Differential actions of intrathecal naloxone on blocking the tail-flick inhibition induced by intraventricular beta-endorphin and morphine in rats.
In the present study, it is proposed that the opioids applied to supraspinal brain sites produced their analgesic effects by the activation of different descending pain inhibitory systems. The blockade of the spinal endorphinergic system by intrathecal naloxone on the production of tail-flick inhibition induced by intraventricular beta-endorphin and morphine was then studied. Intraventricular injection of beta-endorphin and morphine produced an inhibition of the tail-flick response to the heat stimulus in rats. Intrathecal injection of naloxone at doses of 0.4 to 40 micrograms caused a dose-related blockade of the inhibition of the tail-flick response induced by intraventricular injection of beta-endorphin, and a high dose of naloxone (40 micrograms) completely blocked the tail-flick inhibition induced by intraventricular beta-endorphin (16 micrograms). On the other hand, intrathecal naloxone (12-120 micrograms) had only a very weak effect on the tail-flick inhibition induced by intraventricular morphine (40 micrograms). Intraventricular injection of naloxone at doses of 1.2 to 12 micrograms equally antagonized in a dose-dependent manner the tail-flick inhibition induced by intraventricular beta-endorphin and morphine. The results indicate that a spinal naloxone-sensitive endorphinergic system is involved in the production of beta-endorphin but not morphine-induced tail-flick inhibition, and suggest that intraventricular beta-endorphin and morphine elicit their pharmacological actions via the activation of different descending pain inhibitory systems; descending epsilon and mu systems for beta-endorphin and morphine, respectively, are proposed.
Tseng
L F
LF
Fujimoto
J M
JM
D000698:Analgesia; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D004723:Endorphins / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D001615:beta-Endorphin
D004723:Endorphins; D009270:Naloxone; D001615:beta-Endorphin; D009020:Morphine