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The US National Pain Strategy focused attention on high-impact chronic pain and its restrictions. Although many interventions have been studied for chronic low-back pain, results are typically reported for heterogeneous samples. To better understand chronic pain and target interventions to those who most need care, more granular classifications recognizing chronic pain's impact are needed.
Learn More >Cannabinoids are proposed in a wide array of medical indications. Yet, the evaluation of adverse effects in controlled clinical studies, following the evidence-based model, has partly been by-passed. On the other hand, studies on the consequences of recreational use of cannabis and experimental studies bring some insights on the potential long-term consequences of cannabinoids use.
Learn More >To determine the association of medical marijuana legalization with prescription opioid utilization.
Learn More >Offset analgesia (OA) is the disproportionate decrease in pain experience following a slight decrease in noxious heat stimulus intensity. Here we tested whether sequential offsets would allow noxious temperatures to be reached with little or no perception of pain. Forty-eight participants continuously rated their pain experience during trials containing trains of heat stimuli delivered by peltier thermode. Stimuli were adjusted through either step-wise sequential increases of 2 C and decreases of 1 C or direct step increases of 1 C, up to a maximum of 46 C. Step durations (1, 2, 3, or 6 s) varied by trial. Pain ratings generally followed presented temperature, regardless of step condition or duration. For 6 s steps, offset analgesia was observed after each decrease, but the overall pain trajectory was unchanged. We found no evidence that sequential offsets could allow for little pain perception during noxious temperature presentation.
Learn More >Increasing pain during physical activity is as an important, but often poorly assessed, barrier to engaging in activity-based rehabilitation among people with chronic musculoskeletal pain. Preliminary work has addressed this problem by developing new clinical measures of sensitivity to physical activity (SPA). Indices of SPA are generated by evaluating how pain changes in relation to brief physical tasks. Three strategies have been identified for structuring SPA-related physical tasks (self-paced, standardized, and tailored). This cross-sectional study aimed to comparatively estimate the extent of the three SPA tasks' evoked pain responses, predictive value of pain severity and pain interference, and their underlying psychological and sensory constructs, among 116 adults with chronic musculoskeletal pain.
Learn More >Nonclinical safety evaluation of erenumab, a CGRP receptor inhibitor for the prevention of migraine.
Calcitonin gene-related peptide (CGRP) and its receptor have been implicated as a key mediator in the pathophysiology of migraine. Thus, erenumab, a monoclonal antibody antagonist of the CGRP receptor, administered as a once monthly dose of 70 or 140 mg has been approved for the preventive treatment of migraine in adults. Due to the species specificity of erenumab, the cynomolgus monkey was used in the pharmacology, pharmacokinetics, and toxicology studies to support the clinical program. There were no effects of erenumab on platelets in vitro (by binding, activation or phagocytosis assays). Specific staining of human tissues with erenumab did not indicated any off-target binding. There were no erenumab-related findings in a cardiovascular safety pharmacology study in cynomolgus monkeys or in vitro in human isolated coronary arteries. Repeat-dose toxicology studies conducted in cynomolgus monkeys at dose levels up to 225 mg/kg (1 month) or up to 150 mg/kg (up to 6 months) with twice weekly subcutaneous (SC) doses showed no evidence of erenumab-mediated adverse toxicity. There were no effects on pregnancy, embryo-fetal or postnatal growth and development in an enhanced pre-postnatal development study in the cynomolgus monkey. There was evidence of placental transfer of erenumab based on measurable serum concentrations in the infants up to 3 months post birth. The maternal and developmental no-observed-effect level (NOEL) was the highest dose tested (50 mg/kg SC Q2W). These nonclinical data in total indicate no safety signal of concern to date and provide adequate margins of exposure between the observed safe doses in animals and clinical dose levels.
Learn More >The majority of self-management interventions are designed with a narrow focus on patient skills and fail to consider their potential as "catalysts" for improving care delivery. A project was undertaken to develop a patient self-management resource to support evidence-based, person-centered care for cancer pain and overcome barriers at the levels of the patient, provider, and health system.
Learn More >Psychological and personality factors, socioeconomic status, and brain properties all contribute to chronic pain but have essentially been studied independently. Here, we administered a broad battery of questionnaires to patients with chronic back pain (CBP) and collected repeated sessions of resting-state functional magnetic resonance imaging (fMRI) brain scans. Clustering and network analyses applied on the questionnaire data revealed four orthogonal dimensions accounting for 56% of the variance and defining chronic pain traits. Two of these traits-Pain-trait and Emote-trait-were associated with back pain characteristics and could be related to distinct distributed functional networks in a cross-validation procedure, identifying neurotraits. These neurotraits showed good reliability across four fMRI sessions acquired over five weeks. Further, traits and neurotraits all related to the income, emphasizing the importance of socioeconomic status within the personality space of chronic pain. Our approach is a first step in providing metrics aimed at unifying the psychology and the neurophysiology of chronic pain applicable across diverse clinical conditions.
Learn More >Residual lower-limb pain after low back surgery (postsurgical sciatica) and complex regional pain syndrome (CRPS) involving a lower limb are separate conditions but may share some mechanisms (eg, tissue inflammation, neuroimmune disturbances, and central neuroplasticity). As adrenergically evoked pain contributes, in part, to CRPS, whether an adrenergic mechanism also contributes to postsurgical sciatica was investigated in this study. Immunohistochemistry was used to identify α1-adrenoceptors (α1-AR) on nerve fibres and other targets in the affected and contralateral skin of 25 patients with postsurgical sciatica, and α1-AR expression was investigated in relation to pain and pinprick hyperalgesia after intradermal injection of the α1-AR agonist phenylephrine. In addition, quantitative sensory testing was performed on all 4 limbs and on each side of the forehead. α1-AR expression was greater in keratinocytes (but not blood vessels or nerve fibres) in the symptomatic than contralateral leg, and dermal nerve fibre density was reduced in both legs. However, distal adrenergic involvement in pain in postsurgical sciatica seems unlikely, as neither heightened α1-AR expression in keratinocytes nor reduced dermal nerve fibre density were associated with pain or hyperalgesia to intradermal phenylephrine injection. Sensitivity to pressure-pain, pinprick, and cold-pain was greater in the ipsilateral than contralateral forehead of the entire cohort, but sensory disturbances were most pronounced in patients with additional CRPS-like features. Together, these findings suggest that bilateral distal neuropathy and central neuroplastic changes are involved not only in the pathophysiology of CRPS but also in postsurgical sciatica. This may have treatment implications for patients with postsurgical sciatica.
Learn More >The spinal administration of opioids can cause intense pruritisInteractions between specific μ-opioid receptor isoforms and the gastrin releasing peptide receptor in spinal tissues likely mediate morphine-induced pruritus WHAT THIS ARTICLE TELLS US THAT IS NEW: Human spinal cord tissue expresses the 1Y isoform of the μ-opioid receptor, and that isoform functionally interacts with the gastrin releasing peptide receptor to cause cellular calcium influxBlocking interactions between the 1Y isoform and the gastrin releasing peptide receptor does not reduce opioid analgesiaEliminating interactions between the 1Y isoform and the gastrin releasing peptide receptor or reducing 1Y isoform activation may reduce opioid-induced pruritis BACKGROUND:: Although spinal opioids are safe and effective, pruritus is common and distressing. The authors previously demonstrated in mouse spinal cord that interactions between μ-opioid receptor isoform 1D and gastrin releasing peptide receptor mediate morphine-induced scratch. The C-terminal of 1D inhibits morphine-induced scratch without affecting analgesia. The authors hypothesize that human spinal cord also contains itch-specific μ-opioid receptor isoforms which interact with gastrin releasing peptide receptor.
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