Suppression of morphine withdrawal by electroacupuncture in rats: dynorphin and kappa-opioid receptor implicated

Our previous work has demonstrated that 100-Hz electroacupuncture (EA) or 1 00-Hz transcutaneous electrical nerve stimulation (TENS) was very effective in ameliorating the morphine withdrawal syndrome in rats and humans. The m echanism was obscure. (1) Rats were made dependent on morphine by repeated morphine injections (5-140 mg/kg, s.c., twice a day) for eight days. They w ere then given 100-Hz EA for 30 min 24 h after the last injection of morphi ne. A marked increase in tail flick latency (TEL) was observed. This effect of 100-Hz EA could be blocked by naloxone (NX) at 20 mg/kg, but not at 1 m g/kg, suggesting that 100-Hz EA-induced analgesia observed in morphine-depe ndent rats is mediated by K-opioid receptors. (2) A significant decrease of the concentration of dynorphin A (1-17) immunoreactivity (-ir) was observe d in the spinal perfusate in morphine-dependent rats, that could be brought back to normal level by 100-Hz EA. (3) 100-Hz EA was very effective in sup pressing NX-precipitated morphine withdrawal syndrome. This effect of EA co uld be prevented by intrathecal administration of nor-BNI (2.5 mu g/20 mu l ), a kappa-opioid receptor antagonist, or dynorphin A (1-13) antibodies (25 mu g/20 mu l) administered 10 min prior to EA. Ln conclusion, while the st eady-state spinal dynorphin release is low in morphine-dependent rats, it c an be activated by 100-Hz EA stimulation, which may be responsible for elic iting an analgesic effect and ameliorating morphine withdrawal syndrome, mo st probably via interacting with K-opioid receptor at spinal level. (C) 199 9 Elsevier Science B.V. All rights reserved.