We have tested for anti-nociceptive effects of the
anticonvulsant KCNQ channel opener, N-(2-amino-4-(4-fluorobenzylamino)-phenyl)carbamic
acid ethyl
ester (
retigabine), in rat models of experimental
pain. In the chronic constriction injury and spared nerve models of
neuropathic pain, injection of
retigabine (5 and 20 mg/kg, p.o.) significantly attenuated (P<0.05) mechanical
hypersensitivity in response to pin prick stimulation of the injured hindpaw. In contrast,
retigabine had no effect on mechanical
hypersensitivity to von Frey stimulation of the injured hindpaw in either model. Cold sensitivity in response to
ethyl chloride was only attenuated (P<0.05) in the chronic constriction injury model. In the
formalin test,
retigabine (20 mg/kg, p.o.) attenuated flinching behaviour in the second phase compared with vehicle (P<0.05), and this effect was completely reversed by the KCNQ channel blocker
10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone (XE-991; 3 mg/kg, i.p.). Neither
retigabine nor
XE-991 administration affected the latency to respond to noxious thermal stimulation of the tail in control animals. These results suggest that
retigabine may prove to be effective in the treatment of
neuropathic pain.