Dextrorphan relieves neuropathic heat-evoked hyperalgesia in the rat.
Dextrorphan (DEX), a non-competitive NMDA receptor antagonist, was given intraperitoneally and intrathecally (i.t.) to rats with an experimental painful peripheral mononeuropathy. The neuropathy was created by placing loosely constrictive ligatures around the sciatic nerve, and the pain threshold was studied with the paw-flick method. The effects of DEX on the neuropathic heat-evoked hyperalgesia that follows this nerve injury were determined during the period of peak symptom severity. DEX given i.p. relieved heat-evoked hyperalgesia in a dose-dependent manner without producing motor impairment. The highest doses tested (12.5 and 25 mg/kg) produced a large but incomplete block (about 50%). DEX had no effect on the responsiveness of the paw on the control side. i.t. injection of 20 micrograms DEX completely blocked heat-hyperalgesia when tested 1 h later; again, the effect was achieved without motor impairment and without any change on the control side. These results suggest that DEX may be useful in the treatment of human neuropathic pain.
Tal
M
M
Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
Bennett
G J
GJ
D000818:Animals; D003917:Dextrorphan / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D010146:Pain / Q000188:drug therapy*; D017288:Pain Threshold / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D012584:Sciatic Nerve / Q000502:physiology
D003917:Dextrorphan