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 microM) 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.
Department of Anesthesia, Stanford University School of Medicine, CA 94305-5123.
J J
JJ
Kendig
M K
MK
Savola
S J
SJ
Woodley
M
M
Maze
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000698:Analgesia; D000818:Animals; D000831:Animals, Newborn; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D020926:Medetomidine; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012023:Reflex, Monosynaptic / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; D009270:Naloxone; D003000:Clonidine; D020926:Medetomidine