inclusion criteria for qualitative analysis. The overall risk of bias was low. Most of the studies showed that the use of SL buprenorphine led to either better or comparable pain scores when compared to a control group with lesser or tolerable adverse events. There was a lot of heterogeneity across the studies in this systematic review in terms of the type of surgery performed, the comparison groups, doses of buprenorphine, and the outcomes that were assessed. Therefore, a quantitative meta-analysis was not performed. The results of this systematic review should be interpreted with caution due to heterogeneity in the methodology. Adequately powered studies with robust methodology should investigate the safety and efficacy of SL buprenorphine when used for postoperative analgesia.

A systematic review and network meta-analysis of pharmaceutical interventions used to manage chronic pain

Article

Full-text available

Jan 2024

It is estimated 1.5 billion of the global population suffer from chronic pain with prevalence increasing with demographics including age. It is suggested long-term exposure to chronic could cause further health challenges reducing people’s quality of life. Therefore, it is imperative to use effective treatment options. We explored the current pharmaceutical treatments available for chronic pain management to better understand drug efficacy and pain reduction. A systematic methodology was developed and published in PROSPERO (CRD42021235384). Keywords of opioids, acute pain, pain management, chronic pain, opiods, NSAIDs, and analgesics were used across PubMed, Science direct, ProQuest, Web of science, Ovid Psych INFO, PROSPERO, EBSCOhost, MEDLINE, ClinicalTrials.gov and EMBASE. All randomised controlled clinical trials (RCTs), epidemiology and mixed-methods studies published in English between the 1st of January 1990 and 30th of April 2022 were included. A total of 119 studies were included. The data was synthesised using a tri-partied statistical methodology of a meta-analysis (24), pairwise meta-analysis (24) and network meta-analysis (34). Mean, median, standard deviation and confidence intervals for various pain assessments were used as the main outcomes for pre-treatment pain scores at baseline, post-treatment pain scores and pain score changes of each group. Our meta-analysis revealed the significant reduction in chronic pain scores of patients taking NSAID versus non-steroidal opioid drugs was comparative to patients given placebo under a random effects model. Pooled evidence also indicated significant drug efficiency with Botulinum Toxin Type-A (BTX-A) and Ketamine. Chronic pain is a public health problem that requires far more effective pharmaceutical interventions with minimal better side-effect profiles which will aid to develop better clinical guidelines. The importance of understanding ubiquity of pain by clinicians, policy makers, researchers and academic scholars is vital to prevent social determinant which aggravates issue.

Occupational and non-occupational risk factors correlating with the severity of clinical manifestations of carpal tunnel syndrome and related work disability among workers who work with a computer

Article

Full-text available

Dec 2023

The contribution of certain occupational and personal factors to the development of carpal tunnel syndrome (CTS) is still uncertain. We investigated which specific occupational and non-occupational factors correlate with the level of clinical manifestations and work disability related to CTS. The study included 190 workers who work with a computer and have diagnosed CTS (100 men, 90 women, aged 20–65 years). Subjective experience of CTS-related impairments was assessed with the Symptom Severity Scale (SSS) and the Functional Status Scale (FSS) of the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ). The objective, neural impairments were tested with electrodiagnostics (EDX), whereas CTS-related work disability data were collected from medical records. We found a high inter-correlation between BCTQ, EDX, and work disability data. These also showed high correlations with certain occupational factors (duration of computer-working in months and hours spent daily in computer-working, certain ergonomic, microclimatic, and other occupational conditions) and non-occupational factors (demographic and lifestyle factors: nutritional status, diet, smoking, alcohol consumption, and physical activity). Despite its limitations, our study has identified occupational and non-occupational risk factors that can aggravate CTS and work disability, but which can also be improved with workplace and lifestyle preventive and corrective measures. More research is needed, though, to establish the possible causal relationships and the independent influence of each of those risk factors.

Systematic reviews and meta-analyses in regional anesthesia and pain medicine (Part I): guidelines for preparing the review protocol

Article

Nov 2023

Comprehensive resources exist on how to plan a systematic review and meta-analysis. The objective of this article is to provide guidance to authors preparing their systematic review protocol in the fields of regional anesthesia and pain medicine. The focus is on systematic reviews of healthcare interventions, with or without an aggregate data meta-analysis. We describe and discuss elements of the systematic review methodology that review authors should prespecify, plan, and document in their protocol before commencing the review. Importantly, authors should explain their rationale for planning their systematic review and describe the PICO framework—participants (P), interventions (I),comparators (C), outcomes (O)—and related elements central to constructing their clinical question, framing an informative review title, determining the scope of the review, designing the search strategy, specifying the eligibility criteria, and identifying potential sources of heterogeneity. We highlight the importance of authors defining and prioritizing the primary outcome, defining eligibility criteria for selecting studies, and documenting sources of information and search strategies. The review protocol should also document methods used to evaluate risk of bias, quality (certainty) of the evidence, and heterogeneity of results. Furthermore, the authors should describe their plans for managing key data elements, the statistical construct used to estimate the intervention effect, methods of evidence synthesis and meta-analysis, and conditions when meta-analysis may not be possible, including the provision of practical solutions. Authors should provide enough detail in their protocol so that the readers could conduct the study themselves.

Systematic reviews and meta-analyses in regional anesthesia and pain medicine (Part II): guidelines for performing the systematic review

Article

Nov 2023

In Part I of this series, we provide guidance for preparing a systematic review protocol. In this article, we highlight important steps and supplement with exemplars on conducting and reporting the results of a systematic review. We suggest how authors can manage protocol violations, multiplicity of outcomes and analyses, and heterogeneity. The quality (certainty) of the evidence and strength of recommendations should follow the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. It is our goal that Part II of this series provides valid guidance to authors and peer reviewers who conduct systematic reviews to adhere to important constructs of transparency, structure, reproducibility, and accountability. This will likely result in more rigorous systematic reviews being submitted for publication to the journals like Regional Anesthesia & Pain Medicine and Anesthesia & Analgesia .

Systematic Reviews and Meta-analyses in Regional Anesthesia and Pain Medicine (Part I): Guidelines for Preparing the Review Protocol

Article

Nov 2023

Comprehensive resources exist on how to plan a systematic review and meta-analysis. The objective of this article is to provide guidance to authors preparing their systematic review protocol in the fields of regional anesthesia and pain medicine. The focus is on systematic reviews of health care interventions, with or without an aggregate data meta-analysis. We describe and discuss elements of the systematic review methodology that review authors should prespecify, plan, and document in their protocol before commencing the review. Importantly, authors should explain their rationale for planning their systematic review and describe the PICO framework—participants (P), interventions (I), comparators (C), outcomes (O)—and related elements central to constructing their clinical question, framing an informative review title, determining the scope of the review, designing the search strategy, specifying the eligibility criteria, and identifying potential sources of heterogeneity. We highlight the importance of authors defining and prioritizing the primary outcome, defining eligibility criteria for selecting studies, and documenting sources of information and search strategies. The review protocol should also document methods used to evaluate risk of bias, quality (certainty) of the evidence, and heterogeneity of results. Furthermore, the authors should describe their plans for managing key data elements, the statistical construct used to estimate the intervention effect, methods of evidence synthesis and meta-analysis, and conditions when meta-analysis may not be possible, including the provision of practical solutions. Authors should provide enough detail in their protocol so that the readers could conduct the study themselves.

A Systematic review and Network Meta-analysis of pharmaceutical interventions used to manage chronic pain

Preprint

Full-text available

Sep 2023

Background: It is estimated 1·5 billion of the global population suffer from chronic pain with prevalence increasing with demographics including age. It is suggested long-term exposure to chronic could cause further health challenges reducing people’s quality of life. Therefore, it is imperative to use effective treatment options. We explored the current pharmaceutical treatments available for chronic pain management to better understand drug efficacy and pain reduction. Methods: A systematic methodology was developed and published in PROSPERO (CRD42021235384). Keywords of opioids, acute pain, pain management, chronic pain, opiods, NSAIDs, and analgesics were used across PubMed, Science direct, ProQuest, Web of science, Ovid Psych INFO, PROSPERO, EBSCOhost, MEDLINE, ClinicalTrials.gov and EMBASE. All randomised controlled clinical trials (RCTs), epidemiology and mixed-methods studies published in English between the 1st of January 1990 and 30th of April 2022 were included. A total of 119 studies were included. The data was synthesised using a tri-partied statistical methodology of a meta-analysis (24), pairwise meta-analysis (24) and network meta-analysis (34). Mean, median, standard deviation and confidence intervals for various pain assessments were used as the main outcomes for pre-treatment pain scores at baseline, post-treatment pain scores and pain score changes of each group. Findings: Our meta-analysis revealed the significant reduction in chronic pain scores of patients taking NSAID versus non-steroidal opioid drugs was comparative to patients given placebo under a random effects model. Pooled evidence also indicated significant drug efficiency with Botulinum Toxin Type-A (BTX-A) and Ketamine. Conclusion: Chronic pain is a public health problem that requires far more effective pharmaceutical interventions with minimal better side-effect profiles which will aid to develop better clinical guidelines. The importance of understanding ubiquity of pain by clinicians, policy makers, researchers and academic scholars is vital to prevent social determinant which aggravates issue.

Analgesic efficacy and safety of duloxetine premedication in patients undergoing hysterectomy – A systematic review

Article

Full-text available

Sep 2023

Background and Aims Patients undergoing hysterectomy by open or laparoscopic approach experience moderate to severe postoperative pain. A multimodal analgesic approach is recommended for these patients. This study reviews the analgesic efficacy of duloxetine, a selective serotonin and norepinephrine reuptake inhibitor used as an adjuvant for opioid-sparing postoperative analgesia. Methods After registering the protocol in the international prospective register of systematic reviews (PROSPERO), databases like PubMed, Ovid, Scopus, Cochrane Library and clinicaltrials.gov were searched for randomised controlled trials using relevant keywords to find studies in which duloxetine premedication was compared to a placebo in patients undergoing hysterectomy. The revised Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to assess the quality of evidence. Results The qualitative systematic review included five of the 88 studies identified. The overall risk of bias in the included studies was very high. In all the studies, 60 mg oral duloxetine was used, and the control group was placebo. In two studies, duloxetine premedication was administered 2 h before and 24 h after surgery. In the other three studies, a single dose of 60 mg duloxetine was only administered 2 h before surgery. A pooled meta-analysis was not performed due to fewer studies that fulfilled the inclusion criteria and even fewer studies with consistent reporting of various outcomes. Conclusion The evidence is insufficient to advocate routine duloxetine premedication in patients undergoing hysterectomy.

Use of complementary and alternative medicine by patients with hypermobile Ehlers–Danlos Syndrome: A qualitative study

Article

Full-text available

Dec 2022

Background Patients with hypermobile Ehlers–Danlos Syndrome (hEDS) often make use of complementary and alternative medical (CAM) techniques to manage their chronic pain and other symptoms. Nevertheless, how they use CAM, which techniques they favor, and how CAM use affects their allopathic care remain unclear. The purpose of this qualitative study was to understand patients’ personal experiences with CAM and its role in their symptom management. Materials and methods Thirty individuals living with hEDS completed a brief online survey related to their CAM use. Thereafter, in-depth interviews were conducted with 24 of the survey respondents, qualitatively investigating their experiences with CAM. Data were analyzed using thematic analysis. Results Participants described massage therapy ( N = 21), medical cannabis ( N = 12), and mindfulness ( N = 13) as some of the most useful CAM modalities for managing symptoms related to hEDS, but they expressed a general interest in pursuing any treatment that could potentially reduce their chronic pain. They suggested an overall trust in CAM modalities and practitioners and ascribed greater empathy to CAM practitioners than to conventional medical providers. However, they also described a critical skepticism of CAM (and conventional) therapies and recounted instances of injury from such treatments. Conclusion Participants made extensive use of CAM therapies. They described both critical benefits as well as harms from the use of these non-conventional modalities. These results underscore the importance of clinicians maintaining communicative and compassionate relationships with their patients, and of an openness to the discussion and use of CAM treatments.

Short-Term Magnesium Therapy Alleviates Moderate Stress in Patients with Fibromyalgia: A Randomized Double-Blind Clinical Trial

Article

Full-text available

May 2022

Patients suffering from fibromyalgia often report stress and pain, with both often refractory to usual drug treatment. Magnesium supplementation seems to improve fibromyalgia symptoms, but the level of evidence is still poor. This study is a randomized, controlled, double-blind trial in fibromyalgia patients that compared once a day oral magnesium 100 mg (Chronomag®, magnesium chloride technology formula) to placebo, for 1 month. The primary endpoint was the level of stress on the DASS-42 scale, and secondary endpoints were pain, sleep, quality of life, fatigue, catastrophism, social vulnerability, and magnesium blood concentrations. After 1 month of treatment, the DASS-42 score decreased in the magnesium and placebo groups but not significantly (21.8 ± 9.6 vs. 21.6 ± 10.8, respectively, p = 0.930). Magnesium supplementation significantly reduced the mild/moderate stress subgroup (DASS-42 stress score: 22.1 ± 2.8 to 12.3 ± 7.0 in magnesium vs. 21.9 ± 11.9 to 22.9 ± 11.9 in placebo, p = 0.003). Pain severity diminished significantly (p = 0.029) with magnesium while the other parameters were not significantly different between both groups. These findings show, for the first time, that magnesium improves mild/moderate stress and reduces the pain experience in fibromyalgia patients. This suggests that daily magnesium could be a useful treatment to improve the burden of disease of fibromyalgia patients and calls for a larger clinical trial.

Management of Pain Using Magnesium Sulphate: A Narrative Review

Article

Jan 2022
POSTGRAD MED

Abstract Pain is one of the most complex and unpleasant sensory and emotional human experiences. Pain relief continues to be a major medical challenge. The application of systemic opioid and regional analgesia techniques has facilitated a decrease in the occurrence and gravity of pain. Magnesium has an evolving role in pain management. Magnesium sulphate (MgSO4), the pharmacological form of magnesium, is a physiological voltage-dependent blocker of N-methyl-D-aspartate (NMDA)-coupled channels. In terms of its antinociceptive role, magnesium blocks calcium influx, which inhibits central sensitization and decreases preexisting pain hypersensitivity. These properties have encouraged the research of magnesium as an adjuvant agent for intra- and post-operative analgesia. Moreover, the mentioned magnesium impacts are also detected in patients with neuropathic pain. Intravenous magnesium sulphate, followed by a balanced analgesia, decreases opioid consumption. This review has focused on the existing evidence concerning the role of magnesium sulphate in pain management in situations including neuropathic pain, postherpetic neuralgia, trigeminal neuralgia, migraine, and post-operative pain. Additional studies are required to improve the use of magnesium sulphate for pain to increase the quality of life of patients.

Dosagem do magnésio eritrocitário: Qual é o seu real valor?

Article

Full-text available

Oct 2021

O magnésio é um cátion de localização predominantemente intracelular e de grande importância em várias funções metabólicas. É possível que tenha uma participação importante em processos álgicos e inflamatórios. Sua dosagem sérica possivelmente não representa a realidade de sua concentração corporal. A mensuração do magnésio eritrocitário talvez possa representar um avanço na sua melhor avaliação. Palavras-chave: Magnésio eritrocitário; Dor; Inflamação; Osteoartrite; Artrite Reumatoide. RESUMO Measurement of erythrocyte magnesium: What is its real value? Magnesium is a cation with location predominantly intracellular and of great importance in several metabolic functions. It is possible that it plays an important role in pain and inflammatory processes. It's serum dosage possibly does not represent the reality of it's body concentration. The measurement of erythrocyte magnesium may represent an advance in its better evaluation. ABSTRACT Revista Médica de Minas Gerais

Magnesium for Pain Treatment in 2021? State of the Art

Article

Full-text available

Apr 2021

Background: Magnesium (Mg) is commonly used in clinical practice for acute and chronic pain and has been reported to reduce pain intensity and analgesics consumption in a number of studies. Results are, however, contested. Objectives: This review aims to investigate randomised clinical trials (RCTs) on the effectiveness of Mg treatment on pain and analgesics consumption in situations including post-operative pain, migraine, renal pain, chronic pain, neuropathic pain and fibromyalgia. Results: The literature search identified 81 RCTs (n = 5447 patients) on Mg treatment in pain (50 RCTs in post-operative pain, 18 RCTs in migraine, 5 RCTs in renal pain, 6 RCTs in chronic/neuropathic pain, 2 RCTs in fibromyalgia). Conclusion: The level of evidence for the efficacy of Mg in reducing pain and analgesics consumption is globally modest and studies are not very numerous in chronic pain. A number of gaps have been identified in the literature that need to be addressed especially in methodology, rheumatic disease, and cancer. Additional clinical trials are needed to achieve a sufficient level of evidence and to better optimize the use of Mg for pain and pain comorbidities in order to improve the quality of life of patients who are in pain.

Possible prospects for using modern magnesium preparations for increasing stress resistance during COVID-19 pandemic

Article

Full-text available

Dec 2020

Introduction : The relevance of the issue of increasing stress resistance is due to a significant deterioration in the mental health of the population caused by the special conditions of the disease control and prevention during the COVID-19 pandemic. Recently, the decisive role in the severity of clinico-physiological manifestations of maladjustment to stress is assigned to magnesium ions. The aim of the work was to study the magnesium importance in the body coping mechanisms under stress for the pathogenetic substantiation of the magnesium correction in an unfavorable situation of disease control and prevention during the COVID-19 pandemic. Materials and methods : The theoretical basis of this scientific and analytical review was an analysis of modern Russian and foreign literature data posted on the electronic portals MEDLINE, PubMed-NCBI, Scientific Electronic Library eLIBRARY.RU, Google Academy, and CyberLeninka. Results and discussion : It was shown that the total magnesium level in the body plays the indicator role of the body functional reserves. Acute and chronic stresses significantly increase the magnesium consumption and cause a decrease in its body content. Magnesium deficiency is one of the main pathogenetic mechanisms of reducing stress resistance and adaptive body reserves. Arising during the COVID-19 pandemic, increased nervous and emotional tension, the lack of emotional comfort and balance can lead to the onset or deterioration of magnesium deficiency, which manifests itself in mental burnout and depletion of adaptive capacities. The inability to synthesize magnesium in the body necessitates including foodstuffs high in magnesium in the population diet during this period. The appointment of magnesium preparations is pathogenetically justified with moderate and severe magnesium deficiency. This therapy should take into account the major concomitant diseases, severity of magnesium deficiency, and a patient’s age. Conclusion : magnesium correction, carried out during the COVID-19 pandemic, will contribute to increasing stress resistance, preventing mental diseases and improving the population’s life quality.

Magnesium sulfate in oxidative stress-associated pathologies: clinical, cellular, and molecular perspectives

Article

Mar 2025

Magnesium sulfate (MgSO₄) is a therapeutically versatile agent used across various medical conditions. This review integrates experimental and computational findings to elucidate the clinical, cellular, molecular, and electronic mechanisms underlying MgSO₄’s therapeutic effects, focusing on its antioxidant properties. MgSO₄ remains the gold standard treatment for preeclampsia and eclampsia, preventing seizures and mitigating oxidative damage. In preterm birth, it offers fetal neuroprotection, although its efficacy as a tocolytic agent is limited. MgSO₄ also shows promise in treating respiratory conditions, notably severe asthma, where it acts as a bronchodilator. Its applications extend to anesthesia, pain management, and cardiac arrhythmias, reflecting its diverse pharmacological actions. Advanced computational methods, including molecular dynamics simulations and quantum chemistry calculations, have revealed how MgSO₄ interacts with cell membranes and neutralizes hydroxyl radicals. These studies suggest that MgSO₄’s antioxidant effects stem from its ability to stabilize membrane structures and modulate electron transfer processes. The therapeutic effects are mediated through multiple pathways, including calcium channel modulation, NMDA receptor antagonism, and anti-inflammatory mechanisms. Although generally safe, MgSO₄ requires careful monitoring due to its narrow therapeutic window. Future research should focus on precision dosing strategies, innovative delivery systems, and expanded therapeutic applications. A comprehensive understanding of MgSO₄’s molecular mechanisms and clinical applications will further optimize its therapeutic use.

Evaluating Magnesium Sulfate for Labor Pain Management in Primiparous Women

Article

Full-text available

Oct 2024

Effects of a synergic interaction between magnesium sulphate and ketamine on the perioperative nociception in dogs undergoing tibial plateau leveling osteotomy: a pilot study

Article

Full-text available

Oct 2024

Introduction Magnesium Sulphate (MgSO4) is commonly used in human medicine for the management of perioperative pain in different types of procedures. However, in veterinary medicine, the use of MgSO4 has not been evaluated for its analgesic efficacy in dogs, which has generated conflicts of opinion in this area of veterinary anesthesiology. The aim of this study was to evaluate the perioperative analgesic efficacy of MgSO4 in combination with Ketamine in dogs undergoing Tibial Plateau Leveling Osteotomy (TPLO). Our hypothesis is that MgSO4 plus ketamine have a synergistic action in the management of intra-and postoperative pain. Methods Twenty adult mixed breed dogs with average age 5.9 ± 2.6 years and weight 27.8 ± 9.2 kg were included in this prospective, clinical, randomized study. Dogs were randomly assigned to two groups. The MK group received ketamine (0.5 mg/kg as starting bolus followed by continuous infusion rate at 1 mg/kg/h). At the end of the ketamine bolus, MgSO4 (50 mg/kg over 15 min) was administered by the same route, followed by a constant rate infusion (CRI) at 15 mg/kg/h, IV. K group received a bolus of ketamine followed by a CRI at the same dosage described in MK group. Main cardiorespiratory parameters were recorded 10 min before the start of surgery (BASE), after the ketamine bolus (T1) and the MgSO4 bolus (T2), during the skin incision (SKIN), the osteotomy (OSTEOTOMY) and skin suturing (SUTURE). In the postoperative period, the short form of Glasgow Composite Pain scale (SF-CMPS) was used to assess pain at 30, 60, 120, and 180 min after extubation (Post30, Post60, Post120, and Post180, respectively). The main blood electrolytes (Mg²⁺, Ca²⁺, Na⁺, K⁺) were analyzed at BASE, T2, OSTEOTOMY, SUTURE and T3 (one hour after stopping MgSO4 infusion). Number of rescue analgesia and administration times were recorded both in the intra-and postoperative period. Results In K group 7 out of 10 dogs required intraoperatory rescue analgesia compared to MK group (3/10). Furthermore, mean arterial pressure (MAP) and heart rate (HR) were significantly higher at OSTEOTOMY compared to BASE time in both groups. In the postoperative period, at T120, ICMPS-SF score was higher in K group than MK group. Conclusion The administration of MgSO4 could guarantee better analgesia in the perioperative period in dogs undergoing TPLO, performing a synergistic action with ketamine.

Magnesium sulfate enhances the effect of the peripheral analgesic cocktail in total knee arthroplasty: a systematic review and meta-analysis of randomized controlled trials

Article

Full-text available

Sep 2024

Purpose Although magnesium sulfate (MgSO 4 ) is widely used as an analgesic adjuvant to peripheral analgesic cocktails, its efficacy in total knee arthroplasty (TKA) is still controversial. Therefore, we systematically reviewed and meta-analyzed the literature to assess the analgesic efficacy of MgSO 4 as an adjuvant to the analgesic cocktail in TKA. Methods The PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched. The meta-analysis was performed according to the PRISMA guidelines. Data were qualitatively synthesized or meta-analyzed using a random-effects model. Results Five randomized controlled trials involving 432 patients were included. Meta-analyses detected significant differences between the MgSO 4 and control groups in the visual analog scale (VAS) pain scores (rest) at 6, 12, and 24 h postoperatively; VAS pain scores (motion) at 12, 24, and 48 h postoperatively; morphine consumption within 24 h, 24–48 h, and during the total hospitalization period; time to first rescue analgesia after TKA; and length of hospital stay. Regarding the functional recovery, the meta-analysis demonstrated significant differences between groups in terms of knee range of motion on postoperative day 1; daily mobilization distance on postoperative day 1; and daily mobilization distance. There was no significant intergroup difference in surgical complications. Conclusion The findings suggest that MgSO 4 is a promising adjunct to the analgesic cocktail, achieving significant improvements in pain scores and total opioid consumption during the early postoperative period after TKA.

Systematic Reviews and Meta-analyses in Regional Anesthesia and Pain Medicine (Part II): Guidelines for Performing the Systematic Review

Article

Nov 2023

Transdermal Magnesium for the Treatment of Peripheral Neuropathy in Chronic Kidney Disease: A Single-Arm, Open-Label Pilot Study

Article

Jul 2023
J PALLIAT MED

Introduction: Peripheral neuropathy is common in chronic kidney disease (CKD) and may be multifactorial in origin, resulting from uremia, hyperkalemia, and diabetes. Previous studies have suggested that magnesium plays a crucial role in chronic pain. Studies evaluating magnesium in neuropathy have demonstrated mixed results. Aims: To provide preliminary data on the effectiveness of transdermal magnesium in treating peripheral neuropathy related to CKD. Methods: Twenty participants with advanced CKD were enrolled from a major teaching hospital clinic in Sydney, Australia. Each participant was provided with a spray bottle containing magnesium chloride and instructed to apply five sprays to each limb affected by neuropathy daily for 12 weeks. Participants completed the Neuropathy Total Symptom Score-6 (NTSS-6) every 4 weeks during follow-up. Serum magnesium concentrations were measured at 4-week intervals. Results: Twenty participants were recruited, of which 14 completed the 12-week follow-up period. Mean age was 78.90 years, 80.00% were female and mean estimated glomerular filtration rate was 9.78 mL/min/1.73 m2. With intention to treat analysis (mean [95% confidence interval]), NTSS-6 was significantly reduced at weeks 8 (4.04 [2.43-5.65]) and 12 (4.26 [2.47-6.05]), compared with baseline (6.92 [5.29-8.55]), p < 0.05. Serum magnesium concentration did not change significantly during the study. Conclusion: This pilot study suggests that transdermal magnesium may be beneficial in reducing frequency and severity of peripheral neuropathic symptoms in patients with advanced CKD. Trial Registration: australianclinicaltrials.gov.au. Identifier: ACTRN12621000841875. Date first registered January 7, 2021.

Role of Smooth Muscle Cells Regulated by Vitamin D in Bronchial Asthma Airway Remodeling and Efficacy of Nanomedicine on Bronchial Asthma

Article

Jul 2022
J BIOMED NANOTECHNOL

This study aimed to analyze the therapeutic effect of nanomedicine on bronchial asthma and the effect of vitamin 1,25-(OH) 2 D 3 on airway remodeling. The four groups of Z1 (1,25-(OH) 2 D 3 +RNPEG-ABT-199), Z2 (RNPEG-ABT-199), Z3 (ABT-199), and Z4 (normal Control) were designed in this study. The prepared acid-responsive mitochondrial targeting nanomedicine (RNPEG-ABT-199) and non-responsive mitochondrial targeting nanomedicine (PEG-ABT-199) were applied to the treatment of asthma mouse models. The results showed the PU value of caspase-3 in Z4 was lower than Z1, Z2, and Z3 groups; and in Z3 was higher than Z1 and Z2 groups. IL-4, IL-5, and TNF- α levels in Z3 were obviously higher than Z1, Z2, and Z4 groups, while those in the Z1 were obviously lower than the Z2 and Z4 groups; the proliferation activity of airway smooth muscle cells (ASMCs) of Z3 was obviously higher than the Z1, Z2, and Z4 groups, and that of the Z1 was obviously lower than the Z2 group. In short, RNPEG-ABT-199 has stronger lysosomal escape ability and mitochondrial targeting than PEG-ABT-199. RNPEG-ABT-199 can cause apoptosis of inflammatory cells and decrease pro-inflammatory cytokines, which is better than PEG-ABT-199. Vitamin1,25-(OH) 2 D 3 can obviously inhibit the proliferation activity of ASMCs cells, and be used in the treatment of asthma along with RNPEG-ABT-199.

Electroacupuncture alleviates the transition from acute to chronic pain through the p38 MAPK/TNF-α signalling pathway in the spinal dorsal horn

Article

Jul 2021

Background Hyperalgesic priming (HP) is a model of the transition from acute to chronic pain. Electroacupuncture (EA) could inhibit pain development through the peripheral dorsal root ganglia; however, it is unclear whether it can mitigate the transition from acute to chronic pain by attenuating protein expression in the p38 MAPK (mitogen-activated protein kinase)/tumour necrosis factor alpha (TNF-α) pathway in the spinal dorsal horn. Aims We aimed to determine whether EA could prevent the transition from acute to chronic pain by affecting the p38 MAPK/TNF-α pathway in the spinal dorsal horn in a rat model established using HP. Methods We first randomly subdivided 30 male Sprague-Dawley (SD) rats into 5 groups ( n = 6 per group): control (N), sham HP (Sham-HP), HP, HP + SB203580p38 MAPK (HP+SB203580), and HP + Lenalidomide (CC-5013) (HP+Lenalidomide). We then randomly subdivided a further 30 male SD rats into 5 groups ( n = 6 per group): Sham-HP, HP, sham EA (Sham EA), EA (EA), and EA + U-46619 p38 MAPK agonist (EA+U-46619). We assessed the effects of EA on the mechanical paw withdrawal threshold and p38 MAPK/TNF-α expression in the spinal dorsal horn of rats subjected to chronic inflammatory pain. Results Rats in the EA group had reduced p38 MAPK and TNF-α expression and had significantly reduced mechanical hyperalgesia compared with rats in the other groups. Conclusion Our findings indicate that EA could increase the mechanical pain threshold in rats and inhibit the transition from acute pain to chronic pain. This mechanism could involve reduced p38 MAPK/TNF-α expression in the spinal dorsal horn.

Food for Special Medical Purposes and Nutraceuticals for Pain: A Narrative Review

Article

Full-text available

Feb 2021

Introduction: The present paper focuses on the possible contribution of food compounds to alleviate symptomatic pains. Chronic pain can more easily be linked to anticipatory signals such as thirst and hunger than it is to sensory perceptions as its chronicity makes it fall under the behavioural category rather than it does senses. In fact, pain often negatively affects one's normal feeding behavioural patterns, both directly and indirectly, as it is associated with pain or because of its prostrating effects. Nutritional compounds for pain: Several nutraceuticals and Foods for Special Medical Purposes (FSMPs) are reported to have significant pain relief efficacy with multiple antioxidant and anti-inflammatory properties. Apart from the aforementioned properties, amino acids, fatty acids, trace elements and vitamins may have a role in the modulation of pain signals to and within the nervous system. Conclusion: In our opinion, this review could be of great interest to clinicians, as it offers a complementary perspective in the management of pain. Trials with well-defined patient and symptoms selection and a robust pharmacological design are pivotal points to let these promising compounds become better accepted by the medical community.

Magnesium Citrate Increases Pain Threshold and Reduces TLR4 Concentration in the Brain

Article

Full-text available

May 2021
BIOL TRACE ELEM RES

Magnesium is being investigated in various clinical conditions and has shown to be effective in some chronic pain models. However, it is not clear if oral magnesium use affects pain perception in acute pain. TLR4’s (toll-like receptor) role in pain perception has emerged through its role in immune pathways and ion channels. The aim of this study is to investigate the effect of a single oral dose of magnesium citrate on pain conduction and whether with magnesium, the expression of TLR4 changes in the acute phase. Following a single dose of 66-mg/kg magnesium citrate administration to male Balb-c mice, pain perception (via hot-plate test), motor conduction (via electrophysiological recording, forelimb grip strength, rotarod and open-field tests), and emotional state (via elevated plus maze and forced swim test) were evaluated. In behavioral experiments, the control group was compared with applied magnesium for three different time groups (4, 8, 24 h). TLR4 expression was measured in four groups: control, magnesium (Mg), hot plate (HP), and Mg + HP. Hot plate latency was prolonged in the magnesium group (p < 0.0001) and electrophysiological recordings (p < 0.001) and forelimb grip strength measurement (p < 0.001) determined motor latency. Compared with the untreated hot plate group, TLR4 levels was lower in the brain (p = 0.023) and higher in the sciatic nerve (p = 0.001) in the magnesium-treated hot plate group. Consequently, the study indicated a single dose of magnesium citrate appeared to cause weakening in the transmission and perception of nociceptive pain. TLR4 may act as a regulator in magnesium’s effects on pain perception.

Systematic Review in Clinical Research

Article

Sep 2020
ANESTH ANALG

Perioperative systemic magnesium sulphate to minimize acute and chronic post-thoracotomy pain: A prospective observational study

Article

Full-text available

Feb 2019

Background: Thoracotomy leads to acute and chronic post-thoracotomy pain (CPTP). The purpose of this study was to investigate the effect of magnesium sulphate (MgSO4) administered perioperatively on acute postoperative and CPTP syndrome. Methods: One hundred patients were enrolled in this prospective, observational study. Analgesic medication was provided according to the World Health Organization pain relief ladder (control group). The study group received additionally MgSO4 (40 mg/kg over 10 minutes) during induction of anesthesia followed by an infusion over 24 hours (10 mg/kg/h). The presence and severity of pain were assessed before surgery, on postsurgical days 1-8, 30 and 90, respectively. The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) was used pre- and postoperatively for documentation of neuropathic pain. The incidence and severity of CPTP were assessed by a telephone survey 30 and 90 days after surgery. Results: Numerical rating scale (NRS) pain scores at rest were significantly lower in the study group receiving MgSO4 at days 1 to 8 (P<0.05). Thirty days after surgery, 2.1% of the MgSO4-patients had a LANSS score ≥12 compared to 14.3% in the control group (P=0.031). No patient had a LANSS score ≥12 in the study group compared to the control group (0% vs. 12.2%, P<0.05) 90 days following surgery. Conclusions: MgSO4 administration reduces postoperative pain at rest according to the NRS pain scores and is effective in preventing chronic neuropathic post-thoracotomy pain measured by LANSS score. Prospective-randomized trials are needed to confirm the results of the present study.

Magnesium for the management of chronic non-cancer pain in adults: A systematic review protocol (Preprint)

Article

Full-text available

Jul 2018

Background Chronic pain is a highly prevalent and complex health problem that is associated with a severe symptom burden, as well as substantial economic and social impact. Many patients with chronic pain still suffer from unrelieved or undertreated pain due to the incomplete efficacy and dose-limiting adverse effects of current therapies. Long-term and high-dose opioid use has considerably increased in the past 20 years despite limited evidence supporting its effectiveness in several chronic pain conditions, and serious concerns have emerged regarding adverse effects and potential misuse. Until recently, the steady increase in opioid prescribing rates has been associated with rising opioid-related mortality and other serious problems, emphasizing the need for better nonopioid therapies. Emerging evidence supports the safe use of magnesium in controlling chronic pain, but its overall efficacy and safety is still unclear. Objective This paper aims to assess the efficacy and safety of magnesium compared with a placebo for the treatment of chronic noncancer pain. Methods We will conduct a detailed search on Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE from their inception until the date the searches are run to identify relevant randomized controlled trials. The reference lists of retrieved studies as well as Web-based trial registries will also be searched. We will include randomized double-blind trials comparing magnesium (at any dose, frequency, or route of administration) with placebo using participant-reported pain assessment. Two reviewers will independently evaluate studies for eligibility, extract data, and assess trial quality and potential bias. Risk of bias will be assessed using criteria outlined in the Cochrane Handbook for Systematic Review of Interventions. Primary outcomes for this review will include any validated measure of pain intensity or pain relief. Dichotomous data will be used to calculate the risk ratio and number needed to treat or harm. The quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. Results This protocol is grant-funded and has undergone a peer-review process through the Queen’s University Department of Anesthesiology and Perioperative Medicine Vandewater Endowed Studentship. This project is also supported, in part, by the Chronic Pain Network of the Canadian Institutes of Health Research Strategy for Patient-Oriented Research. The electronic database search strategies are currently being developed and modified. The entire review is expected to be completed by January 1, 2019. Conclusions The completion of this review is expected to identify available high-quality evidence describing the efficacy and safety of magnesium for the treatment of chronic noncancer pain. International Registered Report Identifier (IRRID) PRR1-10.2196/11654

Preventive effect of oral magnesium in postmastectomy pain: Protocol for a randomised, double-blind, controlled clinical trial

Article

Full-text available

Sep 2018

Introduction Breast cancer affects 1 in 10 women worldwide, and mastectomy is a cause of chronic pain with neuropathic characteristics. N -methyl-D-aspartate receptor (NMDAR) antagonists such as ketamine, memantine, dextromethorphan or magnesium are used to treat refractory pain by blocking NMDAR. Oral memantine has been shown to prevent postmastectomy pain and cognitive impact and to maintain quality of life. Likewise, the present study is intended to assess the preventive effect of oral magnesium, administered ahead of mastectomy, on the development of neuropathic pain. As a physiological blocker of NMDAR, magnesium could be an interesting candidate to prevent postoperative pain and associated comorbidities, including cognitive and emotional disorders, multiple analgesic consumption and impaired quality of life. Methods and analysis A randomised double-blind controlled clinical trial ( NCT03063931 ) will include 100 women with breast cancer undergoing mastectomy at the Oncology Hospital, Clermont-Ferrand, France. Magnesium (100 mg/day; n=50) or placebo (n=50) will be administered for 6 weeks, starting 2 weeks before surgery. Intensity of pain, cognitive and emotional function and quality of life will be assessed by questionnaires. The primary endpoint is pain intensity on a 0–10 numerical rating scale at 1 month postmastectomy. Data analysis will use mixed models; all tests will be two-tailed, with type-I error set at α=0.05. Ethics and dissemination The study protocol and informed consent form were approved in December 2016 by the French Research Ethics Committee (South East VI Committee). Results will be communicated in various congresses and published in international publications. Trial registration number NCT03063931 .

The Role of Magnesium in Neurological Disorders

Article

Full-text available

Jun 2018

Magnesium is well known for its diverse actions within the human body. From a neurological standpoint, magnesium plays an essential role in nerve transmission and neuromuscular conduction. It also functions in a protective role against excessive excitation that can lead to neuronal cell death (excitotoxicity), and has been implicated in multiple neurological disorders. Due to these important functions within the nervous system, magnesium is a mineral of intense interest for the potential prevention and treatment of neurological disorders. Current literature is reviewed for migraine, chronic pain, epilepsy, Alzheimer’s, Parkinson’s, and stroke, as well as the commonly comorbid conditions of anxiety and depression. Previous reviews and meta-analyses are used to set the scene for magnesium research across neurological conditions, while current research is reviewed in greater detail to update the literature and demonstrate the progress (or lack thereof) in the field. There is strong data to suggest a role for magnesium in migraine and depression, and emerging data to suggest a protective effect of magnesium for chronic pain, anxiety, and stroke. More research is needed on magnesium as an adjunct treatment in epilepsy, and to further clarify its role in Alzheimer’s and Parkinson’s. Overall, the mechanistic attributes of magnesium in neurological diseases connote the macromineral as a potential target for neurological disease prevention and treatment.

Effect of ketamine combined with magnesium sulfate in neuropathic pain patients (KETAPAIN): Study protocol for a randomized controlled trial

Article

Full-text available

Nov 2017
TRIALS

Background Neuropathic pain is difficult to treat, and the efficacy of recommended drugs remains limited. N-methyl-d-aspartate receptors are implicated, and antagonists are a pharmacological option. Ketamine is widely used in French pain clinics, but without consensus or recommendations. Furthermore, the association of ketamine with magnesium has been poorly studied. The aim of the present study is to evaluate the benefit of ketamine with or without magnesium in refractory neuropathic pain. Methods/design A randomized, double-blind, crossover, placebo-controlled study will be performed in Clermont-Ferrand University Hospital, Clermont-Ferrand, France. The aim is to evaluate the effect of ketamine with or without magnesium in 22 patients with neuropathic pain. Intravenous ketamine/placebo, ketamine/magnesium sulfate, or placebo/placebo will be administered consecutively to each patient, in random order, once at 5-week intervals. The primary endpoint is the AUC of pain intensity assessed on a 0–10 Numeric Pain Rating Scale for a 5-week period. Data analysis will be performed on an intention-to-treat basis, and all statistical tests (except primary analysis) will be performed with an α risk of 5% (two-sided). Discussion Considering the poor efficacy of the drugs available for neuropathic pain, ketamine with or without magnesium sulfate may be a valuable therapeutic option that needs to be standardized. Trial registration EudraCT number–2015-000142-29. Registered on April 9, 2015; version 1.4 Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2254-3) contains supplementary material, which is available to authorized users.

Intestinal Absorption and Factors Influencing Bioavailability of Magnesium- An Update

Article

Full-text available

Sep 2017
Curr Nutr Food Sci

Background Information on the bioavailability of the essential mineral Mg2+ is sparse. Objective/Method Evaluation of the present knowledge on factors influencing the bioavailability and intestinal absorption of Mg2+. Results Mg2+ is absorbed via a paracellular passive and a transcellular active pathway that involves TRPM6/7 channel proteins. The bioavailability of Mg2+ varies within a broad range, depending on the dose, the food matrix, and enhancing and inhibiting factors. Dietary factors impairing Mg2+ up-take include high doses of other minerals, partly fermentable fibres (e.g., hemicellulose), non-fermentable fibres (e.g., cellulose, lignin), phytate and oxalate, whereas proteins, medium-chain-triglycerides, and low- or indigestible carbohydrates (e.g., resistant starch, oligosaccharides, inulin, mannitol and lactulose) enhance Mg2+ uptake. The Mg2+ dose is a major factor controlling the amount of Mg2+ absorbed. In principle, the relative Mg2+ uptake is higher when the mineral is in-gested in multiple low doses throughout the day compared to a single, large intake of Mg2+. The type of Mg2+ salt appears less relevant than is often thought. Some studies demonstrated a slightly higher bioavailability of organic Mg2+ salts compared to inorganic compounds under standardized conditions, whereas other studies did not. Conclusion Due to the lack of standardized tests to assess Mg2+ status and intestinal absorption, it remains unclear which Mg2+ binding form produces the highest bioavailability. The Mg2+ intake dose combined with the endogenous Mg2+ status is more important. Because Mg2+ cannot be stored but only retained for current needs, a higher absorption is usually followed by a higher excretion of the mineral.

A Systematic Review of NMDA Receptor Antagonists for Treatment of Neuropathic Pain in Clinical Practice

Article

Full-text available

Sep 2017

Objective: To investigate the efficacy of N-methyl-D-aspartate receptor (NMDA) receptor antagonists for neuropathic pain and review literature to determine if specific pharmacologic agents provide adequate neuropathic pain relief. Methods: Literature was reviewed on PubMed using a variety of key words for 8 NMDA receptor antagonists. These key words include: "Ketamine and Neuropathy", "Ketamine and Neuropathic Pain", "Methadone and Neuropathy", "Methadone and Neuropathic Pain", "Memantine and Neuropathic pain", "Memantine and Neuropathy", "Amantadine and Neuropathic Pain", "Amantadine and Neuropathy", "Dextromethorphan and Neuropathic Pain", "Dextromethorphan and Neuropathy", "Carbamazepine and Neuropathic Pain", "Carbamazepine and Neuropathy", "Valproic Acid and Neuropathy", "Valproic Acid and Neuropathic Pain", "Phenytoin and Neuropathy" and "Phenytoin and Neuropathic Pain". With the results, the papers were reviewed using the PRISMA (Preferred Reporting in Systematic and Meta-Analyses) guideline. Results: A total of 58 randomized controlled trials were reviewed among 8 pharmacologic agents, which are organized by date and alphabetical order. Of the trials for ketamine, 15 showed some benefit for analgesia. Methadone had 3 beneficiary trials, while amantadine and memantine each only had 2 trials showing neuropathic analgesic properties. Dextromethorphan and Valproic Acid both had 4 randomized controlled trials that showed some neuropathic treatment benefit while carbamazepine had over 8 trials showing efficacy. Finally, phenytoin only had 1 trial that showed clinical response in treatment. Conclusion: It is evident there are a variety of NMDA receptor antagonist agents that should be considered for treatment of neuropathic pain. Nevertheless, continued and further investigation of the 8 pharmacologic agents is needed to continue to evaluate their efficacy for treatment of neuropathic pain.

Effects of systemic lidocaine versus magnesium administration on postoperative functional recovery and chronic pain in patients undergoing breast cancer surgery: A prospective, randomized, double-blind, comparative clinical trial

Article

Full-text available

Mar 2017
PLOS ONE

Introduction We aimed to compare the effects of intraoperative lidocaine and magnesium on postoperative functional recovery and chronic pain after mastectomy due to breast cancer. Systemic lidocaine and magnesium reduce pain hypersensitivity to surgical stimuli; however, their effects after mastectomy have not been evaluated clearly. Methods In this prospective, double-blind, clinical trial, 126 female patients undergoing mastectomy were randomly assigned to lidocaine (L), magnesium (M), and control (C) groups. Lidocaine and magnesium were administered at 2 mg/kg and 20 mg/kg for 15 minutes immediately after induction, followed by infusions of 2 mg/kg/h and 20 mg/kg/h, respectively. The control group received the same volume of saline. Patient characteristics, perioperative parameters, and postoperative recovery profiles, including the Quality of Recovery 40 (QoR-40) survey, pain scales, length of hospital stay, and the short-form McGill pain questionnaire (SF-MPQ) at postoperative 1 month and 3 months were evaluated. Results The global QoR-40 scores on postoperative day 1 were significantly higher in group L than in group C (P = 0.003). Moreover, in sub-scores of the QoR-40 dimensions, emotional state and pain scores were significantly higher in group L than those in groups M and C (P = 0.027 and 0.023, respectively). At postoperative 3 months, SF-MPQ and SF-MPQ-sensitive scores were significantly lower in group L than in group C (P = 0.046 and 0.036, respectively). Conclusions Intraoperative infusion of lidocaine improved the quality of recovery and attenuated the intensity of chronic pain in patients undergoing breast cancer surgery.

Higher bioavailability of magnesium citrate as compared to magnesium oxide shown by evaluation of urinary excretion and serum levels after single-dose administration in a randomized cross-over study

Article

Full-text available

Jan 2017

Background The development of several disorders, such as cardiovascular diseases, diabetes and osteoporosis, has been linked to suboptimal dietary magnesium (Mg) intake. In this context, a number of studies have tried to investigate which Mg compounds are best suited for Mg supplementation. Results suggest that organic Mg compounds are superior to the inorganic Mg oxide in terms of bioavailability, but a reliable statement cannot yet be made due to systematic differences in the applied study designs. Methods This single-center, randomized, open, 2-period, 2-supplementation, 2-sequence, single-dose, cross-over study was conducted in 20 healthy male subjects of Caucasian origin to investigate and compare the bioavailability of Mg citrate, an organic Mg compound, and Mg oxide, an inorganic Mg compound. In order to reliably assess the bioavailability of both Mg compounds, subjects were supplemented with magnesium to saturate their Mg-pools before administration of each study product. The bioavailability of both Mg compounds was then assessed by measurement of the renally eliminated Mg quantity during an interval of 24 h after single-dose Mg administration (Ae 0-24h) as primary endpoint. Additionally, the Mg concentrations in a subset of leukocytes, in erythrocytes and in serum were measured on an exploratory basis. Results After administration, Ae 0-24h of magnesium was higher for Mg citrate than for Mg oxide. Ae 0-24h for both study products was compared by analysis of variance (ANOVA), revealing an adjusted mean difference of 0.565 mmol, which was statistically significant at the 5% level (95% confidence interval of 0.212 to 0.918 mmol, p = 0.0034). Besides, serum Mg concentrations were statistically significantly higher for Mg citrate than for Mg oxide at several time points after administration. No statistically significant difference was shown in intracellular Mg contents. Conclusions This study confirms former study results showing a higher bioavailability of the organic Mg compound Mg citrate compared to Mg oxide. It can be concluded that Mg citrate, similar to other organic Mg compounds, may be more suitable than Mg oxide to optimize the dietary magnesium intake. Trial registration Retrospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615001268538) on November 19, 2015. Keywords Bioavailability Oral Mg supplementation Mg citrate Mg oxide Urinary excretion

Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement

Article

Full-text available

Jan 2014

Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.

Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: A randomized, placebo-controlled, double-blind, multicenter trial

Article

Full-text available

Dec 2015
J HEADACHE PAIN

Non-medical, non-pharmacological and pharmacological treatments are recommended for the prevention of migraine. The purpose of this randomized double-blind placebo controlled, multicenter trial was to evaluate the efficacy of a proprietary nutritional supplement containing a fixed combination of magnesium, riboflavin and Q10 as prophylactic treatment for migraine. 130 adult migraineurs (age 18 - 65 years) with ≥ three migraine attacks per month were randomized into two treatment groups: dietary supplementation or placebo in a double-blind fashion. The treatment period was 3 months following a 4 week baseline period without prophylactic treatment. Patients were assessed before randomization and at the end of the 3-month-treatment-phase for days with migraine, migraine pain, burden of disease (HIT-6) and subjective evaluation of efficacy. Migraine days per month declined from 6.2 days during the baseline period to 4.4 days at the end of the treatment with the supplement and from 6.2.days to 5.2 days in the placebo group (p = 0.23 compared to placebo). The intensity of migraine pain was significantly reduced in the supplement group compared to placebo (p = 0.03). The sum score of the HIT-6 questionnaire was reduced by 4.8 points from 61.9 to 57.1 compared to 2 points in the placebo-group (p = 0.01). The evaluation of efficacy by the patient was better in the supplementation group compared to placebo (p = 0.01). Treatment with a proprietary supplement containing magnesium, riboflavin and Q10 (Migravent® in Germany, Dolovent® in USA) had an impact on migraine frequency which showed a trend towards statistical significance. Migraine symptoms and burden of disease, however, were statistically significantly reduced compared to placebo in patients with migraine attacks.

Magnesium: A versatile drug for anesthesiologists

Article

Full-text available

Jul 2013

Sang-Hwan Do

Magnesium sulfate has been used in preeclampsia patients in order to prevent seizure. It is also used for the treatment of arrhythmia and asthma and as an anesthetic adjunct in patients undergoing surgery for pheochromocytoma. However, its potentiating effects on perioperative analgesia and muscle relaxation have drawn attention recently. These characteristics of magnesium (anesthetic- and analgesic-sparing effect) enable anesthesiologists to reduce the use of anesthetics during surgery and the use of analgesics after surgery. Magnesium sulfate has a high therapeutic index and cost-effectiveness. Considering these diverse characteristics useful for anesthesia, appropriate use of magnesium sulfate would improve surgical outcome and patients' satisfaction.

A double-blinded randomised controlled study of the value of sequential intravenous and oral magnesium therapy in patients with chronic low back pain with a neuropathic component

Article

Full-text available

Mar 2013
ANAESTHESIA

Persistent mechanical irritation of the nerve root sets up a series of events mediating sensitisation of the dorsal roots and dorsal horns in the spinal cord. Current evidence supports the role of magnesium in blocking central sensitisation through its effect on N-methyl-d-aspartate receptors. We studied the role of sequential intravenous and oral magnesium infusion in patients with chronic low back pain with a neuropathic component. We recruited a cohort of 80 patients with chronic low back pain with a Leeds Assessment of Neuropathic Signs and Symptoms pain scale score ≥ 12, who were receiving a physical therapy programme. All patients were treated with anticonvulsants, antidepressants and simple analgesics; in addition 40 patients received placebo for 6 weeks (control group), while the other 40 patients received an intravenous magnesium infusion for 2 weeks followed by oral magnesium capsules for another 4 weeks (magnesium group). Patients were asked to rate their pain using a numerical rating scale. Lumbar spine range of motion was also determined using a long-arm goniometer. In the magnesium group, the patients' numerical rating scales revealed a significant reduction in pain intensity. The mean (SD) pre-treatment value was 7.5 (2.2) compared with 4.7 (1.8) at 6 months (p = 0.034). The reduction in pain intensity was accompanied by significant improvement in lumbar spine range of motion during the follow-up period. The mean (SD) values of flexion, extension and lateral flexion movements before treatment and at 6-month follow up were 22.2 (8.4) vs 34.7 (11.5) (p = 0.018), 11.8 (3.4) vs 16.9 (3.5) (p = 0.039), 11.4 (3.6) vs 17.2 (4.4) (p = 0.035), respectively. Our findings show that a 2-week intravenous magnesium infusion followed by 4 weeks of oral magnesium supplementation can reduce pain intensity and improve lumbar spine mobility during a 6-month period in patients with refractory chronic low back pain with a neuropathic component.

Pain measures and cut-offs - no worse than mild pain as a simple, universal outcome

Article

Full-text available

Jan 2013
ANAESTHESIA

The Effects of Magnesium, L-: Carnitine, and Concurrent Magnesium-L-: Carnitine Supplementation in Migraine Prophylaxis.

Article

Full-text available

Aug 2012
BIOL TRACE ELEM RES

Given the conflicting results about the positive effects of magnesium and L-: carnitine and as there is no report concerning concurrent supplementation of magnesium and L-: carnitine on migraine prophylaxis, the effects of magnesium, L-: carnitine, and concurrent magnesium-L-: carnitine supplementation on migraine indicators were assessed. In this clinical trial, 133 migrainous patients were randomly assigned into three intervention groups: magnesium oxide (500 mg/day), L-: carnitine (500 mg/day), and Mg-L-: carnitine (500 mg/day magnesium and 500 mg/day L-: carnitine), and a control group. After 12 weeks of supplementation, the checklist of migraine indicators including migraine attacks/month, migraine days/month, and headache severity was completed, and serum concentrations of magnesium and L-: carnitine were measured by atomic absorption spectrophotometry and enzymatic UV test, respectively. The results showed a significant reduction in all migraine indicators in all studied groups (p < 0.05). The ANOVA results showed a significant reduction in migraine frequency across various supplemented and control groups (p = 0.008). By separating the effects of magnesium supplementation from other confounding factors such as routine treatments using the repeated measures and nested model, it was clarified that magnesium supplementation had a significant effect on all migraine indicators. Oral supplementation with magnesium oxide and L-: carnitine and concurrent supplementation of Mg-L-: carnitine besides routine treatments could be effective in migraine prophylaxis; however, larger trials are needed to confirm these preliminary findings.

Oral magnesium treatment in patients with neuropathic pain: A randomized clinical trial

Article

Full-text available

Jun 2011
MAGNESIUM RES

Studies in animals and in patients have suggested that magnesium (Mg), a physiological blocker of N-methyl-D-aspartate receptor, could have an antinociceptive effect in painful situations. This randomised, double-blind, controlled trial in two parallel groups aims at studying oral Mg effects in patients with neuropathic pain. It explores the impact of Mg (6x419 mg Mg chloride/capsule per day for a month), versus placebo (lactose) on pain [Neuropathic Pain Symptom Inventory (NPSI) and numerical scale (NS)], and on quality of life indicators after 4 weeks treatment, in 45 patients suffering from neuropathic pain. After 4 weeks, NPSI, NS and quality of life are not different in the Mg and placebo groups, while the frequency of pain paroxysms diminishes and the emotional component improves in the Mg group compared to baseline. This clinical trial displays a large placebo response and could not demonstrate any significant difference in pain alleviation after a month of oral treatment between Mg and placebo in patients suffering from neuropathic pain. Frequency of pain paroxysms and emotional impact will be explored in future studies as they constitute major aspects of pain alleviation in chronic pain conditions.

The Need for a Canadian Pain Strategy

Article

Full-text available

Mar 2011

Mary Ellen T Lynch

Pain is undertreated in Canada and there are major problems with access to appropriate care for all types of pain. A national pain strategy addressing educational, clinical and research needs is required. Following the recent International Pain Summit and the creation of the Declaration of Montreal, which identified that access to pain management is a fundamental human right, it is essential that Canada takes a leading role in proceeding with a national pain strategy and demonstrates to Canadians and the rest of the world that it is possible to treat our citizens with the compassion and dignity that they deserve. Following work started by the Canadian Pain Society Task Force on Service Delivery, the Canadian Pain Society and the Canadian Pain Coalition are in the process of leading a Canadian Pain Strategy and Canadian Pain Summit scheduled for spring 2012. A website will soon be available with further information about how you can get involved. Stay tuned.

Intravenous Micronutrient Therapy (Myers' Cocktail) for Fibromyalgia: A Placebo-Controlled Pilot Study

Article

Full-text available

Feb 2009
J ALTERN COMPLEM MED

Intravenous micronutrient therapy (IVMT), and specifically the Myers' Cocktail, is a popular approach for treating fibromyalgia syndrome (FMS) among complementary and alternative medicine practitioners, but its efficacy is uncertain. This trial assessed the feasibility, safety, and provided insights into the efficacy of this therapy. This was a randomized, double-blind, placebo-controlled pilot study. The study locations were an academic research center, teaching hospital, and affiliated Integrative Medicine Center in Derby, CT. The subjects were 34 adults with American College of Rheumatology (ACR)-defined FMS. Subjects were randomly assigned either to treatment (weekly infusions of IVMT) or to placebo (weekly infusions of lactated Ringer's solution) for 8 weeks. Primary outcome was change in the Tender Point Index, assessed 8 and 12 weeks after initiation. Secondary measures included a Visual Analog Scale to assess global pain, and validated measures of physical function (Fibromyalgia Impact Questionnaire), mood (Beck Depression Index), and quality of life (Health Status Questionnaire 2.0). Clinically significant improvements were noted (of a magnitude similar to other effective interventions). However, in part because of the high placebo response and the small sample size, no statistically significant differences were seen between groups, in any outcome measure, at 8 and 16 weeks. Statistically significant within-group differences were seen in both the intervention and placebo groups, demonstrating a treatment effect for both IVMT and placebo. At 8 weeks, the IVMT group experienced significantly improved tender points, pain, depression, and quality of life directly following treatment (all p < or = 0.02), while the placebo group experienced significantly improved tender points only (p < or = 0.05). The treatment effects of IVMT persisted at 4 weeks postintervention for tender points, pain, and quality of life, while placebo effects persisted only for tender points. A single minor adverse event was noted in one subject in the intervention group. This first controlled pilot study established the safety and feasibility of treating FMS with IVMT. Most subjects experienced relief as compared to baseline, but no statistically significant differences were seen between IVMT and placebo. The efficacy of IVMT for fibromyalgia, relative to placebo, is as yet uncertain.

The effects of magnesium prophylaxis in migraine without aura

Article

Full-text available

Jun 2008

There are inconsistent findings about the efficacy of magnesium in the prophylaxis of migraine attacks and there is no study of magnesium prophylaxis focused on migraine subtypes without aura. In this double blind, randomized, placebo controlled study; we tried to evaluate the prophylactic effects of oral magnesium in migraine patients without aura. The prophylactic effects of 600 mg/day oral magnesium citrate supplementation were assessed by means of clinical evaluation, visual evoked potential and statistical parametric mapping of brain single photon emission computerized tomography before and after a 3 month treatment period. The results of 30 patients with migraine without aura (20-55 years old with 2-5 migraine attacks per month) on magnesium treatment were compared with those of 10 patients with similar properties on placebo treatment. Migraine attack frequency, severity and P1 amplitude in visual evoked potential examination decreased after magnesium treatment with respect to pretreatment values (p < 0.001). In a comparison of the effects of magnesium treatment with those of placebo, post/pretreatment ratios of migraine attack frequency, severity and P1 amplitude in Mg treatment group were found to be significantly lower than those in placebo treatment group (attack frequency p = 0.005, attack severity p < 0.001, P1 amplitude p < 0.05). Cortical blood flow in inferolateral frontal (p < 0.001), inferolateral temporal (p = 0.001) and insular regions (p < 0.01) increased significantly after magnesium treatment with respect to the pretreatment; while such significant changes of cortical blood flow were not observed with placebo treatment. These results have made us think that magnesium is a beneficial agent in prophylaxis of migraine without aura and might work with both vascular and neurogenic mechanisms.

NMDA receptor blockade in chronic neuropathic pain: A comparison of ketamine and magnesium chloride

Article

Full-text available

Mar 1996

Ten patients (4 female, 6 male) aged 34-67 years suffering from peripheral neuropathic pain participated in a double-blind placebo-controlled study where ketamine or magnesium chloride were administered by a 10 min bolus infusion (ketamine: 0.84 mumol/kg = 0.2 mg/kg, magnesium: 0.16 mmol/kg) followed by a continuous infusion (ketamine: 1.3 mumol/kg/h = 0.3 mg/kg/h, magnesium: 0.16 mmol/kg/h). Ongoing pain determined by VAS score, area of touch-evoked allodynia, detection and pain thresholds to mechanical and thermal stimuli were measured before and during drug infusion. Ketamine produced a significant reduction of spontaneous pain (57%) and of the area of allodynia (33%). Magnesium chloride reduced pain (29%) and area of allodynia (18%) insignificantly. Following ketamine there was a significant correlation between the reduction in ongoing pain and reduction in area of touch-evoked allodynia. Detection and pain thresholds to mechanical and thermal stimuli were not significantly changed by the drugs. These findings suggest that both ongoing pain and touch-evoked pain (allodynia) in neuropathic pain are inter-related phenomena, which may be mediated by the same mechanism and involving a N-methyl-D-aspartate receptor.

Magnesium - An Update on Physiological, Clinical and Analytical Aspects

Article

Full-text available

May 2000
CLIN CHIM ACTA

There is an increased interest in the role of magnesium ions in clinical medicine, nutrition and physiology. The characteristics of the binding of magnesium and calcium ions to various components, macromolecules and biological membranes are described. Magnesium affects many cellular functions, including transport of potassium and calcium ions, and modulates signal transduction, energy metabolism and cell proliferation. The mechanism of cellular uptake and efflux of magnesium, its intracellular transport, intestinal absorption, renal excretion and the effect of hormones on these are reviewed. Magnesium deficiency is not uncommon among the general population: its intake has decreased over the years especially in the western world. The magnesium supplementation or intravenous infusion may be beneficial in various diseased states. Of special interest is the magnesium status in alcoholism, eclampsia, hypertension, atherosclerosis, cardiac diseases, diabetes, and asthma. The development of instrumentation for the assay of ionized magnesium is reviewed, as are the analytical procedures for total magnesium in blood and free magnesium in the cytosol. The improved procedures for the assay of different magnesium states are useful in understanding the role of magnesium in health and disease.

Bioavallability of US commercial magnesium preparations

Article

Full-text available

Jan 2002

Magnesium deficiency is seen with some frequency in the outpatient setting and requires oral repletion or maintenance therapy. The purpose of this study was to measure the bioavailability of four commercially-available preparations of magnesium, and to test the claim that organic salts are more easily absorbed. Bioavailability was measured as the increment of urinary maginesium excretion in normal volunteers given approximately 21 mEq/day of the test preparations. Results indicated relatively poor bioavailability of magnesium oxide (fractional absorption 4 per cent) but significantly higher and equivalent bioavailability of magnesium chloride, magnesium lactate and magnesium aspartate. We conclude that there is relatively poor bioavailability of magnesium oxide, but greater and equivalent bioavailability of magnesium chloride, lactate, and aspartate. Inorganic magnesium salts, depending on the preparation, may have bioavailability equivalent to organic magnesium salts.

Magnesium in the gynaecological practice: A literature review

Article

Apr 2017
MAGNESIUM RES

A growing amount of evidence suggests that magnesium deficiency may play an important role in several clinical conditions concerning women health such as premenstrual syndrome, dysmenorrhea, and postmenopausal symptoms. A number of studies highlighted a positive correlation between magnesium administration and relief or prevention of these symptoms, thus suggesting that magnesium supplementation may represent a viable treatment for these conditions. Despite this amount of evidence describing the efficacy of magnesium, few and un-systematize data are available about the pharmacological mechanism of this ion for these conditions. Herein, we review and systematize the available evidence about the use of oral magnesium supplementation in several gynecological conditions and discuss the pharmacological mechanisms that characterize these interventions. The picture that emerges indicates that magnesium supplementation is effective in the prevention of dysmenorrhea, premenstrual syndrome, and menstrual migraine and in the prevention of climacteric symptoms.

Methods of systematic reviews and meta-analysis preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

Article

Jan 2009
J CLIN EPIDEMIOL

Abstract PR346: The Effect of Epidural Magnesium Injection for Managing Chronic Pain After Thoracotomies

Article

Sep 2016
ANESTH ANALG

Mohammad Yosry

PRISMA harms checklist: improving harms reporting in systematic reviews

Article

Feb 2016
Br Med J

Introduction For any health intervention, accurate knowledge of both benefits and harms is needed. Systematic reviews often compound poor reporting of harms in primary studies by failing to report harms or doing so inadequately. While the PRISMA statement (Preferred Reporting Items for Systematic reviews and Meta-Analyses) helps systematic review authors ensure complete and transparent reporting, it is focused mainly on efficacy. Thus, a PRISMA harms checklist has been developed to improve harms reporting in systematic reviews, promoting a more balanced assessment of benefits and harms. Methods A development strategy, endorsed by the EQUATOR Network and existing reporting guidelines (including the PRISMA statement, PRISMA for abstracts, and PRISMA for protocols), was used. After the development of a draft checklist of items, a modified Delphi process was initiated. The Delphi consisted of three rounds of electronic feedback followed by an in-person meeting. Results The PRISMA harms checklist contains four essential reporting elements to be added to the original PRISMA statement to improve harms reporting in reviews. These are reported in the title (“Specifically mention ‘harms’ or other related terms, or the harm of interest in the review”), synthesis of results (“Specify how zero events were handled, if relevant”), study characteristics (“Define each harm addressed, how it was ascertained (eg, patient report, active search), and over what time period”), and synthesis of results (“Describe any assessment of possible causality”). Additional guidance regarding existing PRISMA items was developed to demonstrate relevance when synthesising information about harms. Conclusion The PRISMA harms checklist identifies a minimal set of items to be reported when reviewing adverse events. This guideline extension is intended to improve harms reporting in systematic reviews, whether harms are a primary or secondary outcome.

Opioid Prescribing for Chronic Pain - Achieving the Right Balance through Education

Article

Jan 2016
NEW ENGL J MED

Daniel P Alford

Groups advocating quick fixes to the opioid-misuse epidemic seek regulations limiting opioid availability, but prescriber education is a more finely tuned approach, allowing us to individualize care appropriately after a careful benefit-risk assessment.

Systematic Review: Treatment Agreements and Urine Drug Testing to Reduce Opioid Misuse in Patients With Chronic Pain

Article

Jun 2010

Joanna L Starrels

Background: Experts recommend opioid treatment agreements and urine drug testing to reduce opioid analgesia misuse, but evidence of their effectiveness has not been systematically reviewed. Purpose: To synthesize studies of the association of treatment agreements and urine drug testing with opioid misuse outcomes in outpatients with chronic noncancer pain. Data sources: MEDLINE, PsycINFO, EMBASE, Cochrane Central Register of Controlled Clinical Trials (January 1966 to June 2009), reference lists, and expert contacts. Study selection: Original research addressing opioid medications, chronic pain, and treatment agreements or urine drug testing, with a sample size of 50 participants or more and published in English, Spanish, or French. Data extraction: Two investigators independently identified eligible studies, extracted data, and assessed study quality. The outcome of opioid misuse was defined as drug abuse, drug misuse, aberrant drug-related behavior, diversion, or addiction. Data synthesis: Of 102 eligible studies, 11 met inclusion criteria; 6 were in pain clinics and 5 were in primary care settings. Four primary care studies examined multicomponent strategies that included interdisciplinary support. All studies were observational and rated as poor to fair quality. In 4 studies with comparison groups, opioid misuse was modestly reduced (7% to 23%) after treatment agreements with or without urine drug testing. In the other 7 studies, the proportion of patients with opioid misuse after treatment agreements, urine drug testing, or both varied widely (3% to 43%). Limitations: Diversity of interventions and opioid misuse measures precluded meta-analysis. Most studies evaluated combinations of interventions. Conclusion: Relatively weak evidence supports the effectiveness of opioid treatment agreements and urine drug testing in reducing opioid misuse by patients with chronic pain. Further research on effective ways to monitor and reduce opioid misuse is needed, especially in primary care settings. Primary funding source: Substance Abuse and Mental Health Services Administration, National Institute on Drug Abuse, and Robert Wood Johnson Foundation.

Combination pharmacotherapy for management of chronic pain: From bench to bedside

Article

Sep 2013

Chronic pain, a frequently neglected problem, is treated with different classes of drugs. Current agents are limited by incomplete efficacy and dose-limiting side-effects. Knowledge of pain processing implicates multiple concurrent mechanisms of nociceptive transmission and modulation. Thus, synergistic interactions of drug combinations might provide superior analgesia and fewer side-effects than monotherapy by targeting of multiple mechanisms. Several trials in neuropathic pain, fibromyalgia, arthritis, and other disorders have assessed various two-drug combinations containing antidepressants, anticonvulsants, non-steroidal anti-inflammatories, opioids, and other agents. In some trials, combined treatment showed superiority over monotherapy, but in others improved benefit or tolerability was not seen. Escalating efforts to develop novel analgesics that surpass the efficacy of current treatments have not yet been successful; therefore, combination therapy remains an important beneficial strategy. Methodological improvements in future translational research efforts are needed to maximise the potential of combination pharmacotherapy for pain.

An Explanatory Study Evaluating the Muscle Relaxant Effects of Intramuscular Magnesium Sulphate for Dystonia in Complex Regional Pain Syndrome

Article

Aug 2013

The treatment of dystonia related to complex regional pain syndrome (CRPS) remains unsatisfactory, raising the need of alternative targets for intervention. In dystonia, pathologic muscle changes may occur, which contributes to stiffness. Because magnesium sulphate may act as a muscle relaxant through its actions on the neuromuscular junction and muscle, we performed an explanatory study of the muscle relaxant effect and safety of intramuscular magnesium sulphate (IMMG) in CRPS patients with dystonia. In a double-blind randomized placebo-controlled crossover study, 30 patients were assigned to 3-week treatments of IMMG and placebo. Treatments were separated by a 1-week washout period. The daily dose of IMMG was 1,000 mg in week 1, 1,500 mg in week 2, and 2,000 mg in week 3. The primary outcome measure was the difference in change in Burke-Fahn-Marsden scores after 3 weeks of treatment between both interventions. Secondary outcomes involved severity of dystonia, myoclonus, tremor, and pain, and functional activity. Data of 22 patients available for the explanatory analysis revealed no significant differences between IMMG and placebo treatment in any of the outcomes. In conclusion, we found no indication of efficacy of IMMG in a daily dose of 2,000 mg as a muscle relaxant in CRPS-related dystonia. In this double-blind placebo-controlled crossover study there was no evidence found of a muscle relaxant effect of intramuscular magnesium sulphate in dystonia related to CRPS. Consequently, there is insufficient support for new studies evaluating the efficacy of other routes of MG administration in CRPS-related dystonia.

Intravenous Magnesium for Chronic Complex Regional Pain Syndrome Type 1 (CRPS-1)

Article

Jul 2013
PAIN MED

To assess the effects of intravenous administration of magnesium on complex regional pain syndrome type 1 (CRPS-1), a randomized double-blind placebo-controlled trial was performed. Fifty-six patients with CRPS-1 (International Association for the Study of Pain Orlando criteria) received MgSO4 70 mg/kg or placebo (NaCl 0.9%) in 4 hours over 5 consecutive days. Pain (BOX-11 and McGill), the level of impairment (Impairment level Sum Score [ISS]), functional limitations (Radboud Skills Questionnaire, Walking Skills Questionnaire/questionnaire rising and sitting down), participation (Impact on Participation and Autonomy [IPA]), and quality of life (Short Form-36, EuroQol, IPA) were evaluated at baseline and at 1, 3, 6, and 12 weeks. No significant differences were found between MgSO4 and placebo on the BOX-11 and ISS at different time points during the trial on intention-to-treat and per-protocol analysis. A significant improvement on the BOX-11 was found after the first week of the trial in both groups (mean 0.7; standard deviation 1.1). For the MgSO4 group, a clinically relevant and statistically significant improvement on the ISS at 1 week (median 5, interquartile range [IQR] -1 to 8) and a significant improvement on the McGill up to 6 weeks (median 2 words, IQR 0-4.5) were found compared with baseline, which were not found in the placebo group. Significant improvement in perceived job participation was found for the MgSO4 group at 12 weeks (median improvement 1.44-1.17; P = 0.01). ISS improved significantly more in patients with a low Hospital Anxiety and Depression Scale (HADS) score (≤10) in the MgSO4 group (mean 4.4 vs mean -3.1; P = 0.02). Administration of the physiological competitive N-methyl-D-aspartate receptor antagonist magnesium in chronic CRPS provides insufficient benefit over placebo. Future research should focus on patients with acute CRPS and early signs and symptoms of central sensitization.

Pharmacotherapy for the prevention of chronic pain after surgery in adults

Article

Jul 2013

Background: Chronic pain can often occur after surgery, substantially impairing patients' health and quality of life. It is caused by complex mechanisms that are not yet well understood. The predictable nature of most surgical procedures has allowed for the conduct of randomized controlled trials of pharmacological interventions aimed at preventing chronic postsurgical pain. Objectives: The primary objective was to evaluate the efficacy of systemic drugs for the prevention of chronic pain after surgery by examining the proportion of patients reporting pain three months or more after surgery. The secondary objective was to evaluate the safety of drugs administered for the prevention of chronic pain after surgery. Search methods: We identified randomized controlled trials (RCTs) of various systemically administered drugs for the prevention of chronic pain after surgery from CENTRAL, MEDLINE, EMBASE and handsearches of other reviews and trial registries. The most recent search was performed on 17 July 2013. Selection criteria: Included studies were double-blind, placebo-controlled, randomized trials involving adults and evaluating one or more drugs administered systemically before, during or after surgery, or both, which measured pain three months or more after surgery. Data collection and analysis: Data collected from each study included the study drug name, dose, route, timing and duration of dosing; surgical procedure; proportion of patients reporting any pain three months or more after surgery, reporting at least 4/10 or moderate to severe pain three months or more after surgery; and proportion of participants dropping out of the study due to treatment-emergent adverse effects. Main results: We identified 40 RCTs of various pharmacological interventions including intravenous ketamine (14 RCTs), oral gabapentin (10 RCTs), oral pregabalin (5 RCTs), non-steroidal anti-inflammatories (3 RCTs), intravenous steroids (3 RCTs), oral N-methyl-D-aspartate (NMDA) blockers (3 RCTs), oral mexiletine (2 RCTs), intravenous fentanyl (1 RCT), intravenous lidocaine (1 RCT), oral venlafaxine (1 RCT) and inhaled nitrous oxide (1 RCT). Meta-analysis suggested a modest but statistically significant reduction in the incidence of chronic pain after surgery following treatment with ketamine but not gabapentin or pregabalin. Results with ketamine should be viewed with caution since most of the included trials were small (that is < 100 participants per treatment arm), which could lead to the overestimation of treatment effect. Authors' conclusions: Additional evidence from better, well designed, large-scale trials is needed in order to more rigorously evaluate pharmacological interventions for the prevention of chronic pain after surgery. Furthermore, available evidence does not support the efficacy of gabapentin, pregabalin, non-steroidal anti-inflammatories, intravenous steroids, oral NMDA blockers, oral mexiletine, intravenous fentanyl, intravenous lidocaine, oral venlafaxine or inhaled nitrous oxide for the prevention of chronic postoperative pain.

The Costs and Consequences of Adequately Managed Chronic Non‐Cancer Pain and Chronic Neuropathic Pain

Article

Mar 2013
Pain Pract

Background Chronic pain is distressing for patients and a burden on healthcare systems and society. Recent research demonstrates different aspects of the negative impact of chronic pain and the positive impact of successful treatment, making an overview of the costs and consequences of chronic pain appropriate. Objective To examine recent literature on chronic noncancer and neuropathic pain prevalence, impact on quality and quantity of life, societal and healthcare costs, and impact of successful therapy. Methods Systematic reviews (1999 to February 2012) following PRISMA guidelines were conducted to identify studies reporting appropriate outcomes. ResultsChronic pain has a weighted average prevalence in adults of 20%; 7% have neuropathic pain, and 7% have severe pain. Chronic pain impeded activities of daily living, work and work efficiency, and reduced quality and quantity of life. Effective pain therapy (pain intensity reduction of at least 50%) resulted in consistent improvements in fatigue, sleep, depression, quality of life, and work. Conclusion Strenuous efforts should be put into obtaining good levels of pain relief for people in chronic pain, including the opportunity for multiple drug switching, using reliable, validated, and relatively easily applied patient-centered outcomes. Detailed, thoughtful and informed decision analytic policy modeling would help understand the key elements in organizational change or service reengineering to plan the optimum pain management strategy to maximize pain relief and its stream of benefits against budgetary and other constraints. This paper contains the information on which such models can be based.

Effect of Epidural Magnesium on the Incidence of Chronic Postoperative Pain After Video-Assisted Thoracic Surgery

Article

Aug 2012

Objective: The aim of this study was to determine whether the epidural administration of magnesium during the perioperative period decreased the incidence of chronic postoperative pain (CPOP) at 3 months after video-assisted thoracic surgery. Design: Prospective, randomized, and blinded. Setting: A university hospital. Participants: Patients. Interventions: Before the induction of anesthesia, the patients were assigned randomly to receive normal saline, 5 mL, (group C, n = 72) or magnesium sulfate, 100 mg (group M, n = 72), epidurally. At the end of surgery, group C received a continuous infusion of a mixture of 0.2% ropivacaine, 226 mL, and fentanyl, 1,200 μg, through a patient-controlled epidural analgesia pump for 48 hours. In group M, magnesium sulfate, 500 mg, was added to the infusion. Measurements and main results: The incidence and severity of CPOP were assessed by a telephone survey 3 months after surgery. Patients were asked whether they experienced pain and to rank the severity of the pain using a 3-point scale (1, mild; 2, moderate; 3, severe). The incidences of CPOP were 42.4% in group C and 49.1% in group M. The severities of pain in the patients with CPOP were 1.0 (1-2) in group C and 1.0 (1-2) in group M. The incidence and severity of CPOP did not differ between the 2 groups. Conclusions: The epidural administration of magnesium from before the induction of anesthesia to 48 hours postoperatively did not decrease significantly the incidence or severity of CPOP in patients undergoing video-assisted thoracic surgery.

Variation in the placebo effect in randomised controlled trials of analgesics: All is as blind as it seems

Article

Mar 1996

The objective was to investigate the relationship between pain relief scores produced by placebo and by active interventions in randomised controlled trials (RCTs). Individual patient categorical pain relief scores from 5 placebo-controlled single-dose parallel-group RCTs in acute postoperative pain were used to calculate the percentage of the maximum possible pain relief score (%maxTOTPAR) for the different treatments. One hundred and thirty of the 525 patients in the 5 trials had a placebo. Individual patients' scores with placebo varied from 0 to 100% of the maximum possible pain relief. The proportion who obtained more than 50% of the maximum possible pain relief with placebo varied from 7% to 37% across the trials; with the active drugs the variation was from 5 to 63%. Mean placebo scores were related to the mean score for the active treatments in each study; the higher the mean active score, the higher the mean placebo score. This relationship disappeared when median values were used. Medical folklore has it that the amount of relief obtained with placebo is one-third of the maximum possible (and does not vary), and that one-third of patients respond to placebo. The results show that the amount of relief obtained with placebo varies considerably between patients, that 38% of patients obtained more than 10% of the maximum possible relief, and 16% obtained greater than 50%. In double-blind, randomised parallel-group studies of high quality placebo scores should not vary. Despite these conditions being met the placebo scores did vary. The previous explanation, of a relationship between the mean placebo scores and the mean scores for the active treatments was not supported.

Magnesium and MK-801 have a similar effect in two experimental models of neuropathic pain

Article

Jan 2001
BRAIN RES

Considering that magnesium and non-competitive NMDA receptor antagonists inhibit the opening of the channel linked to the NMDA receptor, we assessed their effects on mechanical hyperalgesia in two animal models of neuropathic pain (rats with a sciatic nerve ligature and diabetic rats). Our data show that magnesium reverses the hyperalgesia, as does MK-801. These results suggest that magnesium could be an alternative for the treatment of neuropathic pain in patients.

Magnesium involvement in pain

Article

Nov 2011
MAGNESIUM RES

Mihai Nechifor

mrh.2011.0296 Auteur(s) : Mihai Nechifor mnechif@yahoo.com Department of pharmacology, Gr. T. Popa University of Medicine and Pharmacy, Iasi, Romania Correspondence. Mihai Nechifor, Department of Pharmacology, Gr. T. Popa University of Medicine and Pharmacy, Universitatii 16, Iasi 700115 Romania, Tel. 0040-232-220875, 0040-744-50-8642. The very interesting paper of Pickering et al. [1] raises the issue of the involvement of this cation in different types of pain. Pain is very [...]

Fixed-dose combination of enteric-coated naproxen and immediate-release esomeprazole has comparable efficacy to celecoxib for knee osteoarthritis: Two randomized trials

Article

Jun 2011
CURR MED RES OPIN

To demonstrate that a fixed-dose combination of enteric-coated naproxen 500 mg and immediate-release esomeprazole magnesium 20 mg has comparable efficacy to celecoxib for knee osteoarthritis. Two randomized, double-blind, parallel-group, placebo-controlled, multicenter phase III studies (PN400-307 and PN400-309) enrolled patients aged ≥50 years with symptomatic knee osteoarthritis. Following an osteoarthritis flare, patients received naproxen/esomeprazole magnesium twice daily, celecoxib 200 mg once daily, or placebo for 12 weeks. NCT00664560 and NCT00665431. Three co-primary efficacy endpoints were mean change from baseline to week 12 in Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain and function subscales, and Patient Global Assessment of osteoarthritis using a visual analog scale (PGA-VAS). In Study 307, 619 patients were randomized and 614 treated. In Study 309, 615 patients were randomized and 610 treated. Both naproxen/esomeprazole magnesium and celecoxib were associated with improvements (least squares mean change from baseline to week 12) in WOMAC pain (Study 307: -42.0 and -41.8, respectively; Study 309: -44.2 and -42.9, respectively), WOMAC function (Study 307: -36.4 and -36.3, respectively; Study 309: -38.9 and -36.8, respectively), and PGA-VAS (Study 307: 21.2 and 21.6, respectively; Study 309: 29.0 and 25.6, respectively). A prespecified non-inferiority margin of 10 mm between naproxen/esomeprazole magnesium and celecoxib was satisfied for each co-primary endpoint at week 12 in both studies. Significant improvements were observed with naproxen/esomeprazole magnesium versus placebo in both studies (p < 0.05). Celecoxib was significantly different from placebo in Study 307 (p < 0.05); however, the improvements were not significant in Study 309. Acetaminophen use and patient expectation of receiving active treatment (80% probability) may have contributed to a high placebo response observed. Naproxen/esomeprazole magnesium has comparable efficacy to celecoxib for the management of pain associated with osteoarthritis of the knee over 12 weeks.

Improving neuropathy scores in type 2 diabetic patients using micronutrients supplementation

Article

Apr 2011

Magnesium-Essentials for Anesthesiologists

Article

Feb 2011
ANESTHESIOLOGY

Magnesium plays a fundamental role in many cellular functions, and thus there is increasing interest in its role in clinical medicine. Although numerous experimental studies indicate positive effects of magnesium in a variety of disease states, large clinical trials often give conflicting results. However, there is clear evidence for magnesium to benefit patients with eclampsia or torsades de pointes arrhythmias. In addition, magnesium seems to have antinociceptive and anesthetic as well as neuroprotective effects, yet well-designed large clinical trials are required to determine its actual efficacy in pain management or in the state of stroke or subarachnoid hemorrhage. The current review aims to provide an overview of current knowledge and available evidence with respect to physiologic aspects of magnesium and proposed indications and recommendations for its use in the clinical setting.

NMDA Receptor Antagonists for the Treatment of Neuropathic Pain

Article

Nov 2010
PAIN MED

The N-methyl-D-Aspartate (NMDA) receptor has been proposed as a primary target for the treatment of neuropathic pain. The aim of the present study was to perform a meta-analysis evaluating the effects of (individual) NMDA receptor antagonists on neuropathic pain, and the response (sensitivity) of individual neuropathic pain disorders to NMDA receptor antagonist therapy. PubMed (including MEDLINE), EMBASE and CENTRAL were searched up to October 26, 2009 for randomized placebo controlled trials (RCTs) on neuropathic pain. The methodological quality of the included trials was independently assessed by two authors using the Delphi list. Fixed or random effects model were used to calculate the summary effect size using Hedges' g. NA. The patients used for the study were neuropathic pain patients. The interventions used were NMDA receptor antagonists. The outcome of measurements was the reduction of spontaneous pain. Twenty-eight studies were included, meeting the inclusion criteria. Summary effect sizes were calculated for subgroups of studies evaluating ketamine IV in complex regional pain syndrome (CRPS), oral memantine in postherptic neuralgia and, respectively, ketamine IV, and oral memantine in postamputation pain. Treatment with ketamine significantly reduced pain in postamputation pain (pooled summary effect size: -1.18 [confidence interval (CI) 95% -1.98, -0.37], P = 0.004). No significant effect on pain reduction could be established for ketamine IV in CRPS (-0.65 [CI 95% -1.47, 0.16], P = 0.11) oral memantine in postherptic neuralgia (0.03 [CI 95% -0.51, 0.56], P = 0.92) and for oral memantine in postamputation pain (0.38 [CI 95% -0.21, 0.98], P = 0.21). Based on this systematic review, no conclusions can yet be made about the efficacy of NMDA receptor antagonists on neuropathic pain. Additional RCTs in homogenous groups of pain patients are needed to explore the therapeutic potential of NMDA receptor antagonists in neuropathic pain.

Intravenous Magnesium for Complex Regional Pain Syndrome Type 1 (CRPS 1) Patients: A Pilot Study

Article

Jul 2009
PAIN MED

To explore the feasibility of intravenous magnesium administration as a potential candidate intervention for a large size trial in Complex Regional Pain Syndrome Type 1 (CRPS 1). Randomized clinical trial. Outpatient pain clinic. Ten CRPS 1 patients. Eight patients received 70 mg/kg magnesium sulphate infusions in 4 hours for 5 days. For blinding purposes, 2 patients received equal amount NaCl 0.9% solutions (data not analyzed or presented). Interventions were accompanied by standardized physical therapy. Pain was assessed using an 11-point Box scale (three times daily for a week) and the McGill Pain Questionnaire. Skin sensitivity was measured with the Semmes Weinstein Monofilaments, (other) impairments with the Impairment Level Sumscore. In addition, functional limitations (Radboud Skills Questionnaire, questionnaire rising and sitting down) and quality of life (Short Form-36 [SF-36], EuroQol) were evaluated. Assessments were performed at baseline, 1, 3, 6, and 12 weeks after intervention. Mild systemic side effects were experienced and the infusions were locally well tolerated. Pain was significantly reduced at all follow up compared with baseline (T1: P = 0.01, T3: P = 0.04, T6: P = 0.02, T12: P = 0.02). McGill sensory subscale improved significantly at T1 (number of words chosen: P = 0.03 and pain rating index: P = 0.03). Impairment level (P = 0.03) and quality of life (EuroQol P = 0.04, SF-36 physical P = 0.01) were significantly improved at T12. No improvement was found for skin sensitivity and functional limitations. Intravenous magnesium significantly improved pain, impairment and quality of life and was well tolerated. The results of this pilot study are encouraging and suggest that magnesium IV as a treatment in CRPS 1 should be further explored in a large size formal trial design.

Role of spinal NMDA receptors, protein kinase C and nitric oxide synthase in the hyperalgesia induced by magnesium deficiency in rats

Article

Dec 2001

Magnesium (Mg)-deficient rats develop a mechanical hyperalgesia which is reversed by a N-Methyl-D-Aspartate (NMDA) receptor antagonist. Given that functioning of this receptor-channel is modulated by Mg, we wondered whether facilitated activation of NMDA receptors in Mg deficiency state may in turn trigger a cascade of specific intracellular events present in persistent pain. Hence, we tested several antagonists of NMDA and non-NMDA receptors as well as compounds interfering with the functioning of intracellular second messengers for effects on hyperalgesia in Mg-deficient rats. Hyperalgesic Mg-deficient rats were administered intrathecally (10 μl) or intraperitoneally with different antagonists. After drug injection, pain sensitivity was evaluated by assessing the vocalization threshold in response to a mechanical stimulus (paw pressure test) over 2 h. Intrathecal administration of MgSO4 (1.6, 3.2, 4.8, 6.6 μmol) as well as NMDA receptor antagonists such as MK-801 (0.6, 6.0, 60 nmol), AP-5 (10.2, 40.6, 162.3 nmol) and DCKA (0.97, 9.7, 97 nmol) dose-dependently reversed the hyperalgesia. Chelerythrine chloride, a protein kinase C (PKC) inhibitor (1, 10.4, 104.2 nmol) and 7-NI, a specific nitric oxide (NO) synthase inhibitor (37.5, 75, 150 μmol kg−1, i.p.) induced an anti-hyperalgesic effect in a dose-dependent manner. SR-140333 (0.15, 1.5, 15 nmol) and SR-48968 (0.17, 1.7, 17 nmol), antagonists of neurokinin receptors, produced a significant, but moderate, increase in vocalization threshold. These results demonstrate that Mg-deficiency induces a sensitization of nociceptive pathways in the spinal cord which involves NMDA and non-NMDA receptors. Furthermore, the data is consistent with an active role of PKC, NO and, to a lesser extent substance P in the intracellular mechanisms leading to hyperalgesia. British Journal of Pharmacology (2001) 134, 1227–1236; doi:10.1038/sj.bjp.0704354

Excitotoxic Amino Acids and Neuropsychiatric Disorders

Article

Feb 1990

John W. Olney

Magnesium bioavailability from magnesium citrate and magnesium oxide

Article

Mar 1990

This study compared magnesium oxide and magnesium citrate with respect to in vitro solubility and in vivo gastrointestinal absorbability. The solubility of 25 mmol magnesium citrate and magnesium oxide was examined in vitro in solutions containing varying amounts of hydrochloric acid (0-24.2 mEq) in 300 ml distilled water intended to mimic achlorhydric to peak acid secretory states. Magnesium oxide was virtually insoluble in water and only 43% soluble in simulated peak acid secretion (24.2 mEq hydrochloric acid/300 ml). Magnesium citrate had high solubility even in water (55%) and was substantially more soluble than magnesium oxide in all states of acid secretion. Reprecipitation of magnesium citrate and magnesium oxide did not occur when the filtrates from the solubility studies were titrated to pH 6 and 7 to stimulate pancreatic bicarbonate secretion. Approximately 65% of magnesium citrate was complexed as soluble magnesium citrate, whereas magnesium complexation was not present in the magnesium oxide system. Magnesium absorption from the two magnesium salts was measured in vivo in normal volunteers by assessing the rise in urinary magnesium following oral magnesium load. The increment in urinary magnesium following magnesium citrate load (25 mmol) was significantly higher than that obtained from magnesium oxide load (during 4 hours post-load, 0.22 vs 0.006 mg/mg creatinine, p less than 0.05; during second 2 hours post-load, 0.035 vs 0.008 mg/mg creatinine, p less than 0.05). Thus, magnesium citrate was more soluble and bioavailable than magnesium oxide.

Magnesium in migraine. Results of a multicenter pilot study

Article

Sep 1994
Fortschr Med

K Taubert

Numerous experiments and clinical observations have credited magnesium with a positive influence on the incidence of migraine attacks. With the aim of testing this hypothesis, a doubleblind, cross-over multicenter pilot study was initiated. The study contained 43 migraine patients who met the criteria of the international Headache Society. Administration of 600 mg magnesium/day in the form of trimagnesium dieitrate for prophylaxis. Under this medication, a significant reduction in the incidence of migraine attacks was observed. Although the level of effectiveness of the regimen does not appear to be as high as that of presently approved migraine prophylactic substances, a very low rate of side effects can be expected. The working hypothesis to the effect that magnesium may be useful in the prevention of migraine attacks has been confirmed by the pilot study. Further studies aimed at determining dosage and enabling a further differentiation of patient material are in preparation.

Treatment of fibromyalgia syndrome with Super Malic®: A randomized, double blind, placebo controlled, crossover pilot study

Article

Jun 1995

To study the efficacy and safety of Super Malic, a proprietary tablet containing malic acid (200 mg) and magnesium (50 mg), in treatment of primary fibromyalgia syndrome (FM). Twenty-four sequential patients with primary FM were randomized to a fixed dose (3 tablets bid), placebo controlled, 4-week/course, pilot trial followed by a 6-month, open label, dose escalation (up to 6 tablets bid) trial. A 2-week, medication free, washout period was required before receiving treatment, between blinded courses, and again before starting open label treatment. The 3 primary outcome variables were measures of pain and tenderness but functional and psychological measures were also assessed. No clear treatment effect attributable to Super Malic was seen in the blinded, fixed low dose trial. With dose escalation and a longer duration of treatment in the open label trial, significant reductions in the severity of all 3 primary pain/tenderness measures were obtained without limiting risks. These data suggest that Super Malic is safe and may be beneficial in the treatment of patients with FM. Future placebo-controlled studies should utilize up to 6 tablets of Super Malic bid and continue therapy for at least 2 months.

Prophylaxis of Migraine with Oral Magnesium: Results From A Prospective, Multi-Center, Placebo-Controlled and Double-Blind Randomized Study

Article

Jul 1996

In order to evaluate the prophylactic effect of oral magnesium, 81 patients aged 18-65 years with migraine according to the International Headache Society (IHS) criteria (mean attack frequency 3.6 per month) were examined. After a prospective baseline period of 4 weeks they received oral 600 mg (24 mmol) magnesium (trimagnesium dicitrate) daily for 12 weeks or placebo. In weeks 9-12 the attack frequency was reduced by 41.6% in the magnesium group and by 15.8% in the placebo group compared to the baseline (p < 0.05). The number of days with migraine and the drug consumption for symptomatic treatment per patient also decreased significantly in the magnesium group. Duration and intensity of the attacks and the drug consumption per attack also tended to decrease compared to placebo but failed to be significant. Adverse events were diarrhea (18.6%) and gastric irritation (4.7%). High-dose oral magnesium appears to be effective in migraine prophylaxis.

Magnesium in the Prophylaxis of Migraine—A Double-Blind, Placebo-Controlled Study

Article

Nov 1996

The migraine prophylactic effect of 10 mmol magnesium twice-daily has been evaluated in a multicentre, prospective, randomized, double-blind, placebo-controlled study. Patients with two to six migraine attacks per month without aura, and history of migraine of at least 2 years, were included. A 4-week baseline period without medication was followed by 12 weeks of treatment with magnesium or placebo. The primary efficacy end-point was a reduction of at least 50% in intensity or duration of migraine attacks in hours at the end of the 12 weeks of treatment compared to baseline. With a calculated total sample size of 150 patients, an interim analysis was planned after completing treatment of at least 60 patients, which in fact was performed with 69 patients (64F, 5M), aged 18-64 years. Of these, 35 had received magnesium and 34 placebo. The number of responders was 10 in each group (28.6% under magnesium and 29.4% under placebo). As determined in the study protocol, this was a major reason to discontinue the trial. With regard to the number of migraine days or migraine attacks there was no benefit with magnesium compared to placebo. There were no centre-specific differences, and the final assessments of treatment efficacy by the doctor and patient were largely equivocal. With respect to tolerability and safety, 45.7% of patients in the magnesium group reported primarily mild adverse events like soft stool and diarrhoea in contrast to 23.5% in the placebo group.

The Use of NMDA-Receptor Antagonists in the Treatment of Chronic Pain

Article

Jul 2000

David James Hewitt

Chronic pain can be maintained by a state of sensitization within the central nervous system that is mediated in part by the excitatory amino acids glutamate and aspartate binding to the N-methyl-D-aspartate (NMDA) receptor. A number of antagonists to the NMDA receptor are antinociceptive in animal models but are associated with significant dose-limiting side effects. Commercially available NMDA-receptor antagonists include ketamine, dextromethorphan, memantine, and amantadine. The opioids methadone, dextropropoxyphene, and ketobemidone are also antagonists at the NMDA receptor. The NMDA-receptor antagonists have a significant impact on the development of tolerance to opioid analgesics. Consequently, NMDA-receptor antagonists may represent a new class of analgesics and may have potential as coanalgesics when used in combination with opioids.

Efficacy and Safety of Magnesium for the Management of Chronic Pain in Adults: A Systematic Review

Abstract

No full-text available

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