Central mechanism of indomethacin analgesia.
The analgesic effect of indomethacin was investigated by using the visceral pain model in rabbits. After intravenous administration of indomethacin (2 mg/kg), the maximum increase of the visceral pain threshold was 0.42 +/- 0.31 mA (P < 0.05). The analgesic effect lasted 40 min. After intraventricular microinjection of indomethacin (50 micrograms), the maximum increase of the visceral pain threshold was 0.37 +/- 0.43 mA. After intravenous administration of indomethacin, the content of norepinephrine in perfusates of rabbit fourth ventricle was significantly increased from 18.10 +/- 8.05 to 32.16 +/- 6.15 mg/40 microliters (P < 0.05), compared with data for the control group. The content of beta-endorphin in the perfusate after indomethacin administration was decreased from 5-25 min and slightly increased from 25-35 min, compared with the data for the control group, but there was no significant difference (P > 0.05). Furthermore, intraventricular microinjection of phentolamine (50 micrograms) could block the analgesic effect of an intravenous injection of indomethacin, while naloxone could not. The results imply that prostaglandins of the central nervous system could induce hyperalgesia. Indomethacin injected centrally and peripherally has an analgesic effect on visceral pain. This analgesic effect is mediated by alpha-adrenoceptors. beta-Endorphin does not participate in the analgesic action of indomethacin.
Hu
X H
XH
Department of Neurobiology, Shanghai Medical University, People's Republic of China.
Tang
H W
HW
Li
Q S
QS
Huang
X F
XF
D000700:Analgesics / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D005260:Female; D007213:Indomethacin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects; D010646:Phentolamine / Q000494:pharmacology; D011817:Rabbits; D001615:beta-Endorphin / Q000494:pharmacology
D000700:Analgesics; D009270:Naloxone; D001615:beta-Endorphin; D009638:Norepinephrine; D007213:Indomethacin; D010646:Phentolamine