Selective neurokinin-1 receptor antagonists are anti-hyperalgesic in a model of neuropathic pain in the guinea-pig

Abstract

Neuropathic pain is poorly managed by conventional analgesic therapy, such as non-steroidal anti-inflammatory drugs and opiates. [1, 4, 7]The development of animal models of peripheral neural damage [3, 5, 10, 20]has aided in our understanding of the pathology and pharmacology of neuropathic pain. This report is the first clear demonstration using selective neurokinin-1 receptor antagonists of a potentially novel therapeutic approach to the treatment of neuropathic pain resulting from peripheral nerve damage in a guinea-pig model. [19]The neurokinin-1 receptor antagonists, SDZ NKT 343 [11, 26, 27]and LY 303,870 [8]significantly reduced mechanical hyperalgesia following oral and intrathecal administration. (R,R)-SDZ NK T343, the enantiomer of SDZ NKT 343 did not show anti-hyperalgesic activity. RPR 100,893 [6]showed significant anti-hyperalgesic activity only following intrathecal administration suggesting poor absorption or low level penetration of the blood–brain barrier. These results imply that neurokinin-1 receptor antagonists offer a new class of anti-hyperalgesic drugs with a largely central site of action in neuropathic pain.