Antinociceptive effects of carbachol microinjected into different portions of the mesencephalic periaqueductal gray matter of the rat.
The changes in tail-flick latency (TFL) to noxious heating of the skin produced by the microinjection of carbachol (CCh) into the dorsal (dPAG), lateral (lPAG), and ventral (vPAG) portions of the mesencephalic periaqueductal gray matter (PAG) were studied in the rat. A significant increase in TFL was produced by CCh (0.2 microgram/0.5 microliter) microinjected into sites widely distributed within the PAG. The effect of CCh was stronger in the most caudal portion of the DPAG. Smaller effects were obtained after injection of CCh into the aqueduct, indicating that drug diffusion from the injection sites to the aqueduct lumen is unlikely to cause the antinociceptive effect of CCh. Dimethyl-phenyl-piperazinium (0.35 microgram/0.5 microliter), but not bethanechol (0.22 and 0.44 microgram/0.5 microliter), produced effects similar to CCh (0.2 microgram/0.5 microliter), when injected into the dPAG. The effects of CCh were inhibited by the previous administration of mecamylamine (1 microgram/0.5 microliter), but not atropine (1 microgram/0.5 microliter) or naloxone (1 microgram/0.5 microliter), into the dPAG. These results are indicative that antinociception produced by CCh from the dPAG depends on nicotinic, but not muscarinic or opioid mechanisms within the dPAG. The intraperitoneal administration of phenoxybenzamine (1 mg/kg) or mecamylamine (1 mg/kg), but not naloxone (1 mg/kg), methysergide (1 mg/kg), or atropine (1 mg/kg), inhibited the effects of CCh injected into the dPAG. In contrast, a higher dose of intraperitoneal phenoxybenzamine (5 mg/kg) was ineffective against the antinociception evoked by CCh when injected into the vPAG. Therefore, the effects of CCh from the dPAG may depend on the activation of centrifugal pathways involving both nicotinic and alpha-adrenergic mechanisms. In addition, the results indicate that different cholinergic substrates in the PAG may mediate both alpha-adrenergic and non-alpha-adrenergic descending pain mechanisms activated by the dPAG and vPAG, respectively.
Guimarães
A P
AP
Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Prado
W A
WA
D000700:Analgesics / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D001931:Brain Mapping; D002217:Carbachol / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D008636:Mesencephalon / Q000033:anatomy & histology / Q000502:physiology*; D008784:Methysergide / Q000494:pharmacology; D008845:Microinjections; D009270:Naloxone / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D010487:Periaqueductal Gray / Q000033:anatomy & histology / Q000502:physiology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012881:Skin Temperature / Q000187:drug effects
D000700:Analgesics; D018723:Bethanechol; D010643:Phenoxybenzamine; D009270:Naloxone; D004246:Dimethylphenylpiperazinium Iodide; D002217:Carbachol; D008784:Methysergide