Range Of Pain Conditions Research Articles

NIH HEAL Initiative: National Institute of Neurological Disorders and Stroke Preclinical Program for Non-Addictive Pain Therapeutic Development

Background: The NIH Helping to End Addiction Long-term (HEAL) Initiative aims to focus efforts on advancing scientific solutions to stem the opioid crisis, improving prevention and treatment of opioid misuse/addiction, and enhancing pain management. Goal: NINDS is charged with accelerating the discovery and development of new non-addictive pharmacologic and non-pharmacologic pain therapeutics as part of the HEAL Initiative. NINDS established the Preclinical Screening Platform for Pain (PSPP) to accelerate and enhance testing of novel, non-addictive pain therapeutics. This program will evaluate new, as well as repurposed, small molecules, biologics, devices, and natural products across a range of pain conditions. PSPP is accepting assets from academic and industry sponsors, worldwide. Here we describe efforts within the PSPP program. The overall goal of the PSPP program is to provide an efficient, rigorous, one-stop in vivo screening resource to accelerate identification and efficacy profiling of non-opioid therapeutics for the treatment of pain. Under NINDS direction, preclinical testing of submitted agents is performed by contract facilities on a blinded and confidential basis at no cost to the PSPP participants. Test candidates are evaluated in a suite of in vivo pain-related endpoints and models, following in vitro receptor profiling, pharmacokinetic and safety assessment. Importantly, test candidates are also evaluated in models of abuse liability. We will describe the advances made to date towards establishing program goals of evaluating assets in a rigorous and reproducible manner. Background: The NIH Helping to End Addiction Long-term (HEAL) Initiative aims to focus efforts on advancing scientific solutions to stem the opioid crisis, improving prevention and treatment of opioid misuse/addiction, and enhancing pain management. Goal: NINDS is charged with accelerating the discovery and development of new non-addictive pharmacologic and non-pharmacologic pain therapeutics as part of the HEAL Initiative. NINDS established the Preclinical Screening Platform for Pain (PSPP) to accelerate and enhance testing of novel, non-addictive pain therapeutics. This program will evaluate new, as well as repurposed, small molecules, biologics, devices, and natural products across a range of pain conditions. PSPP is accepting assets from academic and industry sponsors, worldwide. Here we describe efforts within the PSPP program. The overall goal of the PSPP program is to provide an efficient, rigorous, one-stop in vivo screening resource to accelerate identification and efficacy profiling of non-opioid therapeutics for the treatment of pain. Under NINDS direction, preclinical testing of submitted agents is performed by contract facilities on a blinded and confidential basis at no cost to the PSPP participants. Test candidates are evaluated in a suite of in vivo pain-related endpoints and models, following in vitro receptor profiling, pharmacokinetic and safety assessment. Importantly, test candidates are also evaluated in models of abuse liability. We will describe the advances made to date towards establishing program goals of evaluating assets in a rigorous and reproducible manner.

Peritraumatic Plasma Omega-3 Fatty Acid Concentration Predicts Chronic Pain Severity Following Thermal Burn Injury.

Chronic pain is a significant comorbidity of burn injury affecting up to 60% of survivors. Currently, no treatments are available to prevent chronic pain after burn injury. Accumulating evidence suggests that omega-3 fatty acids (O3FAs) improve symptoms across a range of painful conditions. In this study, we evaluated whether low peritraumatic levels of O3FA predict greater pain severity during the year after burn injury. Burn survivors undergoing skin autograft were recruited from three participating burn centers. Plasma O3FA (n = 77) levels were assessed in the early aftermath of burn injury using liquid chromatography/mass spectrometry, and pain severity was assessed via the 0 to 10 numeric rating scale for 1 year following burn injury. Repeated-measures linear regression analyses were used to evaluate the association between peritraumatic O3FA concentrations and pain severity during the year following burn injury. Peritraumatic O3FA concentration and chronic pain severity were inversely related; lower levels of peritraumatic O3FAs predicted worse pain outcomes (β = -0.002, P = .020). Future studies are needed to evaluate biological mechanisms mediating this association and to assess the ability of O3FAs to prevent chronic pain following burn injury.

The efficacy and safety of paracetamol for pain relief: an overview of systematic reviews.

To evaluate the efficacy and safety of paracetamol as an analgesic medication in a range of painful conditions. Systematic review of systematic reviews of the analgesic effects of paracetamol in randomised, placebo-controlled trials. Conduct of systematic reviews was assessed with AMSTAR-2; confidence in effect estimates (quality of evidence) was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. MEDLINE, EMBASE, PsycINFO, Cochrane Database of Systematic Reviews; systematic reviews published 1 January 2010 - 30 April 2020. We extracted pain and adverse events outcomes from 36 systematic reviews that assessed the efficacy of paracetamol in 44 painful conditions. Continuous pain outcomes were expressed as mean differences (MDs; standardised 0-10-point scale); dichotomous outcomes were expressed as risk ratios (RRs). There is high quality evidence that paracetamol provides modest pain relief for people with knee or hip osteoarthritis (MD, -0.3 points; 95% CI, -0.6 to -0.1 points) and after craniotomy (MD, -0.8 points; 95% CI, -1.4 to -0.2 points); there is moderate quality evidence for its efficacy in tension-type headache (pain-free at 2 hours: RR, 1.3; 95% CI, 1.1-1.4) and perineal pain soon after childbirth (patients experiencing 50% pain relief: RR, 2.4; 95% CI, 1.5-3.8). There is high quality evidence that paracetamol is not effective for relieving acute low back pain (MD, 0.2 points; 95% CI, -0.1 to 0.4 points). Evidence regarding efficacy in other conditions was of low or very low quality. Frequency of adverse events was generally similar for people receiving placebo or paracetamol, except that transient elevation of blood liver enzyme levels was more frequent during repeated administration of paracetamol to patients with spinal pain (RR, 3.8; 95% CI, 1.9-7.4). For most conditions, evidence regarding the effectiveness of paracetamol is insufficient for drawing firm conclusions. Evidence for its efficacy in four conditions was moderate to strong, and there is strong evidence that paracetamol is not effective for reducing acute low back pain. Investigations that evaluate more typical dosing regimens are required. CRD42015029282 (prospective).

Evidence-Based Psychological Interventions for the Management of Pediatric Chronic Pain: New Directions in Research and Clinical Practice.

Over the past 20 years our knowledge about evidence-based psychological interventions for pediatric chronic pain has dramatically increased. Overall, the evidence in support of psychological interventions for pediatric chronic pain is strong, demonstrating positive psychological and behavioral effects for a variety of children with a range of pain conditions. However, wide scale access to effective psychologically-based pain management treatments remains a challenge for many children who suffer with pain. Increasing access to care and reducing persistent biomedical biases that inhibit attainment of psychological services are a central focus of current pain treatment interventions. Additionally, as the number of evidence-based treatments increase, tailoring treatments to a child or family’s particular needs is increasingly possible. This article will (1) discuss the theoretical frameworks as well as the specific psychological skills and strategies that currently hold promise as effective agents of change; (2) review and summarize trends in the development of well-researched outpatient interventions over the past ten years; and (3) discuss future directions for intervention research on pediatric chronic pain.

(515) A cross-sectional survey of pain-related experiences and knowledge in emerging adults

Chronic pain is a common phenomenon in the U.S., known to occur across the lifespan (Institute of Medicine, 2011). Much remains to be learned, however, about the distribution of pain conditions in emerging adults or the knowledge that they have about pain. Greater knowledge about pain and its management can be effective for improving pain outcomes, even among at-risk individuals (Thorn et al., 2011). To improve this knowledge, we surveyed 200 emerging adults at a large public university in the geographic south about their chronic pain conditions (if present) and knowledge about pain and its management. Participants completed surveys online in exchange for course credit. Measures included a new computer-administered pain interview and two new pain measures, the Pain Knowledge Questionnaire (PKQ) and the Pain Skills Questionnaire (PSQ). The PKQ is a 23-item measure that investigates how much a person knows about the causes and treatments for chronic pain conditions, and the PSQ is a 10-item measure that assesses how often a person uses a variety of skills to manage pain when they experience it. Demographic results indicate that the sample approximated the general student population. The average participant was a white underclasswoman. A range of pain conditions were reported. Analyses indicate that participants demonstrate basic pain knowledge, but are often lacking in important facts associated with better pain outcomes. This knowledge also varies based on participant characteristics, such as the presence or absence of a pain condition. This study provides valuable information about the distribution of chronic pain conditions in a group of emerging adults and their knowledge about pain and pain management. It provides evidence for the lack of core pain information existing in the general student population, even among individuals with chronic pain conditions, and supports the need for greater pain education. Chronic pain is a common phenomenon in the U.S., known to occur across the lifespan (Institute of Medicine, 2011). Much remains to be learned, however, about the distribution of pain conditions in emerging adults or the knowledge that they have about pain. Greater knowledge about pain and its management can be effective for improving pain outcomes, even among at-risk individuals (Thorn et al., 2011). To improve this knowledge, we surveyed 200 emerging adults at a large public university in the geographic south about their chronic pain conditions (if present) and knowledge about pain and its management. Participants completed surveys online in exchange for course credit. Measures included a new computer-administered pain interview and two new pain measures, the Pain Knowledge Questionnaire (PKQ) and the Pain Skills Questionnaire (PSQ). The PKQ is a 23-item measure that investigates how much a person knows about the causes and treatments for chronic pain conditions, and the PSQ is a 10-item measure that assesses how often a person uses a variety of skills to manage pain when they experience it. Demographic results indicate that the sample approximated the general student population. The average participant was a white underclasswoman. A range of pain conditions were reported. Analyses indicate that participants demonstrate basic pain knowledge, but are often lacking in important facts associated with better pain outcomes. This knowledge also varies based on participant characteristics, such as the presence or absence of a pain condition. This study provides valuable information about the distribution of chronic pain conditions in a group of emerging adults and their knowledge about pain and pain management. It provides evidence for the lack of core pain information existing in the general student population, even among individuals with chronic pain conditions, and supports the need for greater pain education.

Tapentadol Immediate Release Versus Oxycodone Immediate Release for Treatment of Acute Low Back Pain

Background: Tapentadol has demonstrated analgesic efficacy across a range of pain conditions. Objective: In a head-to-head study of up to 10 days in duration, the analgesic efficacy and tolerability of tapentadol immediate release (IR) versus oxycodone IR using a flexible dosing regimen were compared in patients with acute low back pain (LBP) and associated radicular leg pain. Study Design: Randomized (1:1), double-blind, parallel-group study (NCT00986180). Independent Ethics Committee/Institutional Review Board approval of the protocol was obtained. Setting: Ninety US outpatient treatment centers. Methods: Patients with moderate to severe, acute LBP received tapentadol IR (50, 75, or 100 mg) or oxycodone HCl IR (5, 10, or 15 mg) every 4 to 6 hours as needed for pain for up to 10 days. Patients reported current pain intensity twice daily (11-point numerical rating scale). The primary efficacy endpoint was the sum of pain intensity differences (SPID) over 120 hours for LBP. Tapentadol IR was considered non-inferior to oxycodone IR if the upper bound of the 95% confidence interval (CI) for the least-squares mean (LSM) difference in SPID120 was less than 120. Secondary efficacy endpoints included 2-, 3-, and 10-day SPID for LBP; 2-, 3-, 5-, and 10-day SPID for index leg pain; 30% and 50% responder rates; patient and clinician global impressions of change; and patient satisfaction. Results: The safety population included 645 patients, and the modified intent-to-treat population included 585 patients. In the tapentadol IR and oxycodone IR groups, respectively, 86.3% (277/321) and 82.7% (268/324) of patients completed the study. The most common reason for study withdrawal in both treatment groups was adverse events (tapentadol IR, 6.5% [21/321]; oxycodone IR, 7.1% [23/324]). The LSM (standard error) SPID120 for LBP was 264.6 (11.43) for tapentadol IR (n = 287) and 264.0 (11.22) for oxycodone IR (n = 298). The 95% CI for the LSM difference was −32.1 to 30.9; therefore, tapentadol IR was non-inferior to oxycodone IR for relief of LBP. No significant differences were observed between tapentadol IR and oxycodone IR for other SPID endpoints or for responder rates. At the end of the study, in the tapentadol IR and oxycodone IR treatment groups, respectively, approximately two-thirds of patients (66.2% vs 66.2%) and clinicians (67.9% vs 66.6%) rated patients’ overall condition as “very much improved” or “much improved,” and more than 75% of patients (79.3% vs 78.9%) were “very satisfied” or “somewhat satisfied” with their treatment. In the tapentadol IR and oxycodone IR groups, respectively, 52.3% (168/321) and 58.0% (188/324) of patients reported at least one treatment-emergent adverse event (TEAE); the most common (≥ 10%) TEAEs were vomiting (15.9% vs 24.7%), nausea (15.9% vs 20.7%), and dizziness (11.8% vs 10.5%). Vomiting (odds ratio [95% CI], 1.74 [1.17 - 2.57]) and constipation (3.43 [1.45 - 8.11]) were significantly more likely to occur in the oxycodone IR treatment group. Two (0.6%) patients in the tapentadol IR group and 3 (0.9%) patients in the oxycodone IR group experienced treatment-emergent serious adverse events. Limitations: Strict patient monitoring is generally not representative of real-world medical practice; consequently, higher incidences of TEAEs may have been reported than would be expected in a typical practice setting; it is anticipated that this bias would be similar for both treatment groups. Conclusions: This head-to-head study demonstrated that tapentadol IR had comparable analgesic efficacy and overall safety to that of oxycodone IR for the relief of moderate to severe, acute LBP and associated radicular leg pain when using flexible dosing regimens that reflect typical use in clinical practice; however, tapentadol IR demonstrated a better gastrointestinal tolerability profile, particularly for the common opioid-related TEAEs of vomiting and constipation. Clinical Trial Registration: NCT00986180 Key words: Tapentadol, oxycodone, acute low back pain, radicular leg pain, neuropathic pain, flexible dosing, radiculopathy, gastrointestinal tolerability

How the psychosocial context of clinical trials differs from usual care: A qualitative study of acupuncture patients

BackgroundQualitative studies of participants' experiences in randomised clinical trials (RCTs) suggest that the psychosocial context of treatment in RCTs may be quite different to the psychosocial context of treatment in usual practice. This is important, as the psychosocial context of treatment is known to influence patient outcomes in chronic illness. Few studies have directly compared the psychosocial context of treatment across RCTs and usual practice. In this study, we explored differences in psychosocial context between RCT and usual practice settings, using acupuncture as our model.MethodsWe undertook a secondary analysis of existing qualitative interviews with 54 patients. 27 were drawn from a study of western and traditional acupuncture in usual practice (for a range of painful conditions). 27 were drawn from a qualitative study nested in an RCT of western acupuncture for osteoarthritis of the hip or knee. We used qualitative analysis software to facilitate an inductive thematic analysis in which we identified three main themes.ResultsIn usual practice, starting acupuncture was more likely to be embedded in an active and ongoing search for pain relief, whereas in the RCT starting acupuncture was opportunistic. Usual practice patients reported few uncertainties and these had minimal consequences for them. In the RCT, patients experienced considerable uncertainties about their treatment and its effectiveness, and were particularly concerned about whether they were receiving real (or fake) acupuncture. Patients stopped acupuncture only at the end of the fixed course of treatment in the RCT, which was similar to those receiving acupuncture in the public sector National Health Service (NHS). In comparison, private sector patients re-evaluated and re-negotiated treatments particularly when starting to use acupuncture.ConclusionsDifferences in psychosocial context between RCTs and usual practice could reduce the impact of acupuncture in RCT settings and/or lead to under-reporting of benefit by patients in trials. New trial designs that ensure participants' experiences are similar to usual practice should minimise differences in psychosocial context and help attenuate these potentially confounding effects.

COX-2 inhibitors and their role in gynecology.

This review summarizes current knowledge about the roles of cyclooxygenases and prostaglandins in reproductive medicine. With the development of COX-2 specific inhibitors, new therapeutic options are available to obstetricians and gynecologists, offering better-tolerated alternatives to conventional NSAIDs. The analgesic effectiveness of COX-2 specific inhibitors is well established, and they are already in use in a range of painful conditions. Both celecoxib and valdecoxib are indicated for the treatment of primary dysmenorrhea, and may be effective in postoperative pain, including hysterectomy, and pain associated with endometriosis. There is also speculation that COX-2 specific inhibitors may be effective tocolytic agents without the risks to the fetus seen with conventional NSAIDs. The role of COX-2 in oncogenesis is also under investigation, and COX-2 specific inhibitors may eventually be used in the prevention and treatment of gynecologic malignancies. Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader will be able to describe the two types of cylooxygenase enzymes (COX), to list the effects and side effects of NSAIDs and COX-2 medications, and to outline the various changes in COX expression during pregnancy.