[Chronopharmacological features of the pain-relieving effects of analgesics]

The circadian and ultradian rhythms of threshold pain sensitivity to different nociceptive stimuli-thermal (tail-flick) and mechanical (tail pressure)--were revealed by cosinor analysis in male rats without or after drug administration. The minimal pain sensitivity to mechanical pressure was observed during the first half of the dark phase, that to thermal stimulus during the first half of the light phase. Biorhythms of thermal pain sensitivity of mice and rats are characterized by the same parameters. Opioid receptor morphine, buprenorphine, butorphanol, morphoceptin, and U-50,488H showed individual day patterns of analgesia, which depended on the type of nociceptive stimuli. The most distinct shifts of the acrophase of circadian rhythm from the control were observed after morphine, butorphanol, and U-50,488H. A conclusion is made that drug interaction with kappa-opiate receptors contributes to the regulation of pain sensitivity biorhythms.