Intrathecal treatment with dextrorphan or ketamine potently reduces pain-related behaviors in a rat model of peripheral mononeuropathy.
The therapeutic effects of dextrorphan and ketamine, two non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, on neuropathic pain-related behaviors were examined in rats with peripheral mononeuropathy induced by loose ligation of the common sciatic nerve (chronic constrictive injury, CCI). Four daily intrathecal treatments (beginning 1 h after nerve ligation) with dextrorphan or ketamine (12.5-100 nmol) reliably attenuated hyperalgesia to radiant heat and spontaneous pain-related behaviors in CCI rats. Thermal hyperalgesia also was reduced in CCI rats receiving a single intrathecal treatment with either dextrorphan or ketamine (50 and 100 nmol for each compound) on day 3 after nerve ligation when thermal hyperalgesia was well developed. Since both dextrorphan and ketamine are currently utilized in other clinical applications, the results suggest a new therapeutic utility of these 'old' compounds in treatment of neuropathic pain syndromes resulting from peripheral nerve injury.
Department of Anesthesiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
J
J
Mao
D D
DD
Price
R L
RL
Hayes
J
J
Lu
D J
DJ
Mayer
H
H
Frenk
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003917:Dextrorphan / Q000008:administration & dosage / Q000627:therapeutic use*; D007278:Injections, Spinal; D007649:Ketamine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000502:physiology
D003917:Dextrorphan; D007649:Ketamine