Roles of monoaminergic, glycinergic and GABAergic inhibitory systems in the spinal cord in rats with peripheral mononeuropathy.

The current study was designed to determine if the monoaminergic descending inhibitory system and the glycinergic and GABAergic inhibitory systems were activated in the spinal cord in the presence of peripheral mononeuropathy produced by loose ligatures around the common sciatic nerve. The time course of withdrawal latencies to thermal stimuli were assayed in lesioned and sham-operated rats. The levels of monoamines (serotonin; 5-HT, noradrenaline, and dopamine), glycine and gamma-aminobutyric acid (GABA) in the dorsal half of the spinal cord were measured using HPLC with electrochemical detection. Furthermore, on day 7 after nerve ligation, intrathecal methysergide, yohimbine, strychnine or bicuculline was administered in order to investigate the roles of these inhibitory neuromodulators in this pathological pain state. The levels of 5-HT and noradrenaline significantly increased in both ipsi- and contralateral sides of the dorsal half of the lumbar spinal cord in the lesioned, but not sham-operated animals. The levels of glycine and GABA in the ipsilateral dorsal half of the spinal cord increased significantly and were significantly higher than in the contralateral side. Intrathecal antagonists of 5-HT, noradrenaline, glycine and GABA produced enhancement of the magnitude of hyperalgesia on the lesioned hindpaw. We also examined the effects of four daily single treatments with intrathecal MK-801 beginning 15 min prior to nerve ligation on the development of thermal hyperalgesia and on the contents of the neuromodulators in the ligation model. MK-801 treatment effectively abolished the increases in 5-HT, noradrenaline, glycine and GABA levels as well as preventing the development of hyperalgesia. The results of the present study suggest that the pathological pain state activates or increases the activity of these inhibitory systems.