title: Contrasting actions of intrathecal U50,488H, morphine, or [D-Pen2, D-Pen5] enkephalin or intravenous U50,488H on the visceromotor response to colorectal distension in the rat.
abstract: BACKGROUND
  Visceral sensations are an important component of many clinical pain states. It is apparent that intrathecal pain relief may be more effective if appropriate combinations of drugs rather than a single agent can be used. The purpose of this study was to examine the relative contribution of opioid receptor subtypes to visceral antinociception using colorectal distension as a visceral pain model.
  
  
  METHODS
  The minimum colorectal distending pressure necessary to evoke a visceromotor response (contraction of abdominal musculature) was determined before and after the administration of opioid agonists for the mu (morphine), delta ([D-Pen2, D-Pen5] enkephalin [DPDPE]), and kappa (U50,488H) opioid receptors. In addition to the three drugs administered intrathecally, U50, 488H was also administered intravenously.
  
  
  RESULTS
  Morphine and DPDPE produced a reversible increase in threshold for activation of the visceromotor response (50% maximum possible effect [MPE] at intrathecal doses of 2.2 and 16.4 micrograms, respectively). The maximum intrathecal dose of U50,488H (100 micrograms) produced only a 20% MPE. Intravenous U50,488H produced a 50% MPE at a dose of 2.6 mg/kg.
  
  
  CONCLUSIONS
  The results suggest that spinal mu- and delta- but not kappa-opioid receptors have a significant role in the modulation of visceral nociception induced by colorectal distension. In addition, the results indicate that activation of nonspinal kappa receptors may mediate visceral antinociception.
authors.affiliation: Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Harada
authors.forename: K
authors.initials: K
authors.lastname: Nishioka
authors.forename: L M
authors.initials: LM
authors.lastname: Kitahata
authors.forename: K
authors.initials: K
authors.lastname: Nakatani
authors.forename: J G
authors.initials: JG
authors.lastname: Collins
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003106:Colon / Q000502:physiology; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy*; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000502:physiology
chemical_list: 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)-