Reversal of behavioural and electrophysiological correlates of experimental peripheral neuropathy by the NK 1 receptor antagonist GR205171 in rats

Abstract

In adult rats response latencies to innocuous mechanical stimuli were found to be reduced and, in electrophysiological studies, the receptive fields of dorsal horn neurones were enlarged 7–14 days after chronic constriction injury of the sciatic nerve. The NK 1 receptor antagonist GR205171 at 3 mg kg −1 blocked responses to NK 1 agonist evoked activity and reversed the mechanical hypersensitivity following nerve ligation in behavioural assays. GR205171 also reversed the receptive field expansion of spinal dorsal horn neurones caused by loose ligation of the sciatic nerve in an electrophysiological assay in anaesthetised rats. The less active enantiomer L-796,325 did not block NK 1 agonist evoked activity at up to 10 mg kg −1 and had no effect on behavioural or electrophysiological changes following nerve injury, indicating that the effects of GR205171 were attributable to selective NK 1 receptor blockade. These data suggest that NK 1 receptor antagonists may be useful for the treatment of certain types of neuropathic pain.