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The chronic pain syndrome inherited erythromelalgia (IEM) is attributed to mutations in the voltage-gated sodium channel (Nav) 1.7. Still, recent studies targeting Nav1.7 in clinical trials have provided conflicting results. Here, we differentiated induced pluripotent stem cells (iPS cells) from IEM patients with the Nav1.7/I848T mutation into sensory nociceptors. Action potentials in these IEM nociceptors displayed a decreased firing threshold, an enhanced upstroke and afterhyperpolarization, all of which may explain the increased pain experienced by patients. Subsequently, we investigated the voltage dependence of the tetrodotoxin-sensitive Nav activation in these human sensory neurons using a specific pre-pulse voltage protocol. The IEM mutation induced a hyperpolarizing shift of Nav activation which leads to activation of Nav1.7 at more negative potentials. Our results indicate that Nav1.7 is not active during subthreshold depolarizations, but that its activity defines the action potential threshold and contributes significantly to the action potential upstroke. Thus, our model system with iPS cell-derived sensory neurons provides a new rationale for Nav1.7 function and promises to be valuable as a translational tool to profile and develop more efficacious clinical analgesics.
Learn More >Few investigators have developed and tested nonpharmacological interventions for helping persons with sickle cell disease (SCD) manage persistent pain.
Learn More >Vulvodynia is a debilitating, chronic vulvar pain condition. Community-based case-control studies have consistently shown associations between early-life chronic stressors and vulvodynia onset.
Learn More >To determine whether pain-related treatment outcomes, following an online Cognitive Behavioural Therapy (CBT) intervention for chronic pain, were moderated by the pain etiology of a medically explained or unexplained origin.
Learn More >Cutaneous allodynia is a common clinical feature of migraine that has been associated with reduced efficacy of acute migraine treatments and an increased risk of disease progression.
Learn More >Postoperative pain is common and promotes opioid use. Surgical wounds are hypoxic because normal perfusion is impaired. Local wound ischemia and acidosis promote incisional pain. Some evidence suggests that improving oxygen supply to surgical wounds might reduce pain. We therefore tested the hypothesis that supplemental (80% inspired) intraoperative oxygen reduces postoperative pain and opioid consumption.
Learn More >Multiple studies have evaluated the associations between 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and migraine risk with conflicting results. Therefore, we conducted a meta-analysis on this theme.
Learn More >Presentation of pooled analysis of safety data for fremanezumab in patients with chronic (CM) or episodic migraine (EM) from 4 placebo-controlled phase 2b and phase 3 studies.
Learn More >Pelvic pain and vulvar pain are common conditions in women. In this study, we sought to characterize the clinical picture of patients with concurrent pelvic pain and provoked vestibulodynia (PVD).
Learn More >The purpose of this review is to summarize recent findings on conditioned pain modulation (CPM) in humans with a focus on methodology, factors modulating CPM, and the potential for CPM as a clinical marker for pain progression.
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