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 phantom phenomena occur commonly after spinal cord injury (SCI) but their molecular basis is not yet fully understood. Recent findings demonstrate abnormal expression of the Nav1.3 Na(+) channel within second-order spinal cord dorsal horn neurons and third-order thalamic neurons along the pain pathway after SCI, and suggest that this change makes these neurons hyperexcitable so that they act as pain amplifiers and generators. Delineation of molecular changes that contribute to hyperexcitability of pain-signaling neurons might lead to identification of molecular targets that will be useful in the treatment of neuropathic pain after SCI and related nervous system injuries.
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PMID:Fire and phantoms after spinal cord injury: Na+ channels and central pain. 1649 54

Neuropathic pain remains one of the most challenging of all neurological diseases and presents a large unmet need for improved therapies. Many mechanistic details are still lacking, but greater knowledge of overlapping mechanisms and disease comorbidities has highlighted key areas for intervention. These include peripheral and central hyperexcitability. Among the molecular drivers are ion channels (Nav1.7, Nav1.8, Nav1.3, Cav2.2, and alpha2-delta subunits) whose expression is changed during neuropathic pain and their block shows therapeutic utility. Block of a number of ligand-gated channels [transient receptor potential (TRP)V1, TRPM8, and neuronal nicotinic receptors (NNRs)], important in neural sensitization, may also prove beneficial. Other approaches, such as the modulation of peripheral excitability via CB1 receptors, reduction of spinal excitability through block of glutamate receptors (metabotropic glutamate receptor 5 and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate), block of activated spinal neuroglial (CCR2 and P2X7), or increasing spinal inhibition by enhancing monoaminergic activity, all offer exciting opportunities currently being validated in the clinic. Finally of note is the emergence of biological approaches, for example, antibodies, siRNA, gene therapy, offering powerful therapeutic additions with which to redress the neurological disease imbalances causing neuropathic pain.
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PMID:Neuropathic pain: emerging treatments. 1851 41

Neuropathic pain may arise following peripheral nerve injury though the molecular mechanisms associated with this are unclear. We used proteomic profiling to examine changes in protein expression associated with the formation of hyper-excitable neuromas derived from rodent saphenous nerves. A two-dimensional difference gel electrophoresis (2D-DIGE) profiling strategy was employed to examine protein expression changes between developing neuromas and normal nerves in whole tissue lysates. We found around 200 proteins which displayed a >1.75-fold change in expression between neuroma and normal nerve and identified 55 of these proteins using mass spectrometry. We also used immunoblotting to examine the expression of low-abundance ion channels Nav1.3, Nav1.8 and calcium channel alpha2delta-1 subunit in this model, since they have previously been implicated in neuronal hyperexcitability associated with neuropathic pain. Finally, S35methionine in vitro labelling of neuroma and control samples was used to demonstrate local protein synthesis of neuron-specific genes. A number of cytoskeletal proteins, enzymes and proteins associated with oxidative stress were up-regulated in neuromas, whilst overall levels of voltage-gated ion channel proteins were unaffected. We conclude that altered mRNA levels reported in the somata of damaged DRG neurons do not necessarily reflect levels of altered proteins in hyper-excitable damaged nerve endings. An altered repertoire of protein expression, local protein synthesis and topological re-arrangements of ion channels may all play important roles in neuroma hyper-excitability.
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PMID:Proteomic profiling of neuromas reveals alterations in protein composition and local protein synthesis in hyper-excitable nerves. 1870 27