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Among adults with persistent post-amputation pain, increased amputated-region pain sensitivity may reflect peripheral sensitization or indicate underlying central sensitization. To determine whether underlying central sensitization may contribute to increased pain sensitivity in this population, this study compared clinical signs and symptoms associated with central sensitization between adults with post-amputation pain who demonstrate or lack increased amputated-region sensitivity (as compared to reference data).
Learn More >Fibromyalgia is a central sensitivity syndrome that presents with chronic pain, fatigue, cognitive dysfunction, and disordered sleep. The pathophysiology which due to multisensory hypersensitivity of the central nervous system involves neuronal excitability leading to central sensitization. Treatments of the challenges associated with the complexities of fibromyalgia involve combinations of pharmacological and non-pharmacological therapeutic approaches which often offer limited benefit. Potassium (K+) channels play a fundamental role in establishing and maintaining stability of neuronal activity. The large molecular diversity and distribution of K+ channels support involvement in a broad range of physiological functions. In nociceptive pathways, neuronal hyperexcitability leading to pain sensation has been associated with reduced function of K+ channels and loss of cellular control. This article reviews the evidence of involvement of K+ channels in fibromyalgia. A potential role both in the pathophysiological processes responsible for the symptoms of fibromyalgia and as therapeutic targets for the management of the condition is considered.
Learn More >Lichen simplex chronicus is a form of chronic localized pruritus with a secondary dermatitis, and one of the most common types of chronic itch conditions, estimated to affect more than 10% of the general population. However, despite its prevalence and burden, there has been limited research into the pathogenesis and aetiology of lichen simplex chronicus, which, historically, made it a challenging condition to treat. In recent years, our understanding of this condition, along with that of pruritus and the itch-scratch cycle, has increased greatly, enabling a substantial increase in treatment options. In addition, there are several new promising treatments currently in development and trials. This article discusses the definition, epidemiology, clinical characteristics, pathophysiology, and current therapeutic options for lichen simplex chronicus, in order to highlight recent advancements in this field.
Learn More >Peripheral nerve stimulation (PNS) has been utilized for over 50 years with accumulating evidence of efficacy in a variety of chronic pain conditions. The level and strength of evidence supporting the use of PNS for peripheral neuropathic pain remains unclear. The purpose of this review is to synthesize data from prospective studies on the efficacy of PNS for neuropathic pain as it pertains to pain intensity, neurological deficits/neuropathy (e.g., weakness, sensory deficits, gait/balance), and other secondary outcomes (quality of life, satisfaction, emotional functioning, and adverse events). In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, this review identified articles from MEDLINE(R), EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. Overall, per the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, pooled results demonstrate very low quality or low quality of evidence supporting modest to substantial improvement in pain and neurological function after PNS implantation for treatment of peripheral neuropathic pain. PNS for phantom limb pain was the only indication that had moderate level evidence. Future prospective and well-powered studies are warranted to assess the efficacy of PNS for peripheral neuropathic pain.
Learn More >Here we studied spinal neurotransmitter mechanisms involved in the reduction of mechanical hypersensitivity by inhibition of the amygdaloid central nucleus (CeA) in male and female rats with spared nerve injury (SNI) model of neuropathy. SNI induced mechanical hypersensitivity that was stronger in females. Reversible blocking of the CeA with muscimol (GABA receptor agonist) induced a reduction of mechanical hypersensitivity that did not differ between males and females. Following spinal co-administration of atipamezole (α-adrenoceptor antagonist), the reduction of mechanical hypersensitivity by CeA muscimol was attenuated more in males than females. In contrast, following spinal co-administration of raclopride (dopamine D2 receptor antagonist) the reduction of hypersensitivity by CeA muscimol was attenuated more in females than males. The reduction of mechanical hypersensitivity by CeA muscimol was equally attenuated in males and females by spinal co-administration of WAY-100635 (5-HT receptor antagonist) or bicuculline (GABA receptor antagonist). The CeA muscimol induced attenuation of ongoing pain-like behavior (conditioned place preference test) that was reversed by spinal co-administration of atipamezole in both sexes. The results support the hypothesis that CeA contributes to mechanical hypersensitivity and ongoing pain-like behavior in SNI males and females. Disinhibition of descending controls acting on spinal α-adrenoceptors, 5-HT, dopamine D2 and GABA receptors provides a plausible explanation for the reduction of mechanical hypersensitivity by CeA block in SNI. The involvement of spinal dopamine D2 receptors and α-adrenoceptors in the CeA muscimol-induced reduction of mechanical hypersensitivity is sexually dimorphic, unlike that of spinal α-adrenoceptors in the reduction of ongoing neuropathic pain.
Learn More >To ascertain whether intravenous infusion of calcitonin gene-related peptide (CGRP) can induce migraine-like headache in people with persistent post-traumatic headache attributed to mild traumatic brain injury (TBI) and no pre-existing migraine.
Learn More >In this meta-analysis, we aim to compare ketamine use versus a control group (saline solution) during induction of anesthesia in adolescent idiopathic scoliosis patients undergoing fusion surgery in terms of postoperative opioid consumption, pain control, and side effects.
Learn More >α2δ-1 (encoded by the gene) is a newly discovered NMDA receptor-interacting protein and is the therapeutic target of gabapentinoids (e.g., gabapentin and pregabalin), frequently used for treating patients with neuropathic pain. Nerve injury causes sustained α2δ-1 upregulation in the dorsal root ganglion (DRG), which promotes NMDA receptor synaptic trafficking and activation in the spinal dorsal horn, a hallmark of chronic neuropathic pain. However, little is known about how nerve injury initiates and maintains the high expression level of α2δ-1 to sustain chronic pain. Here, we show that nerve injury caused histone hyperacetylation and diminished enrichment of histone deacetylase-2 (HDAC2), but not HDAC3, at the promoter in the DRG. Strikingly, knockdown or conditional knockout in DRG neurons in male and female mice consistently induced long-lasting mechanical pain hypersensitivity, which was readily reversed by blocking NMDA receptors, inhibiting α2δ-1 with gabapentin, or disrupting the α2δ-1-NMDA receptor interaction at the spinal cord level. deletion in DRG neurons increased histone acetylation levels at the promoter, upregulated α2δ-1 in the DRG, and potentiated α2δ-1-dependent NMDA receptor activity at primary afferent central terminals in the spinal dorsal horn. Correspondingly, knockdown-induced pain hypersensitivity was blunted in knockout mice. Thus, our findings reveal that HDAC2 functions as a pivotal transcriptional repressor of neuropathic pain via constitutively suppressing α2δ-1 expression and ensuing presynaptic NMDA receptor activity in the spinal cord. HDAC2 enrichment levels at the promoter in DRG neurons constitute a unique epigenetic mechanism that governs acute-to-chronic pain transition.Excess α2δ-1 proteins produced after nerve injury directly interact with glutamate NMDA receptors to potentiate synaptic NMDA receptor activity in the spinal cord, a prominent mechanism of nerve pain. Because α2δ-1 upregulation after nerve injury is long-lasting, gabapentinoids relieve pain symptoms only temporarily. Our study demonstrates for the first time the unexpected role of intrinsic HDAC2 at the α2δ-1 gene promoter in limiting α2δ-1 gene transcription, NMDA receptor-dependent synaptic plasticity, and chronic pain development after nerve injury. These findings challenge the prevailing view about the role of general HDAC activity in promoting chronic pain. Restoring the repressive HDAC2 function and/or reducing histone acetylation at the α2δ-1 gene promoter in primary sensory neurons could lead to long-lasting relief of nerve pain.
Learn More >The aim of this study was to describe cases of patients with presumable dysimmune small-fiber neuropathy (SFN)-related neuropathic corneal pain (NCP), presenting with autoantibodies against trisulfated heparin disaccharide (TS-HDS) or fibroblast growth factor receptor-3 (FGFR-3).
Learn More >Prostaglandin E is classically considered a major mediator of inflammatory pain, by acting on neuronal G protein-coupled EP2 and EP4 receptors. However, the neuronal EP3 receptor, colocalized with EP2 and EP4 receptor, is G protein-coupled and antagonises the pronociceptive prostaglandin E effect. Here we investigated the cellular signalling mechanisms by which the EP3 receptor reduces EP2 and EP4 receptor-evoked pronociceptive effects in sensory neurons.
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