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The advent of anti-CGRP medications is an example of translational research made real. Pioneering research by Drs. Lars Edvinsson and Peter Goadsby has yielded the monoclonal antibody therapeutics and will likely also result in the gepants. The availability of MABs represents a watershed moment in the treatment of migraine. These medications have specificity, as they were designed for primary migraine prevention. They work across a group of wide therapeutic targets, episodic migraine, chronic migraine, medication-overuse headache, and episodic cluster headache. They separate from placebo within 1 week, and often show clinical effects within a month or less. They have tolerability similar to placebo. There has been no significant or worrisome safety signal thus far in their use. They manifest unprecedented responder rates at ≥ 75% and even 100%. They lower all acute medication use and can convert patients from chronic migraine to episodic migraine and from acute medication overuse to non-overuse. They work in patients who have already had lack of success with at least 2-4 previous preventive medications. Pent-up demand for designer, well-tolerated, and effective migraine preventive medication in the USA has resulted in more than 100,000 individual patients prescribed erenumab from May to December of 2018, and the numbers continue to increase. The preventive treatment of migraine in the USA has shifted dramatically, and is likely to do so in the rest of the world as well.
Learn More >High frequency electrical stimulation (HFS) of skin nociceptors triggers central sensitization (CS), manifested as increased pinprick sensitivity of the skin surrounding the site of HFS. Our aim was to assess the effect of CS on pinprick-evoked pupil dilation responses (PDRs) and pinprick-evoked brain potentials (PEPs). We hypothesized that the increase in the positive wave of PEPs following HFS would result from an enhanced pinprick-evoked phasic response of the locus coeruleus-noradrenergic system (LC-NS), indicated by enhanced PDRs. In fourteen healthy volunteers, 64 and 96 mN pinprick stimuli were delivered to the left and right forearms, before and twenty minutes after applying HFS to one of the two forearms. Both PEPs and pinprick-evoked PDRs were recorded. After HFS, pinprick stimuli were perceived as more intense at the HFS treated arm compared to baseline and control site, and this increase was similar for both stimulation intensities. Importantly, the pinprick-evoked PDR was also increased and the increase was stronger for 64 as compared to 96 mN stimulation. This is in line with our previous results showing a stronger increase of the PEP positivity at 64 vs. 96 mN stimulation and suggests that the increase in PEP positivity observed in previous studies could relate, at least in part, to enhance LC-NS activity. However, there was no increase of the PEP positivity in the present study, indicating that enhanced LC-NS activity is not the only determinant of the HFS-induced enhancement of PEPs. Altogether, our results indicate that PDRs are more sensitive for detecting CS than PEPs.
Learn More >This article presents the results of a parallel-group, non-randomized, controlled study that evaluated the feasibility of an online training program for improving observer detection of facial pain expression.
Learn More >To assess efficacy and safety of lidocaine 700 mg medicated plaster (lidocaine plaster) compared to placebo in patients with moderate to severe chronic post-surgical neuropathic pain (PSNP).
Learn More >Spinal cord stimulation (SCS), based on the gate theory of nociception, has been shown to be effective in the management of chronic pain conditions. While early-generation technology offered many patients improvement in their pain and symptoms, limitations including paresthesia, dependence on mapping, decreased chronological efficacy, and inadequate coverage left many patients with persistent pain and overt therapeutic failure.
Learn More >The traditional translational approach in neuropathic pain research has mainly consisted to date in translating basic findings from animal models of nerve injury to the clinic. Because of the difficulty to extrapolate mechanisms from animals to humans, an inverse translational approach ("top-down") has been advocated and contributed to the development of therapy. In particular, a number of treatments such as neurostimulation techniques have been initially assessed in patients and then translated to animal models for further investigation of their mechanisms. Therapeutic approaches based on an in-depth assessment of sensory phenotypes, suggestive of mechanisms, have also been implemented. The biggest trend in recent translational research is to investigate mechanisms or predict therapeutic response in patients by integrating multimodal approaches. The present narrative review emphasizes these various aspects of translational research in neuropathic pain.
Learn More >The primary objective of preclinical pain research is to improve the treatment of pain. Decades of research using pain-evoked tests has revealed much about mechanisms but failed to deliver new treatments. Evoked pain-tests are often limited because they ignore spontaneous pain and motor or disruptive side effects confound interpretation of results. New tests have been developed to focus more closely on clinical goals such as reducing pathological pain and restoring function. The objective of this review is to describe and discuss several of these tests. We focus on: Grimace Scale, Operant Behavior, Wheel Running, Burrowing, Nesting, Home Cage Monitoring, Gait Analysis and Conditioned Place Preference/ Aversion. A brief description of each method is presented along with an analysis of the advantages and limitations. The pros and cons of each test will help researchers identify the assessment tool most appropriate to meet their particular objective to assess pain in rodents. These tests provide another tool to unravel the mechanisms underlying chronic pain and help overcome the translational gap in drug development.
Learn More >Selective N-methyl-d-aspartate receptor subunit 2B (NR2B) antagonists show potential as analgesic drugs, and do not cause side effects associated with non-selective N-methyl-d-aspartate (NMDA) antagonists. Using a scaffold-hopping approach, we previously identified isoxazole derivative 4 as a potent selective NR2B antagonist. In this study, further scaffold hopping of isoxazole derivative 4 and optimization of its pharmacokinetic profile led to the discovery of the orally bioavailable compound 6v. In a rat study of analgesia, 6v demonstrated analgesic effects against neuropathic pain.
Learn More >This study aims to investigate the psychometric properties (component structure, reliability, and construct validity) of the Headache-Specific Locus of Control scale in several clinical migraine populations.
Learn More >Most patients with migraine report associated neck pain. Whether neck pain is a symptom of migraine or an indicator for associated cervical musculoskeletal impairment has not yet been determined. Physical examination tests to detect cervical impairments in people with headache have been suggested, but results have not been evaluated systematically and combined in meta-analyses.
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