Visceral antinociceptive effects of spinal clonidine combined with morphine, [D-Pen2, D-Pen5] enkephalin, or U50,488H.
BACKGROUND
Visceral pain is an important component of many clinical pain states. The perispinal administration of drug combinations rather than a single agent may reduce side effects while maximizing analgesic effectiveness. The purpose of this study was to examine the nature of interactions between an alpha 2-adrenergic agonist (clonidine) and a mu-opioid agonist (morphine), a delta-opioid agonist ([D-Pen2, D-Pen5] enkephalin [DPDPE]), or a kappa-opioid agonist (U50,488H).


METHODS
Colorectal distension was used to elicit a nociceptive visceromotor response (contraction of abdominal musculature) in rats. The ability of intrathecally administered clonidine alone or in combination with morphine, DPDPE, or U50,488H to alter thresholds for the production of the visceromotor response was examined.


RESULTS
Clonidine produced dose-dependent reduction in threshold. U50,488H, at the doses tested, showed no synergistic interaction with clonidine.


CONCLUSIONS
Spinal combinations of alpha 2-adrenergic and mu- or delta- but not kappa-opioid agonists may be beneficial in the control of visceral pain.
Harada
Y
Y
Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Nishioka
K
K
Kitahata
L M
LM
Kishikawa
K
K
Collins
J G
JG
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D003106:Colon / Q000502:physiology; D004357:Drug Synergism; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D010146:Pain / Q000188:drug therapy*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000502:physiology
D000700:Analgesics; D004745:Enkephalins; D011759:Pyrrolidines; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; D003000:Clonidine