Antinociceptive action of carbamazepine on thermal hypersensitive pain at spinal level in a rat model of adjuvant-induced chronic inflammation.
OBJECTIVE
Systemic carbamazepine, a voltage-gated sodium channel blocker, has been reported to dose-dependently reduce inflammatory hyperalgesia. However, the antinociceptive effects of carbamazepine on the spinal cord in inflammatory conditions are unclear. The aim of the present study was to evaluate the antinociceptive effects of carbamazepine on the spinal cord in a chronic inflammatory condition.


METHODS
In Sprague-Dawley rats, a chronic inflammatory condition was induced by complete Freund's adjuvant (CFA) inoculation into the tail. Tail flick (TF) latencies were measured following intraperitoneal carbamazepine, or intrathecal carbamazepine or tetrodotoxin injection in intact rats and in the chronic inflammatory rats. From the values of TF latency at 60 min after drug injection, the effective dose required to produce 50% response (ED(50)) of each drug was derived.


RESULTS
Carbamazepine attenuated thermal responses with both systemic and intrathecal administration. The effect was more evident in rats with chronic inflammation than in intact rats; the ED(50s) of intraperitoneal carbamazepine in intact and inflamed rats were 12.39 and 1.54 mg/kg, and those of intrathecal carbamazepine were 0.311 and 0.048 nmol, respectively. Intrathecal tetrodotoxin also clearly inhibited the response, with ED(50s) of 1.006 pmol in intact rats and 0.310 pmol in inflamed rats. The relative potencies of intrathecal carbamazepine versus tetrodotoxin for inhibition were approximately 1:150-1:300 in intact and inflamed rats.


CONCLUSIONS
These results indicate that the inhibition of voltage-gated sodium channels, at least tetrodotoxin-sensitive channels, may contribute to the antinociceptive effect of carbamazepine on CFA-induced inflammatory pain, since lower doses of intrathecal carbamazepine and tetrodotoxin attenuated thermal responses to a greater extent in inflamed rats than in intact rats.
Department of Anesthesiology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka 589-8511, Japan.
Tatsushige
T
Iwamoto
Yoshihiro
Y
Takasugi
Hideaki
H
Higashino
Hiroyuki
H
Ito
Yoshihisa
Y
Koga
Shinichi
S
Nakao
D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001169:Arthritis, Experimental / Q000150:complications* / Q000188:drug therapy; D002220:Carbamazepine / Q000008:administration & dosage / Q000494:pharmacology*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005620:Freund's Adjuvant; D006987:Hypesthesia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013131:Spine / Q000187:drug effects*; D013623:Tail / Q000473:pathology; D013779:Tetrodotoxin / Q000008:administration & dosage / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D000779:Anesthetics, Local; D026941:Sodium Channel Blockers; D002220:Carbamazepine; D013779:Tetrodotoxin; D005620:Freund's Adjuvant