Increase in 5-HT synthesis in the dorsal part of the spinal cord, induced by a nociceptive stimulus: blockade by morphine.

The effects of a nociceptive peripheral stimulus and/or morphine upon endogenous tryptophan levels (TRP), specific activity of tryptophan (S.A. of TRP) and serotonin (5-HT) synthesis in the dorsal and ventral spinal cord, the brainstem and the forebrain were investigated in anaesthetized rats. Whereas endogenous TRP and S.A. of TRP were not found to be affected by any of the manipulations described below, 5-HT synthesis was markedly altered. The application of a prolonged and intense nociceptive electrical stimulus to the tail induced a rise in 5-HT synthesis which was dependent on the part of the CNS considered, with the dorsal cord being the most sensitive (25%), the ventral cord and the brainstem being effected to a lesser extent (14% and 16% respectively), and the forebrain not being affected significantly. By contrast, the application of a prolonged and innocuous electrical stimulus on the tail was not followed by any detectable changes in 5-HT synthesis. Morphine administration (1 mg/kg; i.v.) did not significantly alter 5-HT synthesis in the four CNS regions considered. Nevertheless, the same morphine dose did induce a highly significant (P less than 0.005) reduction in the increase in 5-HT synthesis induced by the nociceptive stimulus, both in the dorsal cord and in the brainstem. Such an effect was not seen in the ventral cord. The specificity of these morphine effects was demonstrated by their naloxone reversibility; on the other hand, naloxone alone failed to modify the stimulus-induced increase in 5-HT synthesis seen in the dorsal cord and the brainstem. The results, particularly those concerning the dorsal cord, are discussed with reference to pain mechanisms and morphine analgesia. They suggest that peripheral nociceptive messages induce an increased activity in some bulbo-spinal 5-HT pathways and that a low dose of morphine can counteract such an effect. It is proposed that exogenous opiates exert a complex regulation of bulbo-spinal 5-HT pathways. Functional significances of these processes are discussed.