dextrorphan and Peripheral-Nervous-System-Diseases

Rats with an experimental painful peripheral neuropathy (the CCI model) display heat-hyperalgesia and mechanoallodynia. Previous work has shown that the heat-hyperalgesia is suppressed by dextrorphan (DEX) and other N-methyl-D-aspartate (NMDA) receptor antagonists. The present work shows that when tested in the same rats, a dose of DEX that is maximally effective against heat-hyperalgesia has no effect on mechano-allodynia. The results suggest that different kinds of abnormal pain sensations may be caused by different pathophysiologic mechanisms that may respond differently to drug therapy.

Topics: Animals; Dextrorphan; Hot Temperature; Hyperalgesia; Male; Pain; Peripheral Nervous System Diseases; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Sciatic Nerve

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.

Topics: Animals; Behavior, Animal; Dextrorphan; Injections, Spinal; Ketamine; Male; Pain; Pain Measurement; Peripheral Nervous System Diseases; Rats; Rats, Sprague-Dawley; Sciatic Nerve

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.

Topics: Animals; Dextrorphan; Dose-Response Relationship, Drug; Hot Temperature; Injections, Intraperitoneal; Injections, Spinal; Pain; Pain Threshold; Peripheral Nervous System Diseases; Rats; Reaction Time; Sciatic Nerve