Evidence Of Analgesic Efficacy Research Articles

P098 Changes in Analgesic Prescribing in Patients with Inflammatory Arthritis in England: An Observational Study in CPRD Aurum

Abstract Background/Aims Pain is a common symptom experienced by patients with inflammatory arthritis (IA). Emerging data indicate IA pain treatment focuses on prescribing analgesics despite an absence of evidence for long-term efficacy. Delivering optimal, equitable IA pain care in England requires understanding current practice. To address this, we evaluated analgesic prescribing in patients diagnosed with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (SpA) contributing data to the Clinical Practice Research Datalink Aurum, a primary care electronic health record database covering 20% of England. Methods Cross-sectional analyses (2004-2020) evaluated the annual prevalence of analgesic prescriptions in patients with RA/PsA/axial SpA. These were reported stratified by age, gender, ethnicity, deprivation, and geographical region. Analgesic prescriptions were classified using Bedson et al’s hierarchical system with an additional gabapentinoid group. Joinpoint regression models evaluated time-points when a significant change in the trends of prescription annual prevalence occurred. Results Although declining over time, the annual prevalence of analgesic prescriptions remained high (84.2% [95% CI 83.9, 84.5] in 2004; 64.5% [95% CI 64.2, 64.8] in 2020). In 2004, oral NSAIDs were the commonest analgesic (prevalence 56.1% [95% CI 55.8, 56.5]). By 2020, this fell to 22.3% (95% CI 22.1, 22.6) with opioids being the commonest analgesic (prevalence 39.0% [95% CI 38.7, 39.2]). Most opioid prescriptions were “strong/very strong” and long-term. Annual prevalence of non-NSAID analgesic prescriptions was highest in RA and of NSAIDs was highest in axial SpA. The annual prevalence of all analgesic types except NSAIDs differed by age, sex, deprivation, ethnicity, and region. Annual prevalence of non-NSAID analgesic prescriptions increased with age and deprivation, were higher in females than males, and higher in Northern than Southern England. The opposite pattern was seen with age for oral NSAIDs. NSAIDs were more commonly prescribed in males than females. Very little difference was seen in NSAID prescribing by deprivation, ethnicity, and region. There was a significant change in the trend of opioid prescription annual prevalence in 2015 (year of Public Health England’s “Opioid Aware” release) when the rate of decline increased, and at 2013 and 2018 for gabapentinoids when the annual prevalence increase slowed then declined (years of NHS England’s release of information on gabapentinoid risks, and their reclassification as controlled substances). Conclusion Whilst overall national analgesic prescribing in IA has fallen over 17 years - with interventions to deliver safer opioid/gabapentinoid prescribing potentially contributing - it remains common. This is at variance with evidence of analgesic efficacy and risks. The differences in prescribing of some analgesic types by patient sociodemographic factors and regions suggest unwarranted variation. Interventions are needed to improve the delivery of effective, equitable IA pain treatment. Disclosure I.C. Scott: None. R. Whittle: None. J. Bailey: None. H. Twohig: None. S.L. Hider: None. C.D. Mallen: None. S. Muller: None. K.P. Jordan: None.

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

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

Developing Improved Translational Models of Pain: A Role for the Behavioral Scientist.

The effective management of pain is a longstanding public health concern. Although opioids have been frontline analgesics for decades, they also have well-known undesirable effects that limit their clinical utility, such as abuse liability and respiratory depression. The failure to develop better analgesics has, in some ways, contributed to the escalating opioid epidemic that has claimed tens of thousands of lives and has cost hundreds of billions of dollars in health-care expenses. A paradigm shift is needed in the pharmacotherapy of pain management that will require extensive efforts throughout biomedical science. The purpose of the present review is to highlight the critical role of the behavioral scientist to devise improved translational models of pain for drug development. Despite high heterogeneity of painful conditions that involve cortical-dependent pain processing, current models often feature an overreliance on simple reflex-based measures and an emphasis on the absence, rather than presence, of behavior as evidence of analgesic efficacy. Novel approaches should focus on the restoration of operant and other CNS-mediated behavior under painful conditions.

Corticosteroids for Pain of Spinal Origin: Epidural and Intraarticular Administration.

Targeted interventional delivery of corticosteroids remains a mainstay of treatment for spinal pain syndromes because this approach has a wider therapeutic index than other approaches. The best evidence for analgesic efficacy is in subacute radicular syndromes associated with new-onset or recurrent lumbar radiculitis. Complications often relate to drug delivery technique as much as actions of the steroid itself and require careful consideration and vigilance by the administering physician. Considerable uncertainty persists concerning which patients with chronic pain are most likely to benefit from corticosteroid injections. Matching this treatment option with specific spinal pain syndromes remains a major challenge.

Evaluation of the analgesic efficacy and psychoactive effects of AZD1940, a novel peripherally acting cannabinoid agonist, in human capsaicin‐induced pain and hyperalgesia

The aim of the present study was to investigate the effects of AZD1940, a novel peripherally acting cannabinoid CB(1) /CB(2) receptor agonist, on capsaicin-induced pain and hyperalgesia, as well as on biomarkers of cannabinoid central nervous system (CNS) effects. The present study was a randomized, double-blind, placebo-controlled, four-sequence, two-period, cross-over study in 44 male healthy volunteers aged 20-45 years. The effects of two single oral doses of AZD1940 (400 and 800 μg) were compared with placebo. Pain intensity after intradermal capsaicin injections in the forearm was assessed on a continuous visual analogue scale (VAS; 0-100 mm). Primary and secondary hyperalgesia induced by application of capsaicin cream on the calf were assessed by measuring heat pain thresholds and the area of mechanical allodynia, respectively. The CNS effects were assessed at baseline and up to 24 h after dosing using a visual analogue mood scales (VAMS) for feeling 'stimulated', 'high', 'anxious', 'sedated' or 'down'. AZD1940 did not significantly attenuate ongoing pain or primary or secondary hyperalgesia compared with placebo. Mild CNS effects for AZD1940were observed on the VAMS for 'high' and 'sedated'. Dose-dependent mild-to-moderate CNS-related and gastrointestinal adverse events were reported following treatment with AZD1940. No evidence of analgesic efficacy was found for a peripherally acting CB(1)/CB(2) receptor agonist in the human capsaicin pain model. The emergence of mild dose-dependent CNS effects suggests that the dose range predicted from preclinical data had been attained.

An examination of the analgesic effects of microcurrent electrical stimulation (MES) on cold-induced pain in healthy subjects

Microcurrent electrical stimulation (MES) is an electrotherapeutic approach proposed by manufacturers for the management of acute and chronic pain. Evidence for analgesic efficacy is anecdotal and few controlled studies have been performed to date. This single-blind, placebo-controlled study examined the analgesic effects of MES on experimentally induced pain threshold and pain intensity rating in 36 healthy non-paid university student volunteers. Pain threshold and pain intensity recordings to cold-induced pain were made before, during and after a 20 min treatment session. Subjects received either active MES (DC biphasic pulses, 600 μA, 103 pulses per second) or placebo MES (no current output). The results showed no significant differences between active MES and placebo MES for the change in ice pain threshold or pain intensity rating during treatment. However, a significant increase in pain threshold was found in both active MES and placebo MES during the treatment cycles when compared to pre-treatment baseline. This change in pain threshold during active and placebo MES was similar in magnitude to placebo transcutaneous electrical nerve stimulation (TENS) and lower than active TENS as previously reported by ourselves. We conclude that the analgesic effects of active MES on cold-induced pain in healthy subjects were no greater than placebo. It is important to extend these laboratory findings by investigating the clinical efficacy of MES in patients with pain.