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Spinal mu and delta, but not kappa, opioid-receptor agonists attenuate responses to noxious colorectal distension in the rat. 1995

R M Danzebrink, and S A Green, and G F Gebhart
Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City, IA 52242 USA.

The antinociceptive efficacy of different opioid-receptor agonists following their intrathecal (i.t.) administration was examined in awake, unanesthetized rats in a model of visceral pain. Cumulative i.t. doses of the mu-preferring opioid-receptor agonist morphine produced dose-dependent attenuation of the change (increase) in mean arterial pressure (delta MAP) and elevation of the visceromotor threshold to colorectal distension (CRD). Similar dose-dependent antinociceptive effects were produced after i.t. administration of the mu opioid-receptor-selective agonist DAMPGO. Morphine and DAMPGO were equipotent against the delta MAP to phasic CRD (80 mm Hg, 20 sec), but DAMPGO was more than 6 times more potent than morphine in elevating the visceromotor threshold to an incrementing CRD. Intrathecal administration of the delta opioid-receptor-selective agonist DPDPE produced, like morphine and DAMPGO, a dose-dependent attenuation of the delta MAP to CRD; DPDPE was one-tenth as potent as morphine or DAMPGO. DPDPE also dose-dependently elevated the visceromotor threshold to CRD, but its efficacy was only half that of morphine or DAMPGO. The kappa opioid-receptor-selective agonist U 50488H was without antinociceptive efficacy after i.t. administration, but did attenuate responses to CRD after systemic administration. The antinociceptive effects produced by morphine and DAMPGO were antagonized by i.t. pretreatment with naloxone and the effects produced by DPDPE were antagonized by i.t. pretreatment with the delta opioid-receptor-selective antagonist naltrindole. These data indicate that local mu and delta, but not kappa, opioid receptors can modulate visceral nociceptive transmission in the spinal cord.

UI MeSH Term Description Entries
D007278 Injections, Spinal Introduction of therapeutic agents into the spinal region using a needle and syringe. Injections, Intraspinal,Injections, Intrathecal,Intraspinal Injections,Intrathecal Injections,Spinal Injections,Injection, Intraspinal,Injection, Intrathecal,Injection, Spinal,Intraspinal Injection,Intrathecal Injection,Spinal Injection
D008297 Male Males
D009020 Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D010146 Pain An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS. Suffering, Physical,Ache,Pain, Burning,Pain, Crushing,Pain, Migratory,Pain, Radiating,Pain, Splitting,Aches,Burning Pain,Burning Pains,Crushing Pain,Crushing Pains,Migratory Pain,Migratory Pains,Pains, Burning,Pains, Crushing,Pains, Migratory,Pains, Radiating,Pains, Splitting,Physical Suffering,Physical Sufferings,Radiating Pain,Radiating Pains,Splitting Pain,Splitting Pains,Sufferings, Physical
D011759 Pyrrolidines Compounds also known as tetrahydropyridines with general molecular formula (CH2)4NH. Tetrahydropyridine,Tetrahydropyridines
D012007 Rectum The distal segment of the LARGE INTESTINE, between the SIGMOID COLON and the ANAL CANAL. Rectums
D002404 Catheterization Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from INTUBATION in that the tube here is used to restore or maintain patency in obstructions. Cannulation,Cannulations,Catheterizations
D003106 Colon The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON. Appendix Epiploica,Taenia Coli,Omental Appendices,Omental Appendix,Appendices, Omental,Appendix, Omental
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004745 Enkephalins One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. Enkephalin

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