Corticotropin-releasing-hormone lacks analgesic properties: an experimental study in humans, using non-inflammatory pain

The antinociceptive potency of corticotropin-releasing-hormone (CRH) has be en established in several animal studies in which both central and peripher al sites of action were considered. However, there have not yet been any ex perimental trials, besides one attempt using clinical dental pain demonstra ting the potential analgesic properties of CRH in humans. For this reason, we studied the effect of CRH on experimental heat pain sensitivity in 18 he althy men, using a double-blind, cross-over and placebo-controlled design. A dose of 100 mu g (i.v.) was chosen because of its well-known neuroendocri ne effects in humans. The pain parameters assessed were, visual analog scal e (VAS) ratings for pain intensity and pain unpleasantness, pain thresholds and scores for discrimination ability. To differentiate between a direct a nalgesic effect of CRH and indirect effects via evoked hormonal responses i n the hypothalamic-pituitary-adrenocortical (HPA) system (beta-endorphin, A CTH, cortisol), CRH was applied with and without a pre-treatment with dexam ethasone. In neither of the two conditions was there any systematic change in our pain parameters. This failure to find any evidence suggesting an ana lgesic action of CRH or of the subsequent hormones of the HPA system was ob tained despite the fact that CRH produced clear neuroendocrine responses su ch as increases in the plasma concentration of beta-endorphin and cortisol. It is unclear whether the lack of analgesic action of CRH is due to its no n-existence in humans, due to the use of a pain model which does not assess minute changes in pain sensitivity and does not trigger substantial inflam matory responses, or due to an insufficient dose of CRH. (C) 1999 Internati onal Association for the Study of Pain. Published by Elsevier Science B.V.