Abstract
Gabapentin, an antiepileptic drug, selectively interacts with alpha-2 / delta 1 calcium channel subunits (CACNA2D1), and has an analgesic effect on neuropathic pain. Neuropathic pain is known to be accompanied by the up-regulation of the expression of many genes. We observed the involvement of the analgesic effect of gabapentin and the alteration of the expression of genes in an inferior alveolar nerve-transected rat neuropathic pain model, in which IAN transection induced allodynia in whisker pads innervated by uninjured neurons.
We determined the up-regulation of the expression of several genes in the trigeminal ganglia of IAN-transected rats, including those for neuropeptides, GDNF receptor and CACNA2D1;however, these up-regulations were confined almost exclusively to injured neurons, and were not detected in the neurons innervating the allodynia area. Upon suppression of tactile allodynia in IAN-transected rats by intrathecal administration of gabapentin, the increased gene expression levels did not change, other than that of CACNA2D1, whose expression was reduced with the attenuation of allodynia.
These findings indicate that gabapentin relieves the allodynia developed in the cutaneous region innervated by uninjured neurons, but that the main target of gabapentin is the CACNA2D1 expressed in injured neurons.
