Articles: neuropathic-pain.
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Ambroxol is a multifaceted drug with primarily mucoactive and secretolytic actions, along with anti-inflammatory, antioxidant, and local anaesthetic properties. It has a long history of use in the treatment of respiratory tract diseases and has shown to be efficacious in relieving sore throat. In more recent years, ambroxol has gained interest for its potential usefulness in treating neuropathic pain. ⋯ With its well-established safety profile, extensive preclinical and clinical drug data, and early evidence of clinical effectiveness, ambroxol is an old drug worthy of further investigation for repurposing. As a patent-expired drug, a push is needed to progress the drug to clinical trials for neuropathic pain. We encourage the pharmaceutical industry to look at patented drug formulations and take an active role in bringing an optimized version for neuropathic pain to market.
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An ACVR1 activating mutation causes neuropathic pain and sensory neuron hyperexcitability in humans.
Altered bone morphogenetic protein (BMP) signaling is associated with many musculoskeletal diseases. However, it remains unknown whether BMP dysfunction has direct contribution to debilitating pain reported in many of these disorders. Here, we identified a novel neuropathic pain phenotype in patients with fibrodysplasia ossificans progressiva (FOP), a rare autosomal-dominant musculoskeletal disorder characterized by progressive heterotopic ossification. ⋯ Although there was no major effect of ACVR1 R206H on differentiation and maturation of nociceptive sensory neurons (iSNs) derived from FOP induced pluripotent stem cells, both intracellular and extracellular electrophysiology analyses of the ACVR1 R206H iSNs displayed ACVR1-dependent hyperexcitability, a hallmark of neuropathic pain. Consistent with this phenotype, we recorded enhanced responses of ACVR1 R206H iSNs to TRPV1 and TRPA1 agonists. Thus, activated ACVR1 signaling can modulate pain processing in humans and may represent a potential target for pain management in FOP and related BMP pathway diseases.
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Given that the incidence of cancer is dramatically increasing nowadays, cancer-related neuropathic pain including tumor-related and therapy-related pain gradually attracts more attention from researchers, which basically behaves as a metabolic-neuro-immune disorder with worse clinical outcomes and prognosis. Among various mechanisms of neuropathic pain, the common underlying one is the activation of inflammatory responses around the injured or affected nerve(s). Innate and adaptive immune reactions following nerve injury together contribute to the regulation of pain. ⋯ Of interest, these immune cells in tumor microenvironment exert potent functions in promoting neuropathic pain through different signaling pathways. To this end, this review mainly focuses on the contribution of different types of immune cells to cancer-related neuropathic pain, aims to provide a comprehensive summary of how these immune cells derived from the certain tumor microenvironment participate in the pathogenesis of neuropathic pain. Furthermore, the clarification of roles of various immune cells in different tumor immune microenvironments associated with certain cancers under neuropathic pain states constitutes innovative biology that takes the pain field in a different direction, and thereby provides more opportunities for novel approaches for the prevention and treatment of cancer-related neuropathic pain.
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Neuropathic pain is a common dose-limiting side effect of oxaliplatin, which hampers the effective treatment of tumors. Here, we found that upregulation of transcription factor NFATc2 decreased the expression of Beclin-1, a critical molecule in autophagy, in the spinal dorsal horn, and contributed to neuropathic pain following oxaliplatin treatment. ⋯ Further assays revealed that NFATc2 regulated histone H4 acetylation and methylation in the TSC2 promoter site 1 in rats' dorsal horns with oxaliplatin treatment. These results suggested that NFATc2 mediated the epigenetic downregulation of the TSC2/Beclin-1 autophagy pathway and contributed to oxaliplatin-induced mechanical allodynia, which provided a new therapeutic insight for chemotherapy-induced neuropathic pain.
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Previous studies have confirmed the relationship between chloride homeostasis and pain. However, the role of sodium potassium chloride co-transporter isoform 1 (NKCC1) in dorsal horn and dorsal root ganglion neurons (DRGs) in spinal cord injury (SCI)-induced neuropathic pain (NP) remains inconclusive. Therefore, we aimed to explore whether suppression of NKCC1 in the spinal cord and DRGs alleviate the NP of adult rats with thoracic spinal cord contusion. ⋯ Our results revealed that NKCC1 protein expression in the spinal cord and DRGs was significantly up-regulated in rats with SCI. Intraperitoneal treatment of bumetanide (an NKCC1 inhibitor) reversed the expression of NKCC1 in the dorsal horn and DRGs and ameliorated mechanical ectopic pain and thermal hypersensitivities in the SCI rats. Our study demonstrated the occurrence of NKCC1 overexpression in the spinal cord and DRGs in a rodent model of NP and indicated that changes in the peripheral nervous system also play a major role in promoting pain sensitization after SCI.