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Sigma-1 receptor (σ1R) ligands have been shown to be effective at relieving neuropathic and inflammatory pain, but have not yet been tested in experimental models of fibromyalgia. The objective of this study was to evaluate the effect of a σ1R antagonist (BD1063) compared to pregabalin. ICR-CD1 female mice were subjected to either six repeated injections of reserpine, to cause reserpine-induced myalgia (RIM6), or acidified saline intramuscular injections (ASI). In these two models, we evaluated the effect of BD1063 and pregabalin on thermal hypersensitivity, anxiety-like and depression-like behaviors, and on spinal cord gliosis. BD1063 exerted an antinociceptive effect on both reflexive (thermal hyperalgesia) and nonreflexive (anxiety- and depression-like) pain behaviors, and reduced spinal astroglial and microglial reactivity, following repeated treatment for 2 weeks. Interestingly, the effects of BD1063 were long-term, lasting several weeks after treatment discontinuation in both fibromyalgia-like models. Similar results were obtained with pregabalin, but the effects on pain behaviors lasted for a shorter length of time, and pregabalin did not significantly modulate spinal glial reactivity. The inhibitory and long-lasting effect of pharmacological blockade of σ1Rs on both sensory and affective dimensions of nociplastic-like pain and spinal cord gliosis in two experimental models of fibromyalgia support the application of this therapeutic strategy to treat fibromyalgia.
Learn More >To assess studies examining the prevalence of chronic pain (CP) in patients treated with Opioid Substitution Treatment (OST – buprenorphine or methadone) for Opioid Used Disorder (OUD), we conducted a systematic review and meta-analysis of the literature between the years 2000 and 2020. We searched EMBASE, PsycINFO, Cochrane, and MEDLINE databases and included studies assessing the prevalence of CP in OUD adults treated with OST. The studies were assessed for risk of bias and overall quality and the results were pooled using a random-effects model. Subgroup analyses and meta-regressions were used to identify possible factors associated with CP. Twenty-three studies reported data on the prevalence of CP in patients treated with OST were evaluated. The prevalence obtained was 45.3% (CI95% [38.7; 52.1]). Overall, 78.3% of the studies had a low risk of bias. Subgroup analysis estimates did not vary according to gender, OST, and CP duration. However, it appeared that the clinical settings was associated with a lower CP prevalence when assessed in primary care sites. Our study provided an estimate regarding the prevalence of CP among OST patients. These patients deserve specific attention from health professionals and health authorities. Thus, the real challenge in OST patients is the implementation of a multidisciplinary approach to manage CP. REGISTRATION: PROSPERO (CRD42021284790) PERSPECTIVE: Our meta-analysis provided an estimate of CP prevalence, reaching almost 50% of OUD patients with OST. Thus, the urgent challenge in OST patients is to pay systematic attention to chronic pain diagnosis, along with the implementation of a multidisciplinary patient-focused approach for an appropriate management of CP.
Learn More >The 0 to 10 numeric rating scale (NRS) of pain intensity is a standard outcome in randomized controlled trials (RCTs) of pain treatments. For individuals taking analgesics, there may be a disparity between "observed" pain intensity (pain intensity with concurrent analgesic use) and pain intensity without concurrent analgesic use (what the NRS would be had concurrent analgesics not been taken). Using a contemporary causal inference framework, we compare analytic methods that can potentially account for concurrent analgesic use, first in statistical simulations, and second in analyses of real (non-simulated) data from an RCT of lumbar epidural steroid injections (LESI). The default analytic method was ignoring analgesic use, which is the most common approach in pain RCTs. Compared to ignoring analgesic use and other analytic methods, simulations showed that a quantitative pain and analgesia composite outcome based on adding 1.5 points to pain intensity for those who were taking an analgesic (the QPAC) optimized power and minimized bias. Analyses of real RCT data supported the results of the simulations, showing greater power with analysis of the QPAC as compared to ignoring analgesic use and most other methods examined. We propose alternative methods that should be considered in the analysis of pain RCTs. PERSPECTIVE: This article presents the conceptual framework behind a new quantitative pain and analgesia composite outcome, the QPAC, and the results of statistical simulations and analyses of trial data supporting improvements in power and bias using the QPAC. Methods of this type should be considered in the analysis of pain RCTs.
Learn More >The objective of this study was to determine the effect of enhancing conventional care for people with chronic painful temporomandibular disorders (TMD) with an individualised contemporary pain science education (PSE) intervention. In this randomized controlled trial, a consecutive sample of 148 participants (18 to 55 years of age) was randomized into two groups: PSE-enhanced conventional care or Conventional care alone. Conventional care involved a six-week, 12-session manual therapy and exercise program. The PSE enhancement involved two sessions of modern PSE, undertaken in the first two treatment sessions. Primary outcomes were pain intensity, assessed with a numeric pain rating scale, and disability, assessed with the craniofacial pain and disability inventory, post-treatment. Linear mixed model analyses were used to investigate between-group differences over time. There was a statistically and clinically meaningful effect of PSE enhancement on disability (Mean Difference = 6.1, 95% CI: 3.3 to 8.8), but not on pain intensity, post-treatment. Secondary analyses suggested clinically meaningful benefit of PSE enhancement on pain and disability ratings at 10-week and 18-week follow-ups, raising the possibility that preceding conventional care with a PSE intervention may result in long-term benefits. Perspective: The addition of modern Pain Science Education (PSE) intervention improved disability for people with chronic TMD receiving manual therapy and exercise, but not pain. A mean difference in pain and disability favoring the PSE group at the 10- and 18-week follow-ups, respectively, suggests that PSE addition resulted in longer-lasting effects. Trial registration: NCT03926767. Registered on April 29, 2019. https://clinicaltrials.gov/ct2/show/NCT03926767.
Learn More >Diabetic neuropathy (DN) remains arguably the most prevalent chronic complication in people with both type 1 and type 2 diabetes, including in youth, despite changes in the current standards of clinical care. Additionally, emerging evidence demonstrates that neuropathy affects a large proportion of people with undiagnosed diabetes and/or prediabetes, as well as those with obesity. Here we summarize the latest epidemiology of DN, recent findings regarding the pathophysiology of the disease, as well as current outcome measures for screening and diagnosis, in research and clinical settings. The authors discuss novel perspectives on the impact of social determinants of health in DN development and management, and the latest evidence on effective therapies, including pharmacological and nonpharmacological therapies for neuropathic pain. Throughout the publication, we identify knowledge gaps and the need for future funding to address these gaps, as well as needs to advocate for a personalized care approach to reduce the burden of DN and optimize quality of life for all affected individuals.
Learn More >Children who undergo wound manipulation usually experience pain. Virtual reality technology is a novel and effective non pharmaceutical therapy for reducing pain in children scheduled to undergo wound manipulation. However, the effectiveness of Virtual reality technology in controlling procedural pain in children's wounds has not been evaluated in a systematic review.
Learn More >Chronic pain is a common experience in osteogenesis imperfecta (OI). However, there are few studies on this topic, and none of them emerge from psychology as a discipline. The purpose of this work is to describe the frequency of chronic pain and its characteristics in a large sample of adults with OI, as well as its relationship with clinical, sociodemographic, psychological, and quality of life variables. A cross-sectional study was carried out in a sample of 418 adults with OI who answered a battery of online questionnaires. Sociodemographic and clinical variables, pain parameters, participants' appraisal of pain, coping strategies, interference in daily activities, and health-related quality of life were evaluated. A descriptive and correlational analysis was performed. Up to 83% of the sample reported experiencing pain frequently. Both the frequency and intensity of pain were related to the accumulation of fractures over the years (P < .05), but were independent of other variables like the severity of the pathology or the use of bisphosphonates. Higher threat appraisal of pain was associated with an increase in perceived pain intensity and its interference with daily activities, as well as a decrease in physical and mental health (P < .001). Chronic pain frequent condition in adults with OI, regardless of the severity of the pathology. It interferes with their usual activities and has an impact on their quality of life. The way in which participants appraise their pain also have an influence on its intensity and its consequences. Interventions aimed at training strategies for managing appraisals about pain could potentially improve adaptation to chronic pain.
Learn More >Chronic pain (CP) is a major public health issue. While new onset CP is known to occur frequently after some pediatric surgeries, its incidence after the most common pediatric surgeries is unknown. This retrospective cohort study used insurance claims data from 2002 to 2017 for patients 0-21 years of age. The primary outcome was CP 90-365 days after each of the 20 most frequent surgeries in five age categories (identified using CP ICD codes). Multivariable logistic regression identified surgeries and risk factors associated with CP after surgery. A total of 424,590 surgical patients aged 0-21 were included, 22,361 of whom developed CP in the 90-365 days after surgery. The incidences of CP after surgery were: 1.1% in age group 0-1 years; 3.0% in 2-5 years; 5.6% in 6-11 years; 10.1% in 12-18 years; 9.9% in 19-21 years. Some surgeries and patient variables were associated with CP. Approximately one in ten adolescents who underwent the most common surgeries developed CP, as did a striking percentage of children in other age groups. Given the long-term consequences of CP, resources should be allocated toward identification of high-risk pediatric patients and strategies to prevent CP after surgery.
Learn More >In neuropathic pain clinical trials, the patient's perspective is often insufficiently reflected focusing mainly on pain intensity. Comparability of outcome assessment is limited due to heterogenous patient-reported outcome measures (PROMs). The MEDLINE, CENTRAL, and Embase databases and reference lists of published meta-analyses were searched. Randomized controlled studies assessing treatment efficacy of drugs for chronic neuropathic pain were included. PROMs were assigned to recommended IMMPACT/NeuPSIG domains: pain intensity, pain other aspects, physical functioning, emotional functioning, global improvement and satisfaction, adverse events, participant disposition. Domains and PROMs were compared regarding the publication year and methodological quality of the studies. Within the 251 included studies 200 PROMs were used with 27 being recommended by IMMPACT/NeuPSIG. The number of domains was higher in high/moderate quality studies. The (sub-) domains 'physical functioning', 'global improvement and satisfaction', and 'neuropathic pain quality' were assessed more frequently in high/moderate quality studies and those published after 2011. Recent studies and those of better quality more often used the recommended PROMs. Although neuropathic assessment via PROMs has improved, there is still a high heterogeneity. A standardized core set of outcome domains and should be defined to improve neuropathic pain treatment and to achieve better comparability of clinical trials. Perspective: This systematic literature review assesses the use of patient reported outcome measures (PROMs) in chronic neuropathic pain. The results show that there is still a high heterogeneity, highlighting the need for a standardized core set of outcome domains and PROMs to improve comparability of clinical trials and neuropathic pain treatment.
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