Analgesic effect of thalidomide on inflammatory pain

Abstract

Tumor necrosis factor α (TNF-α) may have a pivotal role in the genesis of mechanical inflammatory hyperalgesia in rats and in the nociceptive writhing response in mice. Thalidomide has been shown to selectively inhibit TNF-α production. We therefore investigated the effect of thalidomide on these responses as well as on the hot plate response in mice. Hyperalgesic responses to intraplantar (i.pl.) injections of carrageenin or bradykinin, which act by stimulating TNF-α release, but not responses to TNF-α or prostaglandin E 2, were inhibited in a dose-dependent manner by pretreatment of the animals with thalidomide. The nociceptive writhing responses induced by intraperitoneal (i.p.) injections of zymosan or acetic acid were also inhibited in a dose-dependent manner by pretreatment of mice with thalidomide. Moreover, the thalidomide pretreatment also reduced the TNF-α mRNA levels in the peritoneal cells induced by injection of zymosan in mice. The analgesic effect of thalidomide is not due to a central effect, since the drug had no effect in the hot plate test. The demonstration that thalidomide is able to inhibit inflammatory hyperalgesia in rats and the writhing nociceptive response in mice suggests that these analgesic effects seem to be a consequence of the inhibition of TNF-α production, and indicates the need for investigations on the possibility of the use of thalidomide for the treatment of pain refractory to classical non-narcotic analgesics.