Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0423716 (Neuropathic pain)
 1,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropathic pain remains a large unmet medical need. A number of therapeutic options exist, but efficacy and tolerability are less than satisfactory. Based on animal models and limited data from human patients, the pain and hypersensitivity that characterize neuropathic pain are associated with spontaneous discharges of normally quiescent nociceptors. Sodium channel blockers inhibit this spontaneous activity, reverse nerve injury-induced pain behavior in animals and alleviate neuropathic pain in humans. Several sodium channel subtypes are expressed primarily in sensory neurons and may contribute to the efficacy of sodium channel blockers. In this report, the authors review the current understanding of the role of sodium channels and of specific sodium channel subtypes in neuropathic pain signaling.
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PMID:Blocking sodium channels to treat neuropathic pain. 1729 89

Neuropathic pain is defined by the International Association for Pain research as a pain associated to a primary lesion or a dysfunction of the central or peripheral system. Over the past few years the causes of the neuropathic pain were not known and there were not good treatments for it, now we have a better knowledge of the physiopathological aspects and there is a wider diffusion of the research for target aimed therapies. The physiologic genesis of nervous messages occurs exclusively in skin sensorial endings or in nerve tissues as a consequence of an adequate sensorial stimulus and depends on the quick variations of the electric potential difference at the endings of ionic membranes. These variations of even 500 V a second are possible because of the presence of ionic channels. In neuropathic pain impulses can be originated even from ectopic sites. Ectopic discharges originated in a peripheral neuropathic system have an important role in the early stage of neuropathic pain development in two different ways. First they give an excess of spontaneous and evoked electric impulses to the central nervous system, causing a primitive neuropathic pain signal; then the ectopic activity develops and maintains the central sensitisation process. All this amplifies the afferent signals deriving from residual efferents that go on innerving cutaneous areas damaged and partly disnerved, causing tactile allodynie. Sodium channels are the greatest responsible for electrogenesis, that is the basis of the action potential generation and its propagation. Action potential begins after a depolarization such that it could cause a membrane transitory modification, turning prevalently permeable to Na+ more than to K+ as during a release phase. Neuropathy generates a local accumulation of sodium channels, with a consequent increase of density. This remodel seems to be the basis of neuro hyperexecitably. Calcium channels have also an important role in cell working. Intracellular calcium increase contributes to depolarization processes, through kinase and determines the phosphorylation of membrane proteins that can make powerful the efficacy of the channels themselves. In the future new diagnostic opportunities of physiopathologist mechanism leading to neuropathic pain will allow treatments aimed at specific molecular changes of ionic channels.
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PMID:Ionic channels and neuropathic pain: physiopathology and applications. 1820 77

Neuropathic pain usually is persistent and no effective treatment. ATP plays an important role in the initiation of pain. P2X(3) receptors are localized in the dorsal root ganglion (DRG) neurons and activated by extracellular ATP. Sodium ferulate (SF) is an active principle from Chinese herbal medicine and has anti-inflammatory activities. This study observed the effects of SF on the nociceptive facilitation of the primary sensory afferent after chronic constriction injury (CCI) mediated by P2X(3) receptor. In this study, the content of ATP in DRG neurons was measured by high-performance liquid chromatography (HPLC). P2X(3) agonist-activated currents in DRG neurons was recorded by the whole-cell patch-clamp skill. The expression of P2X(3) mRNA in DRG neurons was analyzed by in situ hybridization. The ATP content of DRG was increased after CCI. In CCI rats treated with SF, the content of ATP in DRG neurons was reduced. SF decreased the increment of P2X(3) agonist-activated currents and P2X(3) mRNA expression in DRG neurons during CCI. SF may inhibit the initiation of pain and primary afferent sensitization mediated by P2X(3) receptor during CCI.
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PMID:Role of sodium ferulate in the nociceptive sensory facilitation of neuropathic pain injury mediated by P2X(3) receptor. 1880 51

Neuropathic pain is usually persistent and there is no effective treatment. Activation of P2X(3) receptor subtype in primary sensory neurons is involved in neuropathic pain. Sodium ferulate (SF) is an active principle from Chinese herbal medicine and has anti-inflammatory activities. This study observed the effects of SF on the hyperalgesia mediated by P2X(3) receptor of rats after chronic constriction injury (CCI). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured and the expression of P2X(3) receptor immunoreactivity and protein in dorsal root ganglion (DRG) neurons was analyzed by immunohistochemistry and western blotting. In CCI rats treated with SF, the MWT and TWL were increased compared with CCI rats treated with normal saline. The expression of P2X(3) receptor in DRG neurons was increased after CCI. In CCI rats treated with SF, the up-regulated expression of P2X(3) receptor in DRG neurons was reduced. SF may reduce the thermal and mechanical hyperalgesia in CCI rat model by decreasing the pain transmitted by primary afferant neurons mediated by P2X(3) receptor during the chronic neuropathic pain injury.
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PMID:Effect of sodium ferulate on the hyperalgesia mediated by P2X3 receptor in the neuropathic pain rats. 3103 Aug 95

Neuropathic pain is commonly associated with lesion or disease of the somatosensory system and often reflected as indicator of impaired life. Although the central nervous system is main regulator of pain but for initiation and maintenance of the neuropathic pain is regulated by peripheral nervous system. Sodium channels particularly Nav1.7, Nav1.8, Nav 1.9 are key stake holders in the peripheral neuropathy, activation of these sodium channels might lead to genesis and propagation. Flavonoids and polyphenols showed promising effects in neuropathic pain. Here we are reporting In silico analysis of some selected flavonoids and polyphenols on sodium activated voltage channel 1.7 to explore the structural fragments required for binding. Results indicated Baicalin, Butrin, Dihydromonospermoside, Icariin, Isocoreopsin and Isosaponarin are showing promising docking score with sodium activated voltage channel 1.7 than other compounds. Structural modification of these promising leads keeping pharamcophoric requirement intact may yield potent Nav1.7 inhibitors for peripheral pain management. Communicated by Ramaswamy H. Sarma.
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PMID:In silico analysis of polyphenols and flavonoids for design of human Nav1.7 inhibitors. 3268 94