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Nutritional Modulators of Pain in the Aging Population
Abstract
It is believed that 40–60% of Americans use complementary and alternative medicine to treat a variety of medical conditions. Of these Americans, 30% cite pain as the primary condition being treated. The clinical use of nutritional modulators as a treatment of pain has been widely studied. Pain states such as myalgias from statin use, rheumatoid arthritis, menstrual pain, and osteoarthritis, just to name a few, have been investigated. Strong evidence supports the use of probiotics, omega-3 fatty acids, magnesium, glucosamine/chondroitin, and vitamin D in a variety of pain states. Other modulators including turmeric, devil’s claw, methylsulfonylmethane (MSM), Boswellia, white willow bark, and green tea have contradictory or minimal evidence to support their use for pain relief. Despite the medical evidence or lack thereof, passionate consumers continue to utilize these modulators as supplements or alternatives to traditional pharmacotherapy.
... studies have found that aqueous extracts derived from poplar buds do not cause irritation when tested on the SIRC cell line, and this suggests that these extracts could be suitable for use in the development of eye drop formulations [9]. These buds extracts are also suitable for treating rheumatoid arthritis, as salicin, gallic acid, and salicortin found in poplar buds help to reduce joint pain and swelling [10,13,14]. Moreover, poplar buds possess antiseptic, diuretic, and anti-inflammatory properties [14,15]. ...
... Currently, there is increasing interest among researchers in the plant species of the Salicaceae family, known for their capacity to accumulate phenolic acids, flavonoids, and salicin derivatives [4,5]. Phenolic compounds encountered in the buds of poplar trees have been established to possess a spectrum of bioactive properties, including anti-inflammatory, antioxidant, antimicrobial, and wound-healing attributes [6][7][8][9][10]. These properties render them valuable assets in the therapeutic management of various disorders [11,12]. ...
Balsam poplar buds have been used for wound healing and treating irritated skin in traditional medicine. Balsam poplar buds extracts exhibit anti-inflammatory, antioxidant, and antimicrobial effects. In recent years, scientific research has begun to validate some of these traditional uses, leading to an increased interest in balsam poplar buds as a potential source of natural remedies in modern medicine. The study aims to simulate semi-solid pharmaceutical forms with balsam poplar buds extract and evaluate their quality through biopharmaceutical research. The active compounds identified in Lithuanian poplar buds were p-coumaric acid, cinnamic acid, caffeic acid, galangin, pinocembrin, pinobanksin, and salicin. In gels, pH values ranged from 5.85 ± 0.05 to 5.95 ± 0.07. The determined pH values of emulgels ranged from 5.13 ± 0.05 to 5.66 ± 0.15. After 6 h, the release of active compounds from gels and emulgels ranged from 47.40 ± 2.41% to 71.17 ± 3.54. p-coumaric acid dominates in the balsam poplar buds extracts. The pH values of the prepared sem-solid pharmaceutical forms are suitable for use on the skin. The viscosity of the formulations depends on the amount of gelling agent. All formulations showed antioxidant activity. It is relevant to conduct a more extensive study on the influence of the chosen carrier on the release of active compounds from semi-solid formulations with an extract of balsam poplar buds.
... The presence of salicin made the herbal product act as a pain reliever. Similar to aspirin, it also inhibits COX 1 and 2 and therefore blocks PGs and acts as an anti-inflammatory agent [71][72]. But unlike aspirin which is known to cause gastric problems, the presence of a gastroprotective agent reduces the damage of gastrointestinal mucosa [73]. ...
... The salicin component in herbal products has been effective in relieving pain. Similar to aspirin, it also inhibits COX-1 and COX-2 and therefore acts as an anti-inflammatory agent by blocking PGs [71][72]. But unlike aspirin which is known to cause gastric problems, it reduces the damage of gastrointestinal mucosa [73]. ...
Background
The cyclooxygenase (COX) and lipoxygenase (LOX) enzymes catalyze the production of pain mediators like prostaglandins (PGs) and leukotrienes (LTs) respectively from arachidonic acid.
Introduction
The COX and LOX enzyme modulators are responsible for the major PGs and LTs mediated complications like asthma, osteoarthritis, rheumatoid arthritis, cancer, Alzheimer’s disease, neuropathy and cardiovascular syndromes (CVS). Many synthetic nonsteroidal anti-inflammatory drugs (NSAIDs) used in the treatment have serious side effects like nausea, vomiting, hyperacidity, gastrointestinal ulcers, CVS, etc.
Methods
The natural inhibitors of pain mediators have great acceptance worldwide due to fewer side effects on long-term uses. The present review is an extensive study of the advantages of plant-based vs synthetic inhibitors.
Results
These natural COX and LOX inhibitors control inflammatory response without causing side-effect-related complicacy.
Conclusion
Therefore, the natural COX and LOX inhibitors may be used as alternative medicines for the management of pain and inflammation due to their less toxicity and resistivity.
... Chi et al. [23] also supported that providing sufficient training in pain management can improve family caregiver outcomes. In the present study, there was a decrease in the caregivers' physical and emotional burden when the pain severity and physical health of the participants had improved, resulting in a reduced workload for the caregivers in taking care of the older adults' chronic pain and daily activities [24]. ...
The COVID-19 pandemic started at the beginning of 2020. It significantly impacted the older adults in Hong Kong, with most of the community centers and elderly centers being closed down under various restrictive measures. Thus, community-based health promotion activities were temporarily paused, which decreased older adults’ health-promoting behaviors and motivation to stay active. This research aimed to improve the quality of life and the health of older adults with chronic pain through the pain management program. This study was conducted face-to-face on the campus of Hong Kong Metropolitan University. This dyadic pain management program (DPM) was an 8-week group-based program. The DPM comprised 4 weeks of campus-based activities and 4 weeks of digital-based activities delivered via a WhatsApp group. An 80% participation rate in the campus-based activities was regarded as completing the DPM. The control group only received lesson leaflets. Pain intensity, pain self-efficacy, psychological health of pain victims, caregiver burden inventory, and a semi-structured interview were evaluated at week 1 (T0), week 8 (T1), and week 12 (T2) after randomization. The IBM-SPSS version 22 was used to perform statistical analyses. Using non-pharmacological methods and regular exercise for 12 weeks improved physical health in terms of pain intensity, pain self-efficacy, and psychological health in anxiety, depression, and stress. For caregivers, their burden decreased after the pain management program. These findings indicated that Pender’s Health Promotion Model is helpful to empower the participants and their caregivers with knowledge, skills, and power to manage their chronic pain situations. Utilizing this model as a framework, Researchers can design more effective non-pharmacological interventions for older adults to increase their engagement in health-promoting activities in the community.
... are attributed to bioactive compounds such as phenolic glycoside (e.g., salicin), flavonoids (e.g., luteolin, kaempferol, and epicatechin gallate), and other phenolic compounds (e.g., catechin, syringic acid, and salicylic acid) [4][5][6]. In the case of salicin, it is absorbed after ingestion and metabolized into saligenin (in the intestine), and then into salicylic acid (in the liver), finally blocking inflammatory prostaglandins by inhibiting cyclooxygenase 1 and 2 [7,8]. Luteolin, one of the flavones, is widely contained in medicinal plants and has immunopharmacological activities [9]. ...
For a long time, species of the genus Salix have been widely utilized and studied as medicinal plants; however, the biological activity and phytochemical composition of Salix schwerinii (SS) and S. kochiana (SK) have not been studied at all. This study investigated the antioxidant properties of SS and SK extracts and detected phytochemical compounds in the extracts. The results showed that the antioxidant activities (IC50) of SS extract, SK extract, and ascorbic acid (reference) were as follows, respectively: 169.8, 79.8, and 71.2 μg mL−1 for ABTS cation radical scavenging and 38.4, 26.2, and 9.3 μg mL−1 for DPPH free radical scavenging. The results imply that SK has a high potential as a natural antioxidant. The phytochemical compositions of extracts (mg g−1) were analyzed as follows: SS extracts, 217.7 phenolics (1.54 catechin, 0.86 syringic acid, 0.46 luteolin, and others) and 5.06 salicin; SK extracts, 71.0 phenolics (0.54 catechin, 0.28 myricetin, 0.12 salicylic acid, and others) and 2.11 salicin. Compared to previous studies, the present findings go further to highlight that SS deserves attention as a novel source of salicin. The present study highlights the need for further studies on the aspects of medicinal functions of the extracts, bioprocess design for efficient phytochemical extraction, and applications of bioactive substances.
... It is a precursor to acetylsalicylic acid and has documented anti-inflammatory properties [12], including an inhibitory effect on TNF-a [13]. Whereas TNF-a inhibitors are typically administered via injection, salicin is ingested [14] and has no noted serious side effects [15,16], fewer even than its synthetic counterpart, aspirin, and other non-steroidal anti-inflammatory drugs (NSAIDs), all of which can damage the gastrointestinal mucosa [17]. ...
Cellular senescence is strongly tied to vascular disease. The current study aims to examine ways that endothelial cellular senescence can be prevented and the mechanisms by which prevention of senescence occurs. Human umbilical vein endothelial cells were exposed to TNF-α to induce senescence; then salicin was administered in two doses – 50 and 100 µM – to establish a dose-dependent effect of salicin on SA-β-Gal, G1 cell cycle arrest, expression of p21 and PAI-1, p53 acetylation at K382, NRF2 and oxidative stress. NRF2 was examined as a mediating mechanism of salicin’s impact on cellular senescence and was found to account for salicin’s impact on SA-β-Gal, p21, PAI-1 and p53. Together, these results provide a compelling case that salicin has a substantial impact on numerous factors tied to cellular senescence in human endothelial cells. Thus, treatment with salicin may hold promise as a means of preventing aging-related vascular disease. Furthermore, salicin appears to operate via a functional pathway that is different from that affected by anti-inflammatory drugs (e.g. aspirin).
Since ancient natural resins played an important role in the daily life and rituals of religious ceremonies due their aromatic odor various medicinal effects. Boswellia, one of the most important natural resins, is the subject of our research. The Boswellia plants belong to species of Bruceracera family. They produce fragrant resins given by laticiferous ducts through a process of incising the bark of the branches; a yellow gum is released, then becomes hard upon exposure to natural conditions in small granules known as Boswellia resins or frankincense.
Through the study of combinations and mixtures mentioned in some manuscripts and modern research, it was found that frankincense was used in several fields in different historical periods. It is still used in religious ceremonies in Roman Catholic, Episcopal, Orthodox and Indian churches.
Since ancient medicine, frankincense was used as antiseptic, anti-inflammatory and anti-bleeding. Over the last twenty years, scientists and pharmaceutical companies have been working to reveal the best types of frankincense, and its indications to highlight its various medical effects and identify the active constituents.
Therefore, the goal of this research is to compare the most important uses of frankincense in pharmaceutical products mentioned through the ancient civilizations with its modern uses. Its indications, impact mechanism and side effects, if exist, are determined
Diabetic neuropathy encompasses multiple pathological disturbances, many of which coincide with the pathophysiological mechanisms of neurodegenerative disorders. In the present study, various biophysical techniques like Rayleigh light scattering assay, Thioflavin T assay, far-UV Circular Dichroism spectroscopy, Transmission electron microscopy have unveiled the anti-fibrillatory effect of esculin upon human insulin fibrillation. MTT cytotoxicity assay demonstrated the biocompatibility of esculin and in-vivo studies such as behavioral tests like hot plate test, tail immersion test, acetone drop test, plantar test were performed for validating diabetic neuropathy. Assessment of levels of serum biochemical parameters, oxidative stress parameters, pro-inflammatory cytokines as well as neuron specific markers was done in the current study. Rat brains were subjected to histopathology and their sciatic nerves were subjected to transmission electron microscopy to analyze myelin structure alterations. All these results reveal that esculin ameliorates diabetic neuropathy in experimental diabetic rats. Conclusively, our study demonstrates the anti-amyloidogenic potential of esculin in the form of inhibition of human insulin fibrillation, making it a promising candidate in combating neurodegenerative disorders in the near future and the results of various behavioral, biochemical, and molecular studies reveal that esculin possesses anti-lipidemic, anti-inflammatory, anti-oxidative and neuroprotective properties which help in ameliorating diabetic neuropathy in streptozotocin induced diabetic Wistar rats.
The natural process of aging gradually causes changes in living organisms, leading to the deterioration of organs, tissues, and cells. In the case of osteoarthritis (OA), the degradation of cartilage is a result of both mechanical stress and biochemical factors. Natural products have already been evaluated for their potential role in the prevention and treatment of OA, providing a safe and effective adjunctive therapeutic approach. This review aimed to assess the therapeutic potential of natural products and their derivatives in osteoarthritis via a systematic search of literature after 2008, including in vitro, in vivo, ex vivo, and animal models, along with clinical trials and meta-analysis. Overall, 170 papers were obtained and screened. Here, we presented findings referring to the preventative and therapeutic potential of 17 natural products and 14 naturally occurring compounds, underlining, when available, the mechanisms implicated. The nature of OA calls to initially focus on the management of symptoms, and, in that context, several naturally occurring compounds have been utilized. Underlying a global need for more sustainable natural sources for treatment, the evidence supporting their chondroprotective potential is still building up. However, arriving at that kind of solution requires more clinical research, targeting the implications of long-term treatment, adverse effects, and epigenetic implications.
A vast majority of the world’s population lacks access to essential medicines
and the provision of safe healthcare services. Medicinal plants and herbal
medicines can be applied for pharmacognosy, or the discovery of new drugs, or as an aid for plant physiology studies. In recent years, there has been increased interest in the search for new chemical entities and the expression of resistance of many drugs available in the market has led to a shift in paradigm towards medicinal research. Herbal treatments, the most popular form of folk medicine, may become an important way of increasing access to healthcare services.
Advanced Pharmacological Uses of Medicinal Plants and Natural Products provides emerging research exploring the theoretical and practical aspects of drug discovery from natural sources that allow for the effective treatment of human health problems without any side effects, toxicity, or drug resistance.
Featuring coverage on a broad range of topics such as ethnobotany, therapeutic applications, and bioactive compounds, this book is ideally designed for pharmacologists, scientists, ethnobotanists, botanists, health researchers, professors, industry professionals, and health students in fields that include pharmaceutical drug development and discovery.
Traditionally, the gum resin produced from the Boswellia serrata plant has been used in as a therapeutical compound. The gum that contains a chemical known as boswellic acid, AKBA (3-O-acetyl-11 keto-β-boswellic acid), and widely in ayurvedic medicines. This is used to treat the disease like reduction in various inflammatory conditions of the skin, eye, as well as respiratory disorders such as asthma, bronchitis, and laryngitis. The boswellic acids were also found capable to inhibit both hemolysis and chemotaxis of leukocytes and were shown to work by inhibiting C3-convertase, a key enzyme of the classical complementary pathway. In addition to this, the compound shows beneficial effects in various pharmacological properties like immunomodulation activity, polyarthritis, activity against Hepatitis C-virus and other harmful microbes, Colitis and Crohn's disease, and so on. The boswellic acid is also used to treat patients with memory disorders. In this chapter, the chemical nature and isolation of boswellic acid and its therapeutic importance have been highlighted.
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.
In a previous three-month study of Meriva, a proprietary curcumin-phosphatidylcholine phytosome complex, decreased joint pain and improvement in joint function were observed in 50 osteoarthritis (OA) patients. Since OA is a chronic condition requiring prolonged treatment, the long-term efficacy and safety of Meriva were investigated in a longer (eight months) study involving 100 OA patients. The clinical end points (Western Ontario and McMaster Universities [WOMAC] score, Karnofsky Performance Scale Index, and treadmill walking performance) were complemented by the evaluation of a series of inflammatory markers (interleukin [IL]-1beta, IL-6, soluble CD40 ligand [sCD40L], soluble vascular cell adhesion molecule (sVCAM)-1, and erythrocyte sedimentation rate [ESR]). This represents the most ambitious attempt, to date, to evaluate the clinical efficacy and safety of curcumin as an anti-inflammatory agent. Significant improvements of both the clinical and biochemical end points were observed for Meriva compared to the control group. This, coupled with an excellent tolerability, suggests that Meriva is worth considering for the long-term complementary management of osteoarthritis.
Knee osteoarthritis (OA) is a major cause of pain and functional limitation in older adults, yet longer-term studies of medical treatment of OA are limited.
To evaluate the efficacy and safety of glucosamine and chondroitin sulphate (CS), alone or in combination, as well as celecoxib and placebo on painful knee OA over 2 years.
A 24-month, double-blind, placebo-controlled study, conducted at nine sites in the US ancillary to the Glucosamine/chondroitin Arthritis Intervention Trial, enrolled 662 patients with knee OA who satisfied radiographic criteria (Kellgren/Lawrence grade 2 or 3 changes and baseline joint space width of at least 2 mm). This subset continued to receive their randomised treatment: glucosamine 500 mg three times daily, CS 400 mg three times daily, the combination of glucosamine and CS, celecoxib 200 mg daily, or placebo over 24 months. The primary outcome was a 20% reduction in Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain over 24 months. Secondary outcomes included an Outcome Measures in Rheumatology/Osteoarthritis Research Society International response and change from baseline in WOMAC pain and function.
Compared with placebo, the odds of achieving a 20% reduction in WOMAC pain were celecoxib: 1.21, glucosamine: 1.16, combination glucosamine/CS: 0.83 and CS alone: 0.69, and were not statistically significant.
Over 2 years, no treatment achieved a clinically important difference in WOMAC pain or function as compared with placebo. However, glucosamine and celecoxib showed beneficial but not significant trends. Adverse reactions were similar among treatment groups and serious adverse events were rare for all treatments.
Women often seek alternative treatment options such as herbs, dietary supplements, and vitamins and minerals to treat women's health issues across the lifespan. Women may use complementary and alternative supplements for dysmenorrhea, premenstrual syndrome, infertility, nausea and vomiting during pregnancy, and symptoms of menopause. In general, there is a deficit of well-designed, randomized, controlled trials to evaluate the efficacy and safety of complementary and alternative medicine for these indications, which makes it difficult to provide evidence-based recommendations. This review outlines the evidence for efficacy and safety that is currently available for dietary supplement use by women to manage health conditions specific to the female patient.
The objective of this study was to determine the efficacy and safety of Curcuma domestica extracts in pain reduction and functional improvement in patients with knee osteoarthritis.
The design and setting were a randomized controlled study at a university hospital in Bangkok, Thailand.
One-hundred and seven (107) patients with primary knee osteoarthritis (OA) with pain score of > or =5 were randomized to receive ibuprofen 800 mg per day or C. domestica extracts 2 g per day for 6 weeks. The main outcomes were improvement in pain on level walking, pain on stairs, and functions of knee assessed by time spent during 100-m walk and going up and down a flight of stairs. The adverse events were also recorded.
Fifty-two (52) and 55 patients were randomized to C. domestica extracts and ibuprofen groups, respectively. Baseline characteristics of the patients in both groups were not different. The mean scores of the aforementioned outcomes at weeks 0, 2, 4, and 6 were significantly improved when compared with the baseline values in both groups. There was no difference in those parameters between the patients receiving ibuprofen and C. domestica extracts, except pain on stairs (p = 0.016). No significant difference of adverse events between both groups was found (33.3% versus 44.2%, p = 0.36 in C. domestica extracts and ibuprofen groups, respectively).
C. domestica extracts seem to be similarly efficacious and safe as ibuprofen for the treatment of knee OA.
This report presents selected estimates of complementary and alternative medicine (CAM) use among U.S. adults and children, using data from the 2007 National Health Interview Survey (NHIS), conducted by the Centers for Disease Control and Prevention's (CDC) National Center for Health Statistics (NCHS). Trends in adult use were assessed by comparing data from the 2007 and 2002 NHIS.
Estimates were derived from the Complementary and Alternative Medicine supplements and Core components of the 2007 and 2002 NHIS. Estimates were generated and comparisons conducted using the SUDAAN statistical package to account for the complex sample design.
In 2007, almost 4 out of 10 adults had used CAM therapy in the past 12 months, with the most commonly used therapies being nonvitamin, nonmineral, natural products (17.7%) and deep breathing exercises (12.7%). American Indian or Alaska Native adults (50.3%) and white adults (43.1%) were more likely to use CAM than Asian adults (39.9%) or black adults (25.5%). Results from the 2007 NHIS found that approximately one in nine children (11.8%) used CAM therapy in the past 12 months, with the most commonly used therapies being nonvitamin, nonmineral, natural products (3.9%) and chiropractic or osteopathic manipulation (2.8%). Children whose parent used CAM were almost five times as likely (23.9%) to use CAM as children whose parent did not use CAM (5.1%). For both adults and children in 2007, when worry about cost delayed receipt of conventional care, individuals were more likely to use CAM than when the cost of conventional care was not a worry. Between 2002 and 2007 increased use was seen among adults for acupuncture, deep breathing exercises, massage therapy, meditation, naturopathy, and yoga. CAM use for head or chest colds showed a marked decrease from 2002 to 2007 (9.5% to 2.0%).
Maxepa contains eicosapentaenoic acid (EPA) (171 mg/capsule) and docosahexaenoic acid (DHA) (114 mg/capsule). EPA acts as an alternative substrate to arachidonate, leading to the formation of the less proinflammatory prostaglandins (‘3’ series) and leukotrienes (‘5’ series), If Maxepa has anti-inflammatory properties it could be expected to reduce the requirement for NSAIDs in patients with RA. This has not been investigated nor has Maxepa therapy been studied over a full 1–yr period.
Sixty-four patients with stable RA requiring NSAID therapy only were studied. Patients received either 10 Maxepa or air-filled placebo capsules per day for 12 months. All then received placebo capsules for a further 3 months. Patients were reviewed at 3-monthly intervals. NSAID requirement at entry visit for each patient was assigned as 100%. Patients were instructed to slowly reduce their NSAID dosage providing there was no worsening of their symptoms. Clinical and labora tory parameters of RA activity were also measured. There was a significant reduction in NSAID usage in patients on Maxepa when compared with placebo from month 3 [ (95% CI. for mean) requirement–71.1 (55.9–86.2)% and 89.7 (73.7—105.7)%, respectively]. This effect reached its maximum at month 12 [(24.5–56.6)% and 84.1 (62.7 – 105.5)%, respectively] and persisted to month 15 [(27.6–61.8)% and 85.8 (60.5–111.1)%, respectively] (P<0.001, ANOVA). These patients were able to reduce their NSAID requirement without experiencing any deterioration in the clinical and laboratory parameters of RA activity.
Seasonal allergic rhinitis (SAR) affects more than 23 million Americans annually, and current epidemiologic studies indicate that its prevalence within the United States is increasing. Numerous clinical observations and case studies have led researchers to hypothesize that methylsulfonylmethane (MSM) may help ameliorate the symptoms associated with SAR.
The primary goal of this study was to evaluate the efficacy of MSM in the reduction of SAR-associated symptoms. This study also examined possible adverse reactions associated with methylsulfonylmethane supplementation. Finally, this study attempted to elucidate the method of action by which MSM elicits its effect on allergy symptoms.
Fifty-five (55) subjects were recruited for the study. All met the criteria for participation in the study. 50 subjects completed the study. Those subjects completing the study consumed 2,600 mg of MSM orally per day for 30 days. Clinical respiratory symptoms and energy levels were evaluated by a Seasonal Allergy Symptom Questionnaire (SASQ) at baseline and on days 7, 14, 21, and 30. Immune and inflammatory reactions were measured by plasma immunoglobulin E (IgE) and C-reactive protein at baseline and on day 30. An additional inflammatory biomarker, plasma histamine, was measured in a subset of subjects (n = 5).
Day 7 upper and total respiratory symptoms were reduced significantly from baseline (p < 0.01 and p < 0.005, respectively). Lower respiratory symptoms were significantly improved from baseline by week 3 (p < 0.001). All respiratory improvements were maintained through the 30-day visit. Energy levels increased significantly by day 14 (p < 0.0001); this increase continued through day 30. No significant changes were observed in plasma IgE or histamine levels. The results of this study are promising. It would be worthwhile to conduct a larger, randomized, double-blind, placebo-controlled study to establish further if MSM would be a useful agent in the treatment of symptoms associated with SAR.
The results of this study suggest that MSM supplementation of 2,600 mg/day for 30 days may be efficacious in the reduction of symptoms associated with SAR. Furthermore, few side effects are associated with the use of this compound. Recent acute and subacute chronic toxicologic data on the same source of MSM as used in this study, further validate the safety of this product.
Conventional symptomatic treatments for osteoarthritis do not favorably affect disease progression. The aim of this randomized, placebo-controlled trial was to determine whether long-term (3-year) treatment with glucosamine sulfate can modify the progression of joint structure and symptom changes in knee osteoarthritis, as previously suggested.
Two hundred two patients with knee osteoarthritis (using American College of Rheumatology criteria) were randomized to receive oral glucosamine sulfate, 1500 mg once a day, or placebo. Changes in radiographic minimum joint space width were measured in the medial compartment of the tibiofemoral joint, and symptoms were assessed using the algo-functional indexes of Lequesne and WOMAC (Western Ontario and McMaster Universities).
Osteoarthritis was of mild to moderate severity at enrollment, with average joint space widths of slightly less than 4 mm and a Lequesne index score of less than 9 points. Progressive joint space narrowing with placebo use was -0.19 mm (95% confidence interval, -0.29 to -0.09 mm) after 3 years. Conversely, there was no average change with glucosamine sulfate use (0.04 mm; 95% confidence interval, -0.06 to 0.14 mm), with a significant difference between groups (P =.001). Fewer patients treated with glucosamine sulfate experienced predefined severe narrowings (>0.5 mm): 5% vs 14% (P =.05). Symptoms improved modestly with placebo use but as much as 20% to 25% with glucosamine sulfate use, with significant final differences on the Lequesne index and the WOMAC total index and pain, function, and stiffness subscales. Safety was good and without differences between groups.
Long-term treatment with glucosamine sulfate retarded the progression of knee osteoarthritis, possibly determining disease modification.
Patients with rheumatoid arthritis (RA) improve on a vegetarian diet or supplementation with fish oil. We investigated the effects of both dietary measures, alone and in combination, on inflammation, fatty acid composition of erythrocyte lipids, eicosanoids, and cytokine biosynthesis in patients with RA.
Sixty-eight patients with definitive RA were matched into two groups of 34 subjects each. One group was observed for 8 months on a normal western diet (WD) and the other on an anti-inflammatory diet (AID) providing an arachidonic acid intake of less than 90 mg/day. Patients in both groups were allocated to receive placebo or fish oil capsules (30 mg/kg body weight) for 3 months in a double-blind crossover study with a 2-month washout period between treatments. Clinical examination and routine laboratory findings were evaluated every month, and erythrocyte fatty acids, eicosanoids, and cytokines were evaluated before and after each 3-month experimental period.
Sixty patients completed the study. In AID patients, but not in WD patients, the numbers of tender and swollen joints decreased by 14% during placebo treatment. In AID patients, as compared to WD patients, fish oil led to a significant reduction in the numbers of tender (28% vs 11%) and swollen (34% vs 22%) joints (P<0.01). Compared to baseline levels, higher enrichment of eicosapentaenoic acid in erythrocyte lipids (244% vs 217%) and lower formation of leukotriene B(4) (34% vs 8%, P>0.01), 11-dehydro-thromboxane B(2) (15% vs 10%, P<0.05), and prostaglandin metabolites (21% vs 16%, P<0.003) were found in AID patients, especially when fish oil was given during months 6-8 of the experiment.
A diet low in arachidonic acid ameliorates clinical signs of inflammation in patients with RA and augments the beneficial effect of fish oil supplementation.
Harpagophytum procumbens (Pedaliaceae) has been used for the treatment of pain and arthritis. The effect of Harpagophytum procumbens against lipopolysaccharide-induced inflammation was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, reverse transcription-polymerase chain reaction, prostaglandin E(2) (PGE(2)) immunoassay, and nitric oxide detection on mouse fibroblast cell line L929. The aqueous extract of Harpagophytum procumbens was shown to suppress PGE(2) synthesis and nitric oxide production by inhibiting lipopolysaccharide-stimulated enhancement of the cyclooxygenase-2 and inducible nitric oxide synthase (iNOS) mRNAs expressions in L929 cells. These results suggest that Harpagophytum procumbens exerts anti-inflammatory and analgesic effects probably by suppressing cyclooxygenase-2 and iNOS expressions.
Human beings evolved consuming a diet that contained about equal amounts of n-3 and n-6 essential fatty acids. Over the past 100-150 y there has been an enormous increase in the consumption of n-6 fatty acids due to the increased intake of vegetable oils from corn, sunflower seeds, safflower seeds, cottonseed, and soybeans. Today, in Western diets, the ratio of n-6 to n-3 fatty acids ranges from ≃20-30:1 instead of the traditional range of 1- 2:1. Studies indicate that a high intake of n-6 fatty acids shifts the physiologic state to one that is prothrombotic and proaggregatory, characterized by increases in blood viscosity, vasospasm, and vasoconstriction and decreases in bleeding time. n-3 Fatty acids, however, have antiinflammatory, antithrombotic, antiarrhythmic, hypolipidemic, and vasodilatory properties. These beneficial effects of n-3 fatty acids have been shown in the secondary prevention of coronary heart disease, hypertension, type 2 diabetes, and, in some patients with renal disease, rheumatoid arthritis, ulcerative colitis, Crohn disease, and chronic obstructive pulmonary disease. Most of the studies were carried out with fish oils [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)]. However, α-linolenic acid, found in green leafy vegetables, flaxseed, rapeseed, and walnuts, desaturates and elongates in the human body to EPA and DHA and by itself may have beneficial effects in health and in the control of chronic diseases.
Abdominal pain is common in the general population and, in patients with irritable bowel syndrome, is attributed to visceral hypersensitivity. We found that oral administration of specific Lactobacillus strains induced the expression of mu-opioid and cannabinoid receptors in intestinal epithelial cells, and mediated analgesic functions in the gut-similar to the effects of morphine. These results suggest that the microbiology of the intestinal tract influences our visceral perception, and suggest new approaches for the treatment of abdominal pain and irritable bowel syndrome.
Background:
Fibromyalgia is a syndrome characterized by chronic pain, fatigue, depression, and sleep disturbances. Its primary cause is unclear. Several studies have reported decreased intracellular magnesium levels in patients with fibromyalgia and have found negative correlation between magnesium levels and fibromyalgia symptoms.
Objective:
To gather preliminary data on whether transdermal magnesium can improve quality of life for women who have fibromyalgia.
Design, setting, participants and interventions:
This is a patient questionnaires and survey in a fibromyalgia clinic at a tertiary medical center. Forty female patients with the diagnosis of fibromyalgia were enrolled. Each participant was provided a spray bottle containing a transdermal magnesium chloride solution and asked to apply 4 sprays per limb twice daily for 4 weeks. Participants were asked to complete the Revised Fibromyalgia Impact Questionnaire, SF-36v2 Health Survey, and a quality-of-life analog scale at baseline, week 2, and week 4.
Main outcome measure:
Questionnaire and survey scores, evaluated through intent-to-treat and per-protocol analyses.
Results:
Twenty-four patients completed the study (mean [SD] age, 57.2 [7.6] years; white, 95%; mean body mass index, 31.3 kg/m(2)). With intention-to-treat analysis, Revised Fibromyalgia Impact Questionnaire subscale and total scores were significantly improved at week 2 and week 4 (total score, P = 0.001). Per-protocol analysis results were similar: all subscales of the Revised Fibromyalgia Impact Questionnaire were significantly improved at week 2 and week 4 (total score, P = 0.001).
Conclusion:
This pilot study suggests that transdermal magnesium chloride applied on upper and lower limbs may be beneficial to patients with fibromyalgia.
Trial registration:
ClinicalTrials.gov.ldentifier NCT01968772.
Willow bark extract has been used for thousands of years as an anti-inflammatory, antipyretic, and analgesic. In spite of its long history of use, relatively few human and animal studies have been published that confirm anecdotal observations. A small number of clinical studies have been conducted that support the use of willow bark extracts in chronic lower back and joint pain and osteoarthritis. Willow bark extracts also are widely used in sports performance and weight loss products presumably because of anti-inflammatory and analgesic activities, although no human studies have been published that specifically and directly document beneficial effects. In recent years, various in vitro and animal studies have demonstrated that the anti-inflammatory activity of willow bark extract is associated with down regulation of the inflammatory mediators tumor necrosis factor-α and nuclear factor-kappa B. Although willow bark extracts are generally standardized to salicin, other ingredients in the extracts including other salicylates as well as polyphenols, and flavonoids may also play prominent roles in the therapeutic actions. Adverse effects appear to be minimal as compared to non-steroidal anti-inflammatory drugs including aspirin. The primary cause for concern may relate to allergic reactions in salicylate-sensitive individuals. Copyright © 2015 John Wiley & Sons, Ltd.
Copyright © 2015 John Wiley & Sons, Ltd.
Neuropathic pain is caused by disease or injury of the nervous system and includes various chronic conditions that, together, affect up to 8% of the population. A substantial body of neuropathic pain research points to several important contributory mechanisms including aberrant ectopic activity in nociceptive nerves, peripheral and central sensitization, impaired inhibitory modulation, and pathological activation of microglia. Clinical evaluation of neuropathic pain requires a thorough history and physical examination to identify characteristic signs and symptoms. In many cases, other laboratory investigations and clinical neurophysiological testing may help identify the underlying etiology and guide treatment selection. Available treatments essentially provide only symptomatic relief and may include nonpharmacological, pharmacological, and interventional therapies. Most extensive evidence is available for pharmacological treatment, and currently recommended first-line treatments include antidepressants (tricyclic agents and serotonin-norepinephrine reuptake inhibitors) and anticonvulsants (gabapentin and pregabalin). Individualized multidisciplinary patient care is facilitated by careful consideration of pain-related disability (eg, depression and occupational dysfunction) as well as patient education; repeat follow-up and strategic referral to appropriate medical/surgical subspecialties; and physical and psychological therapies. In the near future, continued preclinical and clinical research and development are expected to lead to further advancements in the diagnosis and treatment of neuropathic pain.
Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
Background:
Structure-modifying medications or nutraceuticals may be an effective treatment for osteoarthritis. This study identified 12 treatments that may possess chondroprotective properties: oral glucosamine; chondroitin; nonsteroidal anti-inflammatory drugs (NSAIDs); polyunsaturated fatty acids; S-adenosylmethionine; avocado and soybean unsaponifiable fractions; methylsulfonylmethane; vitamins C, D, and E; intra-articular injections of hyaluronic acid; and platelet-rich plasma (PRP).
Purpose:
To perform a systematic review of randomized controlled trials for the effectiveness of each agent in preserving articular cartilage of the knee and delaying the progression of osteoarthritis.
Study design:
Systematic review; Level of evidence, 2.
Methods:
A literature search was performed using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Searches were performed using "treatment," "osteoarthritis," and "knee" as keywords. Selection criteria included randomized controlled trials of ≥12 months, with a placebo control, measuring radiographic changes in joint space width, cartilage volume, or radiographic progression of osteoarthritis. The primary outcome was changes in joint integrity measures.
Results:
A total of 3514 studies were identified from the initial search, 13 of which met inclusion criteria. Treatment with chondroitin sulfate showed a significant reduction in cartilage loss in 3 of 4 studies identified compared with placebo. Two of 3 trials identified for glucosamine also reported significant structural effects relative to placebo. Intra-articular hyaluronic acid was effective in lowering the rate of cartilage loss in only 1 of 3 studies identified versus placebo. Of the 6 studies identified for NSAIDs, vitamin E, and vitamin D, none showed any structural effect compared with placebo. No studies were found that met the inclusion criteria for polyunsaturated fatty acids, S-adenosylmethionine, avocado and soybean unsaponifiable fractions, methylsulfonylmethane, vitamin C, or PRP.
Conclusion:
For patients with or at risk for osteoarthritis, the use of glucosamine and chondroitin sulfate may serve as a nonoperative means to protect joint cartilage and delay osteoarthritis progression. Hyaluronic acid injections showed variable efficacy, while NSAIDs and vitamins E and D showed no effect on osteoarthritis progression. The other agents evaluated had no evidence in the literature to support or refute their use for chondroprotection.
Statins are the treatment of choice for dyslipidemia, primarily lowering elevated LDL-C levels and reducing the occurrence of major cardiovascular events. In June 2011, the Food and Drug Administration issued a warning regarding the use of high-dose simvastatin 80 mg and its risk of myopathy.
The incidence of myalgia, myopathy, and rhabdomyolysis was analyzed in a veteran population prescribed simvastatin 80 mg. Risk factors for myalgia were examined and compared with the results of recently published studies.
This was a retrospective medical record review of 450 patients who were prescribed simvastatin 80 mg at the Veterans Affairs Western New York Healthcare System between August 1, 2006, and July 31, 2011. Records were examined for evidence of myalgia, myopathy (incipient or definite), and rhabdomyolysis. Variables that may have contributed to the development of myalgia were also collected and analyzed.
Myalgia was reported by 50 patients (11.1%), whereas rhabdomyolysis developed in 1 patient (0.22%). No patient fit the criteria for myopathy (incipient or definite). Myalgia was statistically more likely to occur in younger patients, patients with a history of myalgia, and patients with low vitamin D levels. The mean (SD) vitamin D level in patients experiencing myalgia was 26.2 (12.9) versus 36.3 (11.8) ng/mL. The 25-hydroxyvitamin D level in those who reported myalgia was approximately 10 ng/mL lower compared with those who tolerated simvastatin 80 mg (P = 0.0003). There was no statistically significant association between length of therapy and development of myalgia.
A lower incidence of adverse muscle events with high-dose simvastatin 80 mg was found in patients with higher vitamin D levels, suggesting that correction of 25-hydroxyvitamin D levels before statin therapy initiation may mitigate one risk factor in the development of statin-related myalgia. Vitamin D insufficiency appears to be a risk factor for the development of myalgia.
The role of calcifediol in the perception of chronic pain is a widely discussed subject. Low serum levels of calcifediol are especially common in patients with severe pain and fibromyalgia syndrome (FMS). We lack evidence of the role of vitamin D supplementation in these patients. To our knowledge, no randomized controlled trial has been published on the subject. Thirty women with FMS according to the 1990 and 2010 American College of Rheumatology criteria, with serum calcifediol levels <32ng/mL (80nmol/L), were randomized to treatment group (TG) or control group (CG). The goal was to achieve serum calcifediol levels between 32 and 48ng/mL for 20weeks via oral supplementation with cholecalciferol. The CG received placebo medication. Re-evaluation was performed in both groups after a further 24weeks without cholecalciferol supplementation. The main hypothesis was that high levels of serum calcifediol should result in a reduction of pain (visual analog scale score). Additional variables were evaluated using the Short Form Health Survey 36, the Hospital Anxiety and Depression Scale, the Fibromyalgia Impact Questionnaire, and the Somatization subscale of Symptom Checklist-90-Revised. A marked reduction in pain was noted over the treatment period in TG: a 2 (groups)×4 (time points) variance analysis showed a significant group effect in visual analog scale scores. This also was correlated with scores on the physical role functioning scale of the Short Form Health Survey 36. Optimization of calcifediol levels in FMS had a positive effect on the perception of pain. This economical therapy with a low side effect profile may well be considered in patients with FMS. However, further studies with larger patient numbers are needed to prove the hypothesis.
Study objective:
Efficacy and safety of willow bark extract for pain reduction in patients suffering from musculoskeletal disorders (MSD) has been shown in clinical short term trials. Therefore this observational study over 6 months should evaluate patterns of treatments like mono- or combinations therapy, dosage and safety during long-term treatment under pragmatic conditions with the aqueous willow bark extract STW 33-I, (Proaktiv(®); drug-extract-ratio 16-23:1).
Patients and methods:
The patients were treated with STW 33-I; comedication with other NSAIDs and opioids was allowed. An extensive case report form including pain questionnaires and patient diary was used for outcome evaluation.
Results:
Four hundred and thirty-six patients with rheumatic pain mainly due to osteoarthritis (56.2%) and back pain (59.9%) were included. During the study the mean reductions from baseline value 58.4±22.6-31.8±22.5 after 24 weeks in the pain intensity scale (VAS 0-100mm) were significant even after 3 weeks with a reduction by 26 mm (45.6% of the baseline value) at the end of the study. The relative reductions of the weekly means of the daily patient self-rated scores of the pain (6-point Likert-scales) were between 33% and 44% of the baseline values during the course of the study. We present results of subgroups according their analgetic/antiphlogistic comedication. The distribution and specification of the main adverse events and the ratings of the treatment showed a good tolerability. No relevant drug interactions were reported.
Conclusion:
These data suggest that STW 33-I can be used as a basic treatment in the long-term therapy of painful musculoskeletal disorders and that it can be combined with NSAIDs and opioids if necessary.
Hypovitaminosis D in the elderly causes falls and fractures as a result of impaired neuromuscular functions and also may be a reason for nonspecific musculosceletal pain. The aim of this study is to investigate the benefits of a single dose per os or parenterally administrated vitamin D on increasing the quality of life and functional mobility and decreasing the pain in the elderly. The community-dwelling elderly subjects over 65 years age were included in the study. The subjects were given 300.000 IU Vitamin D via per os and parenteral route and assessed after 4 weeks. The serum creatinine, calcium, phosphorous, ALT, ALP, 24-h urine calcium excretion, PTH, and vitamin D levels, as well as VAS (visual analog scale) for pain assessment, functional mobility with TUG (timed up and go test) and quality of life with SF-36 before and after the treatment were evaluated. The serum vitamin D levels were measured by the RIA method. The subjects were divided into four groups each consisting of 30 subjects. The 1st group took i.m. vitamin D, the 2nd group took i.m. placebo, the 3rd group took p.o. vitamin D, and the 4th group took p.o. placebo. The mean age of all the participants was 70.1 ± 4.3 years. There was no difference in the age and gender between the groups (P > 0.05). After treatment, the PTH level of first group was decreased (P = 0.0001) and the vitamin D level increased (P = 0.0001) significantly. In the third group, the PTH level of first group was decreased (P = 0.0001) and the vitamin D level increased (P = 0.004) and the 24-h calcium excretion in urine (P = 0.015) increased significantly. When the pain, the functional mobility, and the quality of life were evaluated, in the first group, the TUG (P = 0.0001) and the VAS (P = 0.0001) decreased significantly, whereas the SF-36 subtitles: physical functioning (P = 0.0001), role physical (0.006), bodily pain (P = 0.0001), general health (P = 0.007), social functioning (P = 0.05), and mental health (P = 0.048) increased significantly. In group two, the VAS (P = 0.001) decreased, the role physical (P = 0.009), and role emotional (P = 0.034) increased significantly; In group three, the TUG (P = 0.0001) and the VAS (P = 0.002) decreased, whereas the physical function (P = 0.0001) and role physical (0.001) increased significantly; In group four, the VAS (P = 0.007) decreased significantly. The megadose vitamin D administration increases quality of life, decreases pain, and improves functional mobility via po or im route in the elderly.
The use of both over-the-counter and prescription nonsteroidal medications is frequently recommended in a typical neurosurgical practice. But persistent long-term use safety concerns must be considered when prescribing these medications for chronic and degenerative pain conditions. This article is a literature review of the biochemical pathways of inflammatory pain, the potentially serious side effects of nonsteroidal drugs and commonly used and clinically studied natural alternative anti-inflammatory supplements. Although nonsteroidal medications can be effective, herbs and dietary supplements may offer a safer, and often an effective, alternative treatment for pain relief, especially for long-term use.
The authors used the blind method for evaluation of the morphological picture of the joints and the level of circulating immune complexes to study the effect of prolonged oral administration of dimethyl sulfoxide (DMSO) and its main metabolite dimethyl sulfone on the development of spontaneous arthritis in 36 Mrl/Mn/lnr female mice. It was found that DMSO and dimethyl sulfone lessen the destructive changes in the joints, while DMSO also inhibits the manifestation of immune disorders, i. e. produces a "basal" effect on the course of spontaneous chronic arthritis in experimental animals.
Twenty-four patients (9 M and 15 F, age range 51-82) with polymyalgia rheumatica receiving 6-methylprednisolone for a period of 9 months (16 mg/daily/two weeks, 14 mg/daily/two weeks, 12 mg/daily/1 month, 10 mg/daily/1 month, 8 mg/daily/1 month, 6 mg/daily/1 month and 4 mg/daily for the last four months) were randomly assigned to receive either 250HD3 (35 mcg/day for 25 days/month) (Group A) or placebo (Group B) in a double-blind study. All patients also received 500 mg elemental calcium daily. Before and at 3, 6 and 9 months ESR, tenderness on palpation and subjective pain were evaluated. At the same times, mineral metabolism parameters (serum calcium, phosphorus, alkaline phosphatase, 24-h urinary calcium, phosphate and 24-h hydroxyproline excretion) and radial bone mineral content (BMC) were evaluated. Activity indexes (ESR and clinical parameters) improved in both groups. Furthermore, serum alkaline phosphatase and 24-h hydroxyproline excretion decreased significantly only in Group A, and BMC decreased significantly in Group B but rose slightly in Group A. No side effects were observed in any of the patients.
To study the long-term effects of supplementation with omega-3 fatty acids (omega 3) in patients with active rheumatoid arthritis.
Ninety patients were enrolled in a 12-month, double-blind, randomized study comparing daily supplementations with either 2.6 gm of omega 3, or 1.3 gm of omega 3 + 3 gm of olive oil, or 6 gm of olive oil.
Significant improvement in the patient's global evaluation and in the physician's assessment of pain was observed only in those taking 2.6 gm/day of omega 3. The proportions of patients who improved and of those who were able to reduce their concomitant antirheumatic medications were significantly greater with 2.6 gm/day of omega 3.
Daily supplementation with 2.6 gm of omega 3 results in significant clinical benefit and may reduce the need for concomitant antirheumatic medication.
The medicinal system of the Asháninka Indians in Perú is portrayed. Three categories of medical disorders and healers are recognized. A human is viewed to consist of a physical and a spiritual being who communicate with each other by means of a regulating element. The significance of Uncaria tomentosa (Willd.) DC. (Rubiaceae), locally known as unã de gato, in traditional medicine is emphasized by its exclusive use by priests to influence this regulation. Pharmacological and toxicological results obtained with extracts or isolated compounds are summarized. Pentacyclic oxindole alkaloids stimulate endothelial cells in vitro to produce a lymphocyte-proliferation-regulating factor. Tetracyclic oxindole alkaloids act as antagonists. A significant normalization of lymphocyte percentage was observed in vivo although total leucocyte numbers did not change.
Postanaesthesia care units used to echo with cries of patients in pain after general anaesthesia. Each as-needed dose of analgesia was given only after permission of the surgeon or anaesthesiologist. Once conscious, patients were required to request each subsequent analgesic dose until hospital discharge. Not surprisingly, nearly half the patients who have an operation experience moderate to severe pain after surgery. Acute pain control has advanced dramatically and is now a field with dedicated texts, journals, and research. Despite improved surgical techniques that have transformed many operations into same-day procedures, inadequately controlled pain may still extend the length of hospital stay and predispose to expensive, time-consuming complications such as pneumonia. Recognition of economic and humanitarian benefits of pain control has prompted worldwide attention from professional groups, insurers, and governments. This paper describes the process of acute pain and measures to control it with drugs or non-pharmacological interventions. Even brief intervals of acute pain can induce long-term neuronal remodelling and sensitisation ("plasticity"), chronic pain, and lasting psychologial distress. Hence, acute pain and other types of pain (cancer-related or chronic) that are classified as distinct actually have many similarities.
Herbal medicines are widely used for the treatment of pain, although there is not much information on their effectiveness. This study was designed to evaluate the effectiveness of willow (Salix) bark extract, which is widely used in Europe, for the treatment of low back pain.
We enrolled 210 patients with an exacerbation of chronic low back pain who reported current pain of 5 or more (out of 10) on a visual analog scale. They were randomly assigned to receive an oral willow bark extract with either 120 mg (low dose) or 240 mg (high dose) of salicin, or placebo, with tramadol as the sole rescue medication, in a 4-week blinded trial. The principal outcome measure was the proportion of patients who were pain-free without tramadol for at least 5 days during the final week of the study.
The treatment and placebo groups were similar at baseline in 114 of 120 clinical features. A total of 191 patients completed the study. The numbers of pain-free patients in the last week of treatment were 27 (39%) of 65 in the group receiving high-dose extract, 15 (21%) of 67 in the group receiving low-dose extract, and 4 (6%) of 59 in the placebo group (P <0.001). The response in the high-dose group was evident after only 1 week of treatment. Significantly more patients in the placebo group required tramadol (P <0.001) during each week of the study. One patient suffered a severe allergic reaction, perhaps to the extract.
Willow bark extract may be a useful and safe treatment for low back pain.
In a double-blind, randomized, multicentre clinical study, the efficacy and tolerance of a herbal medicine product, Harpadol (6 capsules/day, each containing 435 mg of powdered cryoground powder Harpagophytum procumbens), was compared with diacerhein 100 mg/day in the treatment, for 4 months, of 122 patients suffering from osteoarthritis of the knee and hip. Assessments of pain and functional disability were made on a 10 cm horizontal visual analogue scale; severity of osteoarthritis was evaluated by Lequesne's index. Spontaneous pain showed a significant improvement during the course of the study and there was no difference in the efficacy of the two treatments. Similarly, there was a progressive and significant reduction in the Lequesne functional index and no statistical difference was found between Harpadol and diacerhein. At completion of the study, patients taking Harpadol were using significantly less NSAIDs and antalgic drugs. The frequency of adverse events was significantly lower in the Harpadol group. The most frequent event reported was diarrhea, occurring in 8.1% and 26.7% of Harpadol and diacerhein patients respectively. The global tolerance assessment by patients at the end of treatment favoured Harpadol. The results of this study demonstrate that Harpadol is comparable in efficacy and superior in safety to diacerhein.
This study assessed the clinical efficacy of a chemically standardized willow bark extract in the treatment of osteoarthritis. Willow bark extract, in a dose corresponding to 240 mg salicin/day, was compared with placebo in a 2-week, double-blind, randomized controlled trial. The primary outcome measure was the pain dimension of the WOMAC Osteoarthritis Index. Secondary outcome measures included the stiffness and physical function dimensions of the WOMAC, daily visual analogue scales (VAS) on pain and physical function, and final overall assessments by both patients and investigators. A total of 78 patients (39 willow bark extract, 39 placebo) participated in the trial. A statistically significant difference between the active treatment and the placebo group was observed in the WOMAC pain dimension (d = 6.5 mm, 95% C.I. = 0.2-12.7 mm, p = 0.047); the WOMAC pain score was reduced by 14% from the baseline level after 2 weeks of active treatment, compared with an increase of 2% in the placebo group. The patient diary VAS confirmed this result, and likewise the final overall assessments showed superiority of the willow bark extract over the placebo (patients' assessment, p = 0.0002; investigators' assessment, p = 0.0073). It is concluded that the willow bark extract showed a moderate analgesic effect in osteoarthritis and appeared to be well tolerated.
Besides checking estimates of effectiveness and safety of using the proprietary Harpagophytum extract Doloteffin, this postmarketing surveillance compared various disease-specific* and generic** measures of effect. We enrolled 250 patients suffering from nonspecific low back pain (Back group: n = 104) or osteoarthritic pain in the knee (Knee group: n = 85) or hip (Hip group: n = 61). They took an 8-week course of Doloteffin at a dose providing 60 mg harpagoside per day. The measures of effect on pain and disability included the percentage changes from baseline of established instruments (Arhus low back pain index*, WOMAC index*, German version of the HAQ**) and unvalidated measures (total pain index*, three score index*, the patient's global assessment** of the effectiveness of treatment). Patients also received a diary for the daily recording of their pain and any additional treatments for it. The three groups differed in age, weight and characteristics of initial pain. 227 patients completed the study. Multivariate analysis confirmed that several dimensions of effect were recorded by the several outcome measures but, in all groups, both the generic and disease-specific outcome measures improved by week 4 and further by 8. In multivariable analysis, the improvement tended to be more when the initial pain and disability score was more: older patients tended to improve less than younger, the hip group tended to improve convincingly more than the back group, whereas the improvement in the knee group was less readily differentiated from that in the back group. The subgroup of Back patients who required NSAIDs during the 8 weeks used significantly more per patient than patients in the other two groups, but that requirement also declined more with time. About 10% of the patients suffered from minor adverse events that could possibly have been attributable to Doloteffin. Between 50% and 70% of the patients benefitted from Doloteffin with few adverse effects. Thus, Doloteffin is well worth considering for osteoarthritic knee and hip pain and nonspecific low back pain.
To assess whether, in children, oral magnesium oxide reduces migrainous headache frequency, severity, and associated features compared to placebo.
There is no single, safe, widely well-tolerated, and effective prophylactic treatment for all children and adolescents with frequent migrainous headache.
Randomized, double-blind, placebo-controlled, parallel-group trial.
This study was conducted between June 1997 and January 2000 using 7 selected Northern California Kaiser Permanente sites. We recruited children of ages 3 to 17 years who reported a 4-week history of at least weekly, moderate-to-severe headache with a throbbing or pulsatile quality, associated anorexia/nausea, vomiting, photophobia, sonophobia, or relief with sleep, but no fever or evidence of infection. Subjects were randomly assigned to receive either magnesium oxide (9 mg/kg per day by mouth divided 3 times a day with food) (n = 58) or matching placebo (n = 60) for 16 weeks. The number of headache days (days with at least one headache) during each of eight 2-week intervals was chosen to be the primary outcome variable.
Of those enrolled, 86 (73%) completed the study (42 received magnesium oxide and 44 placebo); 74 of 192 eligible subjects declined to participate. Baseline information on demographic factors, health status, and headache history was similar comparing the 2 groups. By intention-to-treat analysis, we found a statistically significant decrease over time in headache frequency in the magnesium oxide group (P =.0037) but not in the placebo group (P =.086), although the slopes of these 2 lines were not statistically significantly different from each other (P =.88). The group treated with magnesium oxide had significantly lower headache severity (P =.0029) relative to the placebo group.
This study does not unequivocally determine whether oral magnesium oxide is or is not superior to placebo in preventing frequent migrainous headache in children, but treatment with the active agent did lead to a significant reduction in headache days. Larger trials involving this safe, appealing complementary therapy are needed.
Between 40% and 60% of Americans use complementary and alternative medicine to manage medical conditions, prevent disease, and promote health and well-being. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been used to treat joint pain associated with several inflammatory conditions. We conducted a meta-analysis of 17 randomized, controlled trials assessing the pain relieving effects of omega-3 PUFAs in patients with rheumatoid arthritis or joint pain secondary to inflammatory bowel disease and dysmenorrhea. Meta-analysis was conducted with Cochrane Review Manager 4.2.8. for six separate outcomes using standardized mean differences (SMDs) as a measure of effect size: (1) patient assessed pain, (2) physician assessed pain, (3) duration of morning stiffness, (4) number of painful and/or tender joints, (5) Ritchie articular index, and (6) nonselective nonsteroidal anti-inflammatory drug consumption. Supplementation with omega-3 PUFAs for 3-4 months reduces patient reported joint pain intensity (SMD: -0.26; 95% CI: -0.49 to -0.03, p=0.03), minutes of morning stiffness (SMD: -0.43; 95% CI: -0.72 to -0.15, p=0.003), number of painful and/or tender joints (SMD: -0.29; 95% CI: -0.48 to -0.10, p=0.003), and NSAID consumption (SMD: -0.40; 95% CI: -0.72 to -0.08, p=0.01). Significant effects were not detected for physician assessed pain (SMD: -0.14; 95% CI: -0.49 to 0.22, p=0.45) or Ritchie articular index (SMD: 0.15; 95% CI: -0.19 to 0.49, p=0.40) at 3-4 months. The results suggest that omega-3 PUFAs are an attractive adjunctive treatment for joint pain associated with rheumatoid arthritis, inflammatory bowel disease, and dysmenorrhea.
Objective:
Glucosamine, classified as a slow-acting drug in osteoarthritis (SADOA), is an efficacious chondroprotective agent. Methylsulfonylmethane (MSM), the isoxidised form of dimethyl-sulfoxide (DSMO), is an effective natural analgesic and anti-inflammatory agent. The aim of this study was to compare the efficacy and safety of oral glucosamine (Glu), methylsulfonylmethane (MSM), their combination and placebo in osteoarthritis of the knee.
Patients and design:
A total of 118 patients of either sex with mild to moderate osteoarthritis were included in the study and randomised to receive either Glu 500mg, MSM 500mg, Glu and MSM or placebo capsules three times daily for 12 weeks. Patients were evaluated at 0 (before drug administration), 2, 4, 8 and 12 weeks post-treatment for efficacy and safety. The efficacy parameters studied were the pain index, the swelling index, visual analogue scale pain intensity, 15m walking time, the Lequesne index, and consumption of rescue medicine.
Results:
Glu, MSM and their combination significantly improved signs and symptoms of osteoarthritis compared with placebo. There was a statistically significant decrease in mean (+/- SD) pain index from 1.74 +/- 0.47 at baseline to 0.65 +/- 0.71 at week 12 with Glu (p < 0.001). MSM significantly decreased the mean pain index from 1.53 +/- 0.51 to 0.74 +/- 0.65, and combination treatment resulted in a more significant decrease in the mean pain index (1.7 +/- 0.47 to 0.36 +/- 0.33; p < 0.001). After 12 weeks, the mean swelling index significantly decreased with Glu and MSM, while the decrease in swelling index with combination therapy was greater (1.43 +/- 0.63 to 0.14 +/- 0.35; p < 0.05) after 12 weeks. The combination produced a statistically significant decrease in the Lequesne index. All treatments were well tolerated.
Conclusion:
Glu, MSM and their combination produced an analgesic and anti-inflammatory effect in osteoarthritis. Combination therapy showed better efficacy in reducing pain and swelling and in improving the functional ability of joints than the individual agents. All the treatments were well tolerated. The onset of analgesic and anti-inflammatory activity was found to be more rapid with the combination than with Glu. It can be concluded that the combination of MSM with Glu provides better and more rapid improvement in patients with osteoarthritis.
To investigate the efficacy and tolerability of a 3-month duration, twice a-year, intermittent treatment with oral chondroitin sulfate (CS) in knee osteoarthritis (OA) patients.
A total of 120 patients with symptomatic knee OA were randomized into two groups receiving either 800mg CS or placebo (PBO) per day for two periods of 3 months during 1 year. Primary efficacy outcome was Lequesne's algo-functional index (AFI); secondary outcome parameters included VAS, walking time, global judgment, and paracetamol consumption. Radiological progression was assessed by automatic measurement of medial femoro-tibial joint space width on weight-bearing X-rays of both knees. Clinical and biological tolerability was assessed.
One hundred and ten of 120 patients were included in the ITT analysis. AFI decreased significantly by 36% in the CS group after 1 year as compared to 23% in the PBO group. Similar results were found for the secondary outcomes parameters. Radiological progression at month 12 showed significantly decreased joint space width in the PBO group with no change in the CS group. Tolerability was good with only minor adverse events identically observed in both groups.
This study provides evidences that oral CS decreased pain and improved knee function. The 3-month intermittent administration of 800mg/day of oral CS twice a year does support the prolonged effect known with symptom-modifying agents for OA. The inhibitory effect of CS on the radiological progression of the medial femoro-tibial joint space narrowing could suggest further evidence of its structure-modifying properties in knee OA.
Vitamin D intoxication associated with an over-the-counter supplement
- Koutkia