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)

Different pathophysiological mechanisms are thought to operate in chronic sciatica. Nociceptive and neuropathic pain components can be distinguished. Neuropathic pain may be caused by lesions of nociceptive sprouts within the degenerated disc (local neuropathic), mechanical compression of the nerve root (mechanical neuropathic root pain), or by action of inflammatory mediators (inflammatory neuropathic root pain) originating from the degenerative disc even without any mechanical compression. Since different pain-generating mechanisms possibly underlie sciatic pain, the term mixed pain syndrome was established. The incidence of each pain component in chronic sciatica as well as validated diagnostic tools to identify them remain unknown. Current analgesic therapeutic first-line strategies for chronic sciatica rely on NSAIDs that are known to relieve nociceptive pain only. In neuropathic pain, different therapeutic approaches are effective, i.e., antidepressants such as amitriptyline and anticonvulsants such as gabapentin, carbamazepine, and pregabalin. Therefore, the combination of these analgesic compounds with NSAID could be useful in patients with sciatic pain who do not respond to NSAID.
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PMID:[How neuropathic is sciatica? The mixed pain concept]. 1506 5

Neuropathic pain is characterized by central sensitization. The interaction between N-methyl-D-aspartate receptors (NMDARs) and postsynaptic density protein-95 (PSD-95) plays a major role in central sensitization. Here, we aimed to investigate the analgesic effect of disruption of the interaction between NMDAR and PSD-95. Chronic dorsal root ganglia compression model rats were used to mimic sciatica. Thermal hyperalgesia and mechanical allodynia were evaluated. The expression of spinal phospho-NR2B, PSD-95, calcium/calmodulin-dependent protein kinase II (CaMKII), and cAMP response element binding protein (CREB) was measured using western blotting. A mimetic peptide Myr-NR2B9c was injected intrathecally to disrupt the interaction between PSD-95 and NR2B and detected by coimmunoprecipitation. Chronic dorsal root ganglia compression surgery induced thermal hyperalgesia and mechanical allodynia, and upregulated pain-related proteins such as phospho-NR2B, PSD-95, CaMKII, and CREB expressions in the spinal cord. Myr-NR2B9c disrupted the interaction between NR2B-containing NMDARs and PSD-95 in the spinal cord. Intrathecal administration of Myr-NR2B9c attenuated neuropathic pain behaviors and downregulated the expressions of phospho-NR2B, PSD-95, CaMKII, and CREB in the spinal cord. The present study indicates that dissociation of NR2B-containing NMDARs from PSD-95 inactivates CaMKII and CREB signaling and relieves pain.
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PMID:Perturbing NR2B-PSD-95 interaction relieves neuropathic pain by inactivating CaMKII-CREB signaling. 2874 67