Corticotropin releasing hormone, interleukin-1 alpha, and tumor necrosis factor-alpha share characteristics of stress mediators.

Interleukin-1 alpha and tumor necrosis factor-alpha induce an increase in pain thresholds in the rat. We now show that also the corticotropin releasing hormone induces an analgesic effect that, similarly to what is observed with the two cytokines, is not reversible by naloxone. Moreover, we also show that after the administration of interleukin-1 alpha, tumor necrosis factor-alpha, and corticotropin releasing hormone, naloxone becomes analgesic itself. A similar observation was also made in the human and the experimental animal after exposure to stressful conditions. The results obtained suggest that the two cytokines share with corticotropin releasing hormone some characteristics of stress mediators.