Pain
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Randomized Controlled Trial
Radiofrequency treatment relieves chronic knee osteoarthritis pain: a double-blind randomized controlled trial.
Chronic osteoarthritis (OA) pain of the knee is often not effectively managed with current non-pharmacological or pharmacological treatments. Radiofrequency (RF) neurotomy is a therapeutic alternative for chronic pain. We investigated whether RF neurotomy applied to articular nerve branches (genicular nerves) was effective in relieving chronic OA knee joint pain. ⋯ No patient reported a post-procedure adverse event during the follow-up period. RF neurotomy of genicular nerves leads to significant pain reduction and functional improvement in a subset of elderly chronic knee OA pain, and thus may be an effective treatment in such cases. Further trials with larger sample size and longer follow-up are warranted.
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Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. ⋯ Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.
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Randomized Controlled Trial
Impact of responder definition on the enriched enrollment randomized withdrawal trial design for establishing proof of concept in neuropathic pain.
The objective of this study was to evaluate how enrichment for responders increases assay sensitivity in an enriched enrollment randomized withdrawal (EERW) proof-of-concept (POC) study in neuropathic pain. Adults with moderate to severe peripheral neuropathic pain entered a 3- to 4-day screening period, followed by a 12-day titration to the highest tolerated dose that provided pain control (pregabalin 50-200mg t.i.d.), and then a 9-day maintenance period. Subjects were stratified as primary responders (⩾30%), secondary responders (⩾10% to <30%), or nonresponders (<10%) based on decrease in pain intensity and were randomized to placebo or pregabalin during the randomized withdrawal period. ⋯ The highest ES (1.68) was demonstrated for the endpoint time-to-efficacy-failure seen in primary responders with painful diabetic neuropathy. The EERW trial design using time-to-efficacy-failure may provide a sensitive and efficient method to conduct POC studies of novel therapies in patients with neuropathic pain. Enriching a study population with patients who have achieved a 30% decrease in pain with an investigational therapy, and using time-to-efficacy-failure during the randomized withdrawal phase as the primary endpoint, can be used for a proof-of-concept study to optimize assay sensitivity and efficiently determine the analgesic potential of a new treatment for neuropathic pain.
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In human pain experiments, as well as in clinical settings, subjects are often asked to assess pain using scales (eg, numeric rating scales). Although most subjects have little difficulty in using these tools, some lack the necessary basic cognitive or motor skills (eg, paralyzed patients). Thus, the identification of appropriate nonverbal measures of pain has significant clinical relevance. ⋯ We conclude that at least for male subjects, HR provides a better predictor of pain perception than SC, but that data should be averaged over several stimulus presentations to achieve consistent results. Nevertheless, variability among studies, and the indication that gender of both the subject and experimenter could influence autonomic results, lead us to advise caution in using autonomic or any other surrogate measures to infer pain in individuals who cannot adequately report their perception. Skin conductance is more sensitive to detect within-subject perceptual changes, but heart rate appears to better predict pain ratings at the group level.