Cholecystokinin octapeptide (CCK-8): antagonism to electroacupuncture analgesia and a possible role in electroacupuncture tolerance.
The analgesic effect produced by electroacupuncture (EA) stimulation in the rat was dose-dependently antagonized by cholecystokinin octapeptide (CCK-8) administered intracerebroventricularly (i.c.v.) or intrathecally (i.th) at a dose range of 0.25-4 ng. This effect had an immediate onset and lasted for at least 4 h. CCK-8 per se, however, did not affect baseline tail flick latency. Rats subjected to prolonged EA stimulation developed EA tolerance as well as cross-tolerance to morphine. These tolerances could be postponed or reversed by i.c.v. or i.th injection of antiserum against CCK-8. While CCK-8 antagonized opioid analgesia, it did not affect analgesia induced by 5-hydroxytryptamine (5-HT) or norepinephrine (NE). Moreover, CCK-8 antiserum did not alter the basic level of nociception, nor did it potentiate EA analgesia in naive rats. It is concluded that prolonged EA stimulation results in a profound release of opioids which may trigger the release of CCK-8 in the central nervous system to counteract the opioid component of EA analgesia. This mechanism may account, at least in part, for the development of EA tolerance.
D015670:Acupuncture Therapy; D000818:Animals; D004599:Electric Stimulation Therapy / Q000379:methods; D005260:Female; D007106:Immune Sera / Q000008:administration & dosage / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D059408:Pain Management; D051381:Rats; D012044:Regression Analysis; D012701:Serotonin / Q000494:pharmacology; D012844:Sincalide / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D004561:Transcutaneous Electric Nerve Stimulation / Q000379:methods
D007106:Immune Sera; D012701:Serotonin; D009020:Morphine; D012844:Sincalide; D009638:Norepinephrine