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.
D000818:Animals; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009619:Nociceptors / Q000187:drug effects; D009638:Norepinephrine / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine