DIFFERENT ROLES OF ALPHA(2)-ADRENOCEPTORS OF THE MEDULLA VERSUS THE SPINAL-CORD IN MODULATION OF MUSTARD OIL-INDUCED CENTRAL HYPERALGESIA IN RATS

We attempted to determine the roles of spinal versus medullary alpha(2 )-adrenoceptors in modulation of central hyperalgesia in rats. Central hyperalgesia was produced by applying mustard oil (50%) to the skin o f the ankle of one hindpaw. The threshold for eliciting a hindlimb fle xion reflex was determined by applying a series of calibrated monofila ments to the glabrous skin of the hindpaw contralaterally(= control) o r ipsilaterally to the mustard oil-treated ankle (= outside the area o f primary hyperalgesia). Medetomidine (an alpha(2)-adrenoceptor agonis t; 1 mu g), atipamezole (an alpha(2)-adrenoceptor antagonist; 2.5 mu g ) or saline was microinjected into the lateral reticular nucleus of th e medulla, the nucleus raphe magnus, or intrathecally to the lumbar sp inal cord 12 min before the mustard oil treatment. Following saline in jections, mustard oil produced a significant decrease of the hindlimb withdrawal threshold in the mustard oil-treated limb but not in the co ntralateral limb. Atipamezole in the lateral reticular nucleus produce d a complete reversal of the hyperalgesia but no effect on the thresho ld of the intact limb. However, atipamezole in the raphe magnus nucleu s or in the lumbar spinal cord did not produce a significant attenuati on of the hyperalgesia. Medetomidine in the spinal cord, but not in th e lateral reticular nucleus, reversed the hyperalgesia. At this dose r ange (up to 3 mu g), medetomidine in the spinal cord of nonhyperalgesi c control rats did not produce any significant change in the withdrawa l response of hindlimbs or in the tail-flick latency. The results indi cate that neurogenic inflammation induces significant plastic changes in the function of alpha(2)-adrenergic pain regulatory mechanisms. In rats with mustard oil-induced central hyperalgesia, an alpha(2)-adreno ceptor antagonist produces an antihyperalgesic effect due to an action on the caudal ventrolateral medulla, whereas an alpha(2)-adrenoceptor agonist produces an enhanced antinociceptive effect due to a direct a ction on the spinal cord.