SELECTIVE NEUROKININ-1 RECEPTOR ANTAGONISTS ARE ANTI-HYPERALGESIC IN A MODEL OF NEUROPATHIC PAIN IN THE GUINEA-PIG

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) ha s aided in our understanding of the pathology and pharmacology of neur opathic pain. This report is the first clear demonstration using selec tive neurokinin-1 receptor antagonists of a potentially novel therapeu tic approach to the treatment of neuropathic pain resulting from perip heral nerve damage in a guinea-pig model.(19) The neurokinin-1 recepto r antagonists, SDZ NKT 343(11,26,27) and LY 303,870(8) significantly r educed mechanical hyperalgesia following oral and intrathecal administ ration, (R,R)-SDZ NK T343, the enantiomer of SDZ NKT 343 did not show anti-hyperalgesic activity. RPR 100,893(6) showed significant anti-hyp eralgesic activity only following intrathecal administration suggestin g poor absorption or ion level penetration of the blood-brain barrier. These results imply that neurokinin-1 receptor antagonists offer a ne w class of anti-hyperalgesic drugs with a largely central site of acti on in neuropathic pain. (C) 1998 IBRO, Published by Elsevier Science L td.