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 and epileptic seizures bear several similarities, among them is the response to anticonvulsant drugs. It has therefore been hypothesized that epileptiform activity of nociceptive spinal dorsal horn neurons may contribute to paroxysmal forms of neuropathic pain. We used patch-clamp and field potential recordings from young rat spinal cord slices to test if nociceptive dorsal horn structures are indeed able to sustain epileptiform activity. Application of the convulsant 4-aminopyridine (100 microM) evoked epileptiform activity that was most pronounced in superficial dorsal horn and involved nociceptive lamina I neurons with a projection to the brain. The epileptiform activity was dependent on fast excitatory and inhibitory synaptic transmission through ionotropic glutamate receptors and GABA(A) receptors. During epileptiform activity, previously silent polysynaptic pathways from primary afferent C-fibers to superficial dorsal horn neurons were opened. Stimulation of primary afferents at Adelta- and C-fiber intensity interfered with the epileptiform rhythm, suggesting that both affect the same dorsal horn structures. Similar to neuropathic pain, spinal dorsal horn epileptiform activity was much less reduced by classical analgesics than by anticonvulsant agents.
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PMID:Epileptiform activity in rat spinal dorsal horn in vitro has common features with neuropathic pain. 1449 51

Neuropathic pain, a debilitating chronic pain following nerve damage, is a reflection of the aberrant functioning of a pathologically altered nervous system. One hallmark is abnormal pain hypersensitivity to innocuous stimuli (tactile allodynia), for which effective therapy is lacking, and the underlying mechanisms of which remain to be determined. Here we show that Lyn, a member of the Src family kinases (SFKs), plays an important role in the pathogenesis of neuropathic pain. Nerve injury, but not peripheral inflammation, increased immunoreactivity for active SFKs that were autophosphorylated in the kinase domain (phospho-SFK-IR) in spinal microglia. In spinally derived microglial cells, we identified Lyn as the predominant SFK among the five members (Src, Fyn, Yes, Lck, and Lyn) known to be expressed in the CNS. Lyn expression in the spinal cord was highly restricted to microglia, and its level was increased after nerve injury. We found that mice lacking lyn (lyn(-/-)) exhibit a striking reduction in the levels of phospho-SFK-IR and tactile allodynia after nerve injury, without any change in basal mechanical sensitivity or inflammatory pain. Importantly, lyn(-/-) mice displayed impaired upregulation of the ionotropic ATP receptor subtype P2X(4) receptors (P2X(4)R) in the spinal cord after nerve injury, which is crucial for tactile allodynia. Microglial cells from lyn(-/-) mice showed a deficit in their ability to increase P2X(4)R expression in response to fibronectin, a factor implicated as a microglial P2X(4)R upregulator in allodynia. Together, our findings suggest that Lyn may be a critical kinase mediating nerve injury-induced P2X(4)R upregulation and neuropathic pain.
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PMID:Lyn tyrosine kinase is required for P2X(4) receptor upregulation and neuropathic pain after peripheral nerve injury. 1791 63

Neuropathic pain is generally defined as a chronic pain state resulting from peripheral or central nerve injury, or both. An effective treatment for neuropathic pain is still lacking. The NMDA receptor, one type of the ionotropic glutamate receptors, is known to be important for triggering long-lasting changes in synapses. NMDA receptor-dependent synaptic plasticity plays roles not only in physiological functions such as learning and memory, but also in unwanted pathological conditions such as chronic pain. This review addresses recent progress on NMDA receptors in neuropathic pain, with particular emphasis on the NR2B-subunit-containing receptors. The expression and function of NMDA receptors in synaptic plasticity in the pain transmission pathway from dorsal root ganglia to the anterior cingulate cortex is reviewed, and preclinical and clinical investigations of selective NMDA receptor in neuropathic pain are discussed. The NMDA receptors, in particular NR2B-containing NMDA receptors, serve as promising targets for treatment of neuropathic pain.
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PMID:Targeting the NMDA receptor subunit NR2B for the treatment of neuropathic pain. 1978 73

Acute nociceptive pain is an undesirable feeling but has a physiological significance as a warning system for living organisms. Conversely, chronic pain is lacking physiological significance, but rather represents a confusion of nerve functions. The neuropathic pain that occurs after peripheral nerve injury (PNI) is perhaps the most important type of chronic pain because it is refractory to available medications and thus remains a heavy clinical burden. In recent decades, studies have shown that spinal microglia play a principal role in the alterations in synaptic functions evoking this pain. It is also clear that the P2X4 receptor (P2X4R), a subtype of ionotropic ATP receptors, is upregulated exclusively in spinal microglia after PNI and plays a key role in evoking neuropathic pain. Neuropathic pain is caused by several conditions associated with activated microglia without nerve damage. 'Microgliopathic pain' is a new concept indicating such abnormal pain related to activated microglia.
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PMID:A state-of-the-art perspective on microgliopathic pain. 3048

Neuropathic pain is the most important type of chronic pain because it is refractory to available medications. Neuropathic pain occurs after peripheral nerve injury (PNI) or nerve damage by various reasons. In recent decades, a growing body of evidence shows that spinal microglia and P2X4 receptor (P2X4R), a subtype of ionotropic ATP receptors, play a principal role in evoking this pain. Understanding the functions of microglial P2X4R in evoking this pain provides potential strategies for developing new treatments for neuropathic pain.
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PMID:Role of the P2X4 receptor in neuropathic pain. 3087