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Implications and mechanism of action of gabapentin in neuropathic pain
Ankesh Kukkar,Anjana Bali,Nirmal Singh,Amteshwar Singh Jaggi 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.3
Gabapentin is an anti-epileptic agent but now itis also recommended as first line agent in neuropathic pain,particularly in diabetic neuropathy and post herpetic neuralgia. a2d-1, an auxillary subunit of voltage gated calciumchannels, has been documented as its main target and itsspecific binding to this subunit is described to producedifferent actions responsible for pain attenuation. Thebinding to a2d-1 subunits inhibits nerve injury-inducedtrafficking of a1 pore forming units of calcium channels(particularly N-type) from cytoplasm to plasma membrane(membrane trafficking) of pre-synaptic terminals of dorsalroot ganglion (DRG) neurons and dorsal horn neurons. Furthermore, the axoplasmic transport of a2d-1 subunitsfrom DRG to dorsal horns neurons in the form of anterogradetrafficking is also inhibited in response to gabapentinadministration. Gabapentin has also been shown to inducemodulate other targets including transient receptor potentialchannels, NMDA receptors, protein kinase C andinflammatory cytokines. It may also act on supra-spinalregion to stimulate noradrenaline mediated descendinginhibition, which contributes to its anti-hypersensitivityaction in neuropathic pain.
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