Role of 5-HT and NA in spinal dopaminergic analgesia

Spinal rats and rats with an intact neuraxis given the dopamine (DA) agonist R-apomorphine (0.31-1.75 mumol/kg) in the lumbar subarachnoid space by intrathecal injection were tested 5 and 10 min later for spinal analgesia (increased tail-flick response latency). Apomorphine produced analgesia in spinal rats but not in rats with an intact neuraxis. However, pretreatment of intact rats with the serotonergic (5-HT) receptor antagonist methysergide, the noradrenergic (NA) receptor antagonist phentolamine or the two antagonists together led to a dose-dependent analgesia following apomorphine. Intact rats pretreated with the monoamine depleting drug reserpine, the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA) or the NA synthesis inhibitor FLA 63 also showed analgesia to apomorphine. On the other hand, pretreatment with the catecholamine depleting agent alpha-methyl-p-tyrosine (AMPT), the beta-adrenergic receptor blocker propranolol or the opioid receptor antagonist naloxone failed to produce DA analgesia. The present findings suggest that both 5-HT and NA descending fiber systems exert tonic inhibitory effects on spinal DA nociceptive processes.