Effects of intracolonic opioid receptor agonists on polymodal pelvic nerve afferent fibers in the rat.
We studied the effects of intracolonic administration of opioid receptor agonists (ORAs) on responses of pelvic nerve afferent fibers to colorectal distension (CRD) and heat. Single-fiber recordings were made from the decentralized S1 dorsal rootlet in the rat. An approximately 7-cm length of descending colon was isolated in situ to permit intracolonic perfusion with Krebs solution, which, when the outflow was clamped, was used to distend the colon. Responses to noxious CRD (40 mmHg, 30 s) were tested after intracolonic instillation of mu-, delta- or kappa-ORAs. Intracolonic administration of the kappa-ORAs EMD 61,753 (n = 5/12) and U62,066 (n = 8/11), but not either the mu-ORA fentanyl or the delta-ORA SNC-80, concentration-dependently inhibited responses of afferent fibers. For fibers unaffected by intracolonic administration of EMD 61,753 or U62,066, intra-arterial administration of kappa-ORAs was effective. Forty-one of 54 mechanosensitive fibers also responded to intracolonic instillation of heated Krebs solution (50 degrees C). Intra-arterial injection of fentanyl or SNC-80 did not attenuate responses to heat. Either intracolonic or intra-arterial administration of EMD 61,753 or U62, 066, however, inhibited afferent fiber responses to heat. These results document that mechanical and thermal sensitivity of polymodal pelvic nerve afferent fibers innervating the rat colon can be inhibited peripherally by intracolonic instillation of kappa-ORAs.
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Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City, Iowa 52242, USA.
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Gebhart
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D000081:Acetamides / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D003106:Colon / Q000294:innervation*; D005283:Fentanyl / Q000494:pharmacology; D006358:Hot Temperature; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009412:Nerve Fibers / Q000737:chemistry / Q000502:physiology; D009475:Neurons, Afferent / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D010525:Peripheral Nerves / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation; D010879:Piperazines / Q000494:pharmacology; D011312:Pressure; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013126:Spinal Nerve Roots / Q000166:cytology
D000081:Acetamides; D000700:Analgesics; D000701:Analgesics, Opioid; D001549:Benzamides; D009292:Narcotic Antagonists; D010879:Piperazines; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D009270:Naloxone; C092095:asimadoline; C051272:spiradoline; D005283:Fentanyl