ALPHA-2-ADRENOCEPTORS INHIBIT A NOCICEPTIVE RESPONSE IN NEONATAL RAT SPINAL-CORD

alpha-2-Adrenoceptors mediate analgesia in vivo. The present study explored the actions of the alpha-2-adrenoceptor agonists dexmedetomidine and clonidine on a nociceptive response in isolated neonatal rat spinal cord. Stimulation of a dorsal root generates a slow ventral root potential (slow VRP) at the corresponding ipsilateral ventral root. The slow VRP meets several criteria for a nociceptive response. Dexmedetomidine (10 nM) and clonidine (200 nM) depressed the slow VRP by approximately 80%. Dexmedetomidine's action was approximately linear over the concentration range 0.5-500 nM, whereas clonidine (20 nM-5-mu-M) exerted biphasic effects. The profile of agonist and antagonist effectiveness characterized the receptor(s) as alpha-2-adrenoceptors; the subtype could not be identified as either alpha-2A or alpha-2B. Naloxone pretreatment partially blocked dexmedetomidine's effect, suggesting a possible endogenous opiate involvement. Dexmedetomidine (0.5-2.0 nM) also depressed the VRP evoked by application of substance P to the cord, implicating postsynaptic as well as possible presynaptic actions. At high concentrations, dexmedetomidine (50-500 nM) depressed the monosynaptic reflex, probably through non-alpha-2-receptor(s). Results from the neonatal spinal cord correlate well with those from in vivo analgesia studies. They suggest an important direct spinal contribution to alpha-2-adrenoceptor-mediated analgesia.