Spinal mu and delta, but not kappa, opioid-receptor agonists attenuate responses to noxious colorectal distension in the rat.
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.
Danzebrink
R M
RM
Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City, IA 52242 USA.
Green
S A
SA
Gebhart
G F
GF
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002404:Catheterization; D003106:Colon / Q000187:drug effects* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists*; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D012007:Rectum / Q000187:drug effects* / Q000503:physiopathology
D000700:Analgesics; D004745:Enkephalins; D011759:Pyrrolidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-