Decreased opioid-induced antinociception but unaltered G-protein activation in the genetic-diabetic NOD mouse

Eur J Pharmacol. 2000 Aug 11;401(3):375-9. doi: 10.1016/s0014-2999(00)00459-3.

Abstract

Previous evaluation of antinociceptive action in experimental diabetes has been conducted almost exclusively in chemically induced diabetes mellitus. The purpose of the present study was to evaluate antinociceptive response and G-protein activation by mu-opioid receptor and delta-opioid receptor agonists in the genetic non-obese diabetic (NOD) mouse, a model of type I insulin-dependent diabetes mellitus (IDDM). Tail-flick latency before and after hyperglycemia was unaltered. Hyperglycemic NOD mice were hyporesponsive to intracerebroventricular (i.c.v.) injections of [D-Ala(2)]deltorphin II but not to [D-Ala(2), N-MePhe(4), Gly-ol(5)]enkephalin (DAMGO); however, G-protein activation in pons/medulla assessed by [35S]GTPgammaS binding was not diminished. This suggests that a G-protein defect in signaling cannot account for the hyporesponsiveness of antinociception in this genetic model of IDDM.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Animals
  • Benzamides / pharmacology
  • Binding, Competitive / drug effects
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology*
  • Female
  • GTP-Binding Proteins / drug effects*
  • GTP-Binding Proteins / metabolism
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Injections, Intraventricular
  • Medulla Oblongata / drug effects
  • Medulla Oblongata / metabolism
  • Membranes / drug effects
  • Membranes / metabolism
  • Mice
  • Mice, Inbred NOD
  • Nociceptors / drug effects
  • Oligopeptides / pharmacology
  • Pain / prevention & control*
  • Piperazines / pharmacology
  • Pons / drug effects
  • Pons / metabolism
  • Receptors, Opioid / agonists
  • Receptors, Opioid / metabolism
  • Sulfur Radioisotopes

Substances

  • Analgesics, Opioid
  • Benzamides
  • Oligopeptides
  • Piperazines
  • Receptors, Opioid
  • Sulfur Radioisotopes
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • deltorphin II, Ala(2)-
  • 4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • GTP-Binding Proteins