Gabapentin reduces allodynia and hyperalgesia in painful diabetic neuropathy rats by decreasing expression level of Nav1.7 and p-ERK1/2 in DRG neurons.

It has been confirmed that gabapentin (GBP) induced a inhibition of the voltage-gated persistent sodium current in chronically compressed dorsal root ganglion (DRG) neurons. The persistent sodium current is found in excitable DRG neurons of painful diabetic neuropathy (PDN) rats where it is mediated by tetrodotoxin (TTX) sensitive sodium channels. Recently, many groups have used models of neurological disorder to explore the mechanism of GBP in neuropathic pain. There is no evidence, however, to explain the particular mechanism of GBP, including its analgesic actions in PDN rats. These issues were addressed in the present study. Using behavioral testing, we found that diabetes leads to mechanical allodynia and thermal hyperalgesia and these effects were reversed by a continuous GBP injection. To investigate the mechanism of GBP's reduction in neural excitability, we systematically analyzed the expression of Nav1.7 and p-ERK1/2 and tested the effect of GBP on these proteins. Diabetes significantly increased the excitability of DRG neurons and the expression of Nav1.7 and p-ERK1/2, and GBP significantly inhibited these changes. These results suggest that the inhibitory effect of GBP on the expression of Nav1.7 and p-ERK1/2 might be one of the analgesic mechanisms of action of GBP. This may partially explain the antinociceptive action of GBP in the PDN rats.