HALOTHANE ENHANCES SUPPRESSION OF SPINAL SENSITIZATION BY INTRATHECALMORPHINE IN THE RAT FORMALIN TEST

Background: Injection of formalin in the hindpaw of the rat induces in tense C-fiber activity accompanied by brief flinching of the injected paw (phase 1) and gives rise to facilitated spinal processing characte rized by renewed flinching beginning 15 min after injury and lasting 4 0 min or mote (phase 2). In previous work, isoflurane, administered du ring phase 1, slightly reduced phase-2 activity, whereas the addition of intrathecal morphine dramatically inhibited phase 2, even with nalo xone reversal 6 min after the formalin injection. We used a similar mo del to determine whether intrathecal morphine could block spinal sensi tization in the absence of inhalation anesthetic. Methods: Hot plate t ests at 52 degrees C and radiant heat-evoked hindpaw withdrawal tests were used to determine optimal doses of agonists and antagonists. The formalin test was carried out on male Sprague-Dawley rats, which were divided into five groups. A combination of naloxone 0.5 mg/kg and nalt rexone 0.5 mg/kg was administered subcutaneously 6 min after the forma lin injection to all animals except controls (group 1) to prevent ongo ing opioid effect. Groups 1-3 received intrathecal saline, and groups 4 and 5 received intrathecal morphine 30 mu g 20 min before formalin i njection. Halothane was administered for 1-2 min to facilitate formali n injection for groups 1, 2, and 4. In groups 3 and 5 halothane was ad ministered from 5 min before tee 6 min after formalin injection. The n umber of flinches per minute was counted 1 and 5 min after formalin ad ministration and thereafter at 5-min intervals for 1 h. The total numb er of flinches at 1 and 5 min was considered as phase-1 activity, and the total number of flinches during the 10-60-min interval was conside red as phase 2. Results: Phase-2 activity for groups 1 and 2 was nearl y identical, demonstrating no appreciable effect of the opioid antagon ists alone. Groups 3 (halothane alone) and 4 (morphine alone) exhibite d a significant decrease in phase-2 activity. Group 5 (morphine plus h alothane) demonstrated a profound decrease in phase-2 activity, which was significantly more profound than that of groups 3 or 4. Conclusion s Intrathecal morphine, administered before formalin injection but ant agonized before the onset of phase 2 of the formalin test, significant ly suppresses sensitization of dorsal horn neurons. This suppression i s significantly increased by coadministration of halothane anesthesia.