Cholecystokinin octapeptide (CCK-8): antagonism to electroacupuncture analgesia and a possible role in electroacupuncture tolerance

Pain. 1986 Oct;27(1):101-115. doi: 10.1016/0304-3959(86)90227-7.


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 ( 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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acupuncture Therapy*
  • Animals
  • Electric Stimulation Therapy* / methods
  • Female
  • Immune Sera / administration & dosage
  • Immune Sera / pharmacology
  • Injections, Spinal
  • Male
  • Morphine / pharmacology
  • Norepinephrine / pharmacology
  • Pain / physiopathology*
  • Pain Management
  • Rats
  • Regression Analysis
  • Serotonin / pharmacology
  • Sincalide / administration & dosage
  • Sincalide / pharmacology*
  • Time Factors
  • Transcutaneous Electric Nerve Stimulation* / methods


  • Immune Sera
  • Serotonin
  • Morphine
  • Sincalide
  • Norepinephrine