Anne Estrup Olesen

Aalborg University Hospital · Department of Internal Medicine

Introduction: Paracetamol poisoning is a frequent cause of hospitalization in Denmark. On 30 September 2013, the Danish authorities restricted packages available without a prescription in pharmacy outlets to contain a maximum of 10 g of paracetamol. We aimed to investigate the effects of this regulation. Methods: This was a cross-sectional study...

Medication reviews focusing on deprescribing can reduce potentially inappropriate medication; however, evidence regarding the effects on health-related outcomes is scares. In a real-life, quality improvement project, we aimed to investigate how a general practitioner-led medication review intervention with focus on deprescribing affected health-rel...

Evidence and gap maps (EGM) can be used to identify gaps within specific research areas and help guide future research agendas and directions. Currently, there are no EGMs within the broad domain of chronic musculoskeletal (MSK) pain in adults. The aim of this study was to create a contemporary EGM of interventions and outcomes used for research in...

Introduction Biologic therapy is widely used for inflammatory bowel disease (IBD) and may decrease surgery rates. However, it remains uncertain if there is unwarranted geographic variation in access to biologic therapy. The aim of the study was to explore if all patients had equal access to biologic therapy in the North Denmark Region. Methods A c...

Introduction: The high prevalence of chronic medical conditions among older adults leads to an increased use of prescription medications and a heightened risk of polypharmacy, raising the risk of falls and fractures. Psychotropic medications influence balance, and therefore our aim was to describe the use of psychotropic medications and the associ...

Objectives Patient and stakeholder engagements in research have increasingly gained attention in healthcare and healthcare-related research. A common and rigorous approach to establish research priorities based on input from people and stakeholders is the James Lind Alliance Priority Setting Partnership (JLA-PSP). The aim of this study was to estab...

Background: Musculoskeletal (MSK) pain is one of the most common reasons for consulting the general practitioner (GP) who can provide several treatments for managing MSK pain. One treatment option is pain medication. The aim of the present study was to explore the GPs’ attitudes towards: 1) management of MSK pain; 2) prescription of pain medication...

Background: In recent decades, navigation in modern healthcare has become increasingly difficult. Since the 1970s, the term health literacy (HL), defined as an individual’s ability to access, understand, appraise, and apply health information, has been increasingly used in the field of health science. Research indicates that low HL may interfere wi...

Background: Duloxetine is indicated in the management of pain in osteoarthritis. Evidence suggests that duloxetine modulate central pain mechanisms and cognitive factors, and these factors are assumed contributing to the analgesic effect. This proof-of-mechanism, randomized, placebo-controlled, crossover, double-blinded trial evaluated the effect...

Background The global burden of osteoarthritis (OA) is steadily increasing due to demographic and lifestyle changes. The nervous system can undergo peripheral and central neuroplastic changes (sensitization) in patients with OA impacting the options to manage the pain adequately. As a result of sensitization, patients with OA show lower pressure pa...

Background Patient and stakeholder engagements in research have increasingly gained attention in healthcare and healthcare-related research. A common and rigorous approach to establish research priorities based on input from people and stakeholders is the James Lind Alliance Priority Setting Partnership (JLA-PSP). The aim of this study was to estab...

Knowledge about current trends and epidemiology in poisonings is important to maintain quality in diagnostics, treatment, and prevention. We performed a cross-sectional study of all cases (n=261) admitted with drug poisoning to Aalborg University Hospital during one year in 2017-2018. Median age was 30 [22-49] years, and 58% were female. Fifty % we...

Objectives Musculoskeletal pain is common among children and adolescents. Despite the lack of evidence regarding harms and benefits, musculoskeletal pain is often managed with pain medication. The aim of this systematic review is to assess the prevalence of pain medication use for musculoskeletal pain among children and adolescents and the factors...

The physiological changes following Roux-en-Y gastric bypass (RYGB) surgery may impact drug release from mechanistically different controlled-release tablets, making generic substitution inappropriate. This study aimed to characterise the pharmacokinetic-pharmacodynamic relationships of oxycodone from a lipid-based and water-swellable controlled-re...

Background Short bowel syndrome is a disorder with several complications such as malnutrition and failure of drug therapy. Treatment with opioids is needed in many patients, and oral medication is preferred. However, optimal dosing is a difficult task as current guidelines are based on an intact gastrointestinal tract. Hence, the aim of this explor...

Moderate to severe pain is often treated with opioids, but central mechanisms underlying opioid analgesia are poorly understood. Findings thus far have been contradictory and none could infer opioid specific effects. This placebo-controlled, randomized, 2-way cross-over, double-blinded study aimed to explore opioid specific effects on central proce...

Introduction All Danish citizens aged >70 years are recommended to take vitamin D supplements. We hypothesized that renal insufficiency may impair the activation and effect of vitamin D supplements. We aimed to investigate the association between use of vitamin D supplements, and levels of 25-hydroxy-vitamin D and parathyroid hormone (PTH) in elder...

Background Studies investigating the underlying pathophysiology are needed to help explain and understand the postoperative complications following Roux-en-Y gastric bypass (RYGB) surgery. This study aimed to characterize segmental gastrointestinal pH profiles, motility measures, and transit times in patients with RYGB.Materials and Methods Ninetee...

Pain medication use for musculoskeletal pain among children: prevalence and associated factors Conclusions and future perspectives The use of pain medication for MSK pain is common in children and adolescents and higher age, female gender, pain characteristics and psychological factors are associated with use Future studies should validate these fi...

Objectives Long-term opioid use after hip fracture surgery has been demonstrated in previously opioid-naïve elderly patients. It is unknown if the opioid type redeemed after hip surgery is associated with long-term opioid use. The aim of this study was to examine the association between the opioid type redeemed within the first three months after h...

Background Transdermal opioids are widely used among elderly adults with chronic pain. However, transdermal patches may be involved in a significant proportion of opioid-related patient safety incidents, as the application process includes several subprocesses, each associated with an individual risk of error. Objective The aim was to obtain specif...

Gastrointestinal (GI) pain — a form of visceral pain — is common in some disorders, such as irritable bowel syndrome, Crohn’s disease and pancreatitis. However, identifying the cause of GI pain frequently represents a diagnostic challenge as the clinical presentation is often blurred by concomitant autonomic and somatic symptoms. In addition, GI pa...

Many countries around the world have a very low per capita consumption of opioid analgesics, which is probably related to absence or inadequate management of moderate and severe pain for large parts of their populations. We conducted a longitudinal observational study with opioid analgesic consumption data for all countries from 2000–2015, to asses...

Background and aims Bariatric surgery remains a mainstay for treatment of morbid obesity. However, long-term adverse outcomes include chronic abdominal pain and persistent opioid use. The aim of this review was to assess the existing data on prevalence, possible mechanisms, risk factors, and outcomes regarding chronic abdominal pain and persistent...

Background/aims: Opioids cause gastrointestinal (GI) dysmotility, decrease gut secretion, and affect gut sphincters. Symptoms of opioid-induced bowel dysfunction may be alleviated by peripherally acting opioid antagonists like naloxegol, but detailed knowledge on GI effects of this drug is lacking. We hypothesized that naloxegol, compared to place...

[This corrects the article DOI: 10.1371/journal.pone.0171723.].

Oral controlled‐release formulations are playing an ever‐increasing role in opioid therapy; however, little is known about their influence on the relationship between pharmacokinetics and pharmacodynamics. The study aim was to characterise the pharmacokinetic‐pharmacodynamics of two controlled‐release tablet formulations and a liquid formulation of...

Background: Conditioned pain modulation (CPM) and offset analgesia are different features of descending pain inhibition. This study investigated CPM, offset analgesia and clinical pain measures in patients with knee osteoarthritis (KOA) before and after treatment with the combination of a non-steroidal anti-inflammatory drug (NSAIDs) plus acetamin...

Background: Abdominal pain is the most common symptom in chronic pancreatitis and has extensive impact on patients' lives. Quantitative sensory testing (QST) provides information on sensitivity to pain and mechanisms which can help quantify pain and guide treatment. The aims of this study were (1) to explore sensitivity to pain in patients with ch...

Polyneuropathy is a common complication to diabetes. Neuropathies within the enteric nervous system are associated with gastroenteropathy and marked symptoms that severely reduce quality of life. Symptoms are pleomorphic but include nausea, vomiting, dysphagia, dyspepsia, pain, bloating, diarrhoea, constipation and faecal incontinence. The aims of...

Background There is currently a knowledge gap regarding persistent opioid use after hip fracture surgery. Thus, opioid use within a year after hip fracture surgery in patients with/without opioid use before surgery was examined. Methods This population‐based cohort study included all patients (aged≥65) undergoing primary hip fracture surgery in De...

Introduction Pain is the most common symptom in chronic pancreatitis and treatment remains a challenge. Management of visceral pain in general, is only sparsely documented, and treatment in the clinic is typically based on empirical knowledge from somatic pain conditions. This may be problematic, as many aspects of the neurobiology differ significa...

Objective: Use of opioids for pain management has increased over the past decade; however, inadequate analgesic response is common. Genetic variability may be related to opioid efficacy, but due to the many possible combinations and variables, statistical computations may be difficult. This study investigated whether data processing with support v...

Opioid analgesics are the mainstay for treatment of moderate and severe pain but, in many countries, the consumption of these medicines is inadequate. Over time, various groups have published opioid analgesic metrics, including authors from the World Health Organization. They linked consumption to a level considered adequate based on the actual con...

Objectives Access to emergency drug kits (EDK) during medical emergencies can be life-saving; however, recent doubts about the quality of the kits have been expressed. Procurements of pharmaceuticals to the five regional authorities in Denmark are serviced by Amgros, a public sector organisation owned by the regions and established to create econom...

It is not straightforward to simultaneously evaluate the beneficial and harmful effects of pain management, since different drugs may possess different analgesia and adverse effect profiles. Utility functions, derived from the pharmacokinetics and pharmacodynamics of individual outcome parameters, have been constructed to address this problem. Here...

Joint inflammation is present in a subpopulation of knee osteoarthritic (KOA) patients. Pro-inflammatory cytokines are known to sensitize the peripheral and central pain pathways. This can be mechanistically assessed by pressure pain thresholds and temporal summation of pain (TSP). Non-steroidal anti-inflammatory drugs (NSAIDs) combined with parace...

Introduction: Correlations between subjective and objective measures of constipation have seldom been demonstrated. This could be due to multiple confounding factors in clinical studies and the broad span of symptoms represented in questionnaires used to assess constipation. We developed a new method for categorizing gastrointestinal (GI) symptoms...

Patients are often prescribed opioids after hospital discharge for surgery. However, several studies have shown that at least 3% of preoperative opioid-naive patients continue to use opioids for a long time after surgery. Prolonged opioid use is associated with serious side effects such as physical and psychological dependence, cognitive disturbanc...

Background and aims Offset analgesia (OA) is a pain modulating mechanism described as a disproportionately large decrease in pain intensity evoked by a minor decrease in stimulus intensity. Precise mechanisms of OA are still not elucidated and studies are needed to evaluate factors modulating OA. The aim of this study was to investigate OA before a...

Offset analgesia (OA) is a pain‐modulating mechanism described as a disproportionately large decrease in pain intensity evoked by a discrete decrease in stimulus temperature. The role of the opioidergic, serotonergic and noradrenergic systems on OA remains unclear. The aim of the present study was to evaluate whether OA is modulated by an opioid (o...

Pain involves responses in which both peripheral and central mechanisms contribute to the generation of pain. Pre‐clinical laboratory data have supported that a topical formulation of combined diclofenac and methadone (Diclometh) may alleviate local pain, and potentially the side effect profile should be low. We hypothesized that anti‐allodynic and...

Aim: Different mechanisms may be involved in the antinociceptive effects of oxycodone (opioid) and venlafaxine (serotonin-norepinephrine reuptake inhibitor), and the aim of this study was to investigate the effect of these drugs on brain functional connectivity. Methods: Resting state functional magnetic resonance imaging was acquired in 20 heal...

Background and aims: Opioid treatment interferes with anal sphincter function and its regulation during defecation. This may result in straining, incomplete evacuation, and contribute to opioid-induced bowel dysfunction (OIBD). Employing an experimental model of oxycodone-induced OIBD, we hypothesized that co-administration of the peripherally act...

Background: Factors such as age, gender and genetic polymorphisms may explain individual difference in pain phenotype. Genetic associations to pain sensitivity have previously been investigated in osteoarthritis patients with focus on the P2X7, TRPV1 and TACR1 genes. However, other genes may play a role as well. Osteoarthritis is a common joint di...

Background Non-Steroidal Anti-Inflammatory Drug (NSAID) treatment is recommended as the first step in the treatment of knee osteoarthritis (KOA). Due to the risk of side-effects of NSIADs and low responds rate, methods for selection of NSAID responders are highly warranted. Recent studies suggest that pain sensitization in KOA might be predictive f...

Aims Opioid treatment is associated with gastrointestinal (GI) side effects, known as opioid-induced bowel dysfunction (OIBD). Symptoms of OIBD are caused by opioid receptor activation in the enteric nervous system, which results in increased GI transit time and increased faecal volume in the colon. OIBD can be experimentally induced in healthy par...

Introduction: Opioids and antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) are recognized as analgesics to treat moderate to severe pain, but the central mechanisms underlying their analgesia remain unclear. This study investigated how brain activity at rest and exposed to tonic pain is modified by oxycodone (opioid) and v...

Opioids are increasingly used for treatment of chronic pain. However, they are only effective in a subset of patients and have multiple side effects. Thus, studies using biomarkers for response are highly warranted. The current study prospectively examined 63 opioid-naïve patients initiating opioid use for diverse types of chronic pain at five Euro...

STROBE Statement—Checklist of items that should be included in reports of cohort studies. (PDF)

Opioids are potent analgesics. Opioids exert effects after interaction with opioid receptors. Opioid receptors are present in the peripheral- and central nervous system (CNS), but the analgesic effects are primarily mediated via receptors in the CNS. Objective methods for assessment of opioid effects may increase knowledge on the CNS processes resp...

Background: Gastrointestinal symptoms are common in the general population and may originate from disturbances in gut motility. However, fundamental mechanistic understanding of motility remains inadequate, especially of the less accessible regions of the small bowel and colon. Hence, refinement and validation of objective methods to evaluate moti...

Human studies on experimentally induced pain are of value to elucidate the genetic influence on morphine analgesia under controlled conditions. The aim of this study was to investigate if genetic variants of mu, kappa and delta opioid receptor genes (OPRM1, OPRK1 and OPRD1) and catechol-O-methyltransferase gene (COMT) are associated with the morphi...

Aim: A high inter-individual variation in the pharmacokinetics and pharmacodynamics of morphine has been observed. Genetic polymorphisms in genes encoding the organic cation transporter isoform 1 (OCT1), the efflux transporter p-glycoprotein (ABCB1), and the UDP-glucuronosyltransferase-2B7 (UGT2B7) may influence morphine pharmacokinetics and thus,...

Severe pain is often treated with opioids. Antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) have also shown a pain relieving effect, but for both SNRI and opioids the specific mode of action in humans remains vague. This study investigated how oxycodone and venlafaxine affect spinal and supraspinal pain processing. Twenty v...

Background: Standardized objective methods to assess the analgesic effects of opioids, enable identification of underlying mechanisms of drug actions in the central nervous system. Opioids may exert their effect on both cortical and spinal levels. In this study actions of morphine at both levels were investigated, followed by analysis of a possibl...

Aims To employ a human experimental model of opioid-induced bowel dysfunction (OIBD) in healthy volunteers, and evaluate the impact of opioid treatment compared to placebo on gastrointestinal (GI) symptoms and motility, assessed by questionnaires and regional GI transit times. Methods Twenty-five healthy males were randomly assigned to oxycodone o...

Despite marked differences in underlying pathophysiology, the current management of visceral pain largely follows the guidelines derived from the somatic pain literature. The effective management of patients with chronic visceral pain should be multifaceted, including both pharmacological and psychological interventions, thereby providing a mechani...

Joint analysis of pain intensity and opioid consumption is encouraged in trials of postoperative pain. However, previous approaches have not appropriately addressed the complexity of their interrelation in time. In this study, we applied a non-linear mixed effects model to simultaneously study pain intensity and opioid consumption in a 4-h postoper...

The genetic influence on sensitivity to noxious stimuli (pain sensitivity) remains controversial and needs further investigation. In the present study, the possible influence of polymorphisms in three opioid receptor (OPRM, OPRD and OPRK) genes, and the catechol-O-methyltransferase (COMT) gene on pain sensitivity in healthy participants were invest...

Background and purpose: Magnetic resonance spectroscopy (MRS) is used to measure brain metabolites. Limited data exist on the analgesic-induced spectroscopy response. This was an explorative study with the aims to investigate the central effects of two analgesic drugs, an opioid and a selective serotonin and norepinephrine reuptake inhibitor, and...

Background: Polymorphisms in the opioid receptor genes may affect the pharmacodynamics (PD) of oxycodone and be part of the reason behind the diversity in clinical response. The aim of the analysis was to model the exposure-response profile of oxycodone for three different pain variables and search for genetic covariates. Model simulations were us...

Background: Gastro-oesophageal reflux disease (GORD) is a major health problem that is frequently accompanied by debilitating oesophageal pain symptoms. Objectives: The first objective of the study was to examine the association between catastrophizing and oesophageal pain sensitivity. The second objective was to examine whether catastrophizing...

Characterization of gut pain is fundamental in the diagnosis and assessment of organ dysfunction, leading to optimal treatment. Quantitative sensory testing (QST) provides information on sensory function at the peripheral and central level of the nervous system by recording subjects’ responses (subjective or objective) to different external stimuli...

Background: The analgesic effect of opioids is often based on subjective one dimensional measurements. Electroencephalography (EEG) offers a possibility to objectively quantify the brain's activity before and after the administration of opioids. The aim of this study was to investigate the pharmacokinetic-pharmacodynamic (PKPD) properties of the b...

Current findings on altered evoked potentials (EPs) caused by morphine are based on common alterations for a group of subjects after drug administration. However, this ignores the analysis of individual responses, which may explain the clinical differences in efficacy. Therefore, we explored the individual responses to morphine in terms of the alte...

In recent years prescription of opioids has increased significantly. Although effective in pain management, bothersome gastrointestinal adverse effects are experienced by a substantial proportion of opioid-treated patients. This can lead to difficulties with therapy and subsequently inadequate pain relief. Collectively referred to as opioid-induced...

Opioids are used for the treatment of pain. However, 30-50% of patients have insufficient effect to the opioid initially selected by the physician, and there is an urgent need for biomarkers to select responders to the most appropriate drug. Since opioids mediate their effect in the central nervous system, this study aimed to investigate if electro...

Human experimental pain studies are of value to study basic pain mechanisms under controlled conditions. The aim of this study was to investigate if genetic variation across selected mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1and OPRD1 respectively) influenced analgesic response to oxycodone in healthy volunteers. Experimental multi-m...

Knowledge about cerebral mechanisms underlying pain perception and effect of analgesic drugs is important for developing methods for diagnosis and treatment of pain. The aim was to explore altered brain activation before and after morphine treatment using functional magnetic resonance imaging recorded during experimental painful heat stimulation. F...

Morphine is a widely used opioid for treatment of moderate to severe pain, but large interindividual variability in patient response and no clear guidance on how to optimise morphine dosage regimen complicates treatment strategy for clinicians. Population pharmacokinetic-pharmacodynamic models can be used to quantify dose-response relationships for...

Chronic pancreatitis (CP) is an inflammatory disease that causes irreversible damage to pancreatic tissue. Pain is its most prominent symptom. In the absence of pathology suitable for endoscopic or surgical interventions, pain treatment usually includes opioids. However, opioids often have limited efficacy. Moreover, side effects are common and bot...

Background Opioid antagonists are increasingly used to abolish the gastrointestinal side effects of opioids. However, they can potentially interfere with local analgesia exerted via opioid receptors in the gut. Thus, in the current study we aimed to explore the effect of rectal morphine before and after blocking opioid receptors outside the central...

Introduction: In experimental pain research the effect of opioids is normally assessed by verbal subjective response to analgesia. However, as many confounders in pain assessment exist, objective bed-side assessment of the effect is highly warranted. Therefore, we aimed to assess the effect of morphine on three objective pharmacodynamic markers (p...

Opioid analgesia can be explored with quantitative sensory testing, but most investigations have used models of phasic pain, and such brief stimuli may be limited in the ability to faithfully simulate natural and clinical painful experiences. Therefore, identification of appropriate experimental pain models is critical for our understanding of opio...

Objective: Gastroesophageal reflux disease (GERD) is a common condition associated with symptoms as heart burn, regurgitation, chest pain, and gastrointestinal discomfort. PPC-5650 is a new pharmacological agent that can modulate acid-sensing ion channel activity, potentially leading to reduction in the pain signal. In healthy volunteers the esoph...