Adenosine receptor link in an adrenal opioid-induced antinociception in the rat tail-flick test.
Intrathecal administration of substance P at the lower thoracic spinal level has an antinociceptive effect on reaction time in the tail-flick test; this response is blocked by naloxone i.v. but not by i.v. administration of opiate antagonists which do not cross the blood-brain barrier. As morphine-induced analgesia is blocked by adenosine antagonists, to determine whether this substance P-induced, opioid-mediated antinociception also includes a purine link, the adenosine receptor antagonist, caffeine, was given systemically 10 min prior to substance P administration. In control rats pretreated with saline, substance P (6.5 nmol) produced an increase in reaction time to about 160% of preadministration values at one min after intrathecal injection. The effect could also be observed at 6 min after this injection. Pretreatment with 16 or with 32 mg/kg of caffeine i.p. blocked the response to substance P, and produced a hyperalgesia similar to that reported in studies at the lumbo-sacral spinal level. These results indicate that the adrenal opioid-induced antinociception observed upon intrathecal administration of substance P at the lower thoracic level occurs via an adenosine link. This is the first demonstration of a purine link in the expression of antinociceptive effects of an endogenously released opioid.
Yashpal
K
K
Department of Physiology, McGill University, Montreal, Que., Canada.
Henry
J L
JL
D000241:Adenosine / Q000037:antagonists & inhibitors; D000704:Analysis of Variance; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D008297:Male; D009619:Nociceptors / Q000187:drug effects*; D010147:Pain Measurement; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D011983:Receptors, Purinergic / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology*
D011983:Receptors, Purinergic; D013373:Substance P; D002110:Caffeine; D000241:Adenosine