Antagonism of stimulation-produced antinociception from ventrolateral pontine sites by intrathecal administration of alpha-adrenergic antagonists and naloxone.
Focal electrical stimulation of the ventrolateral pontine tegmentum in conscious rats induced antinociception in approximately one-half of the animals screened, as indicated by a marked suppression of the thermally evoked tail-flick flexion reflex. The effectiveness of ventrolateral pontine stimulation in elevating tail-flick latency was significantly reduced by intrathecal microinjection of 30 micrograms of the non-selective alpha-adrenergic antagonist phentolamine, and was largely abolished by a 60-micrograms dose of this drug. The blockade of ventrolateral pontine stimulation-produced antinociception by phentolamine was maximal by 15 min postinjection, and was still evident 60 min after drug microinjection. Ventrolateral pontine stimulation-produced antinociception was also attenuated by intrathecal administration of the alpha 2-selective antagonist yohimbine (37 micrograms) and the opioid antagonist naloxone (30 micrograms), but not the alpha 1 antagonist WB-4101 (37 micrograms), the beta-adrenergic antagonist propranolol (111.6 micrograms) nor the serotonergic antagonist methysergide (30 micrograms). However, the antagonism of pontine stimulation-produced antinociception by naloxone was unlike that of phentolamine and yohimbine, in that it developed slowly and was only evident at 60 min postinjection. Hence naloxone's site of action may be distant from the injection site. These data indicate that the thermal antinociception produced by stimulation of the ventrolateral pons is mediated through spinal alpha 2-receptors and opioid receptors of uncertain location. The close proximity of many of the effective electrode placements to the rostral A5 and ventral subcoerulear A7 noradrenergic cell groups suggests that noradrenergic spinopetal projections arising from these groups are involved in mediating the antinociception induced by stimulating these sites.
Miller
J F
JF
Department of Pharmacology, University of Illinois, Chicago 60680.
Proudfit
H K
HK
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000032:analysis; D004558:Electric Stimulation; D005260:Female; D007278:Injections, Spinal; D008784:Methysergide / Q000494:pharmacology; D008845:Microinjections; D009270:Naloxone / Q000494:pharmacology*; D009474:Neurons / Q000201:enzymology; D010146:Pain / Q000503:physiopathology*; D010646:Phentolamine / Q000494:pharmacology; D011149:Pons / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D015016:Yohimbine; D009270:Naloxone; D011433:Propranolol; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D004299:Dopamine beta-Hydroxylase; D008784:Methysergide; D010646:Phentolamine