Corticotropin-releasing-hormone lacks analgesic properties: an experimental study in humans, using non-inflammatory pain.
The antinociceptive potency of corticotropin-releasing-hormone (CRH) has been established in several animal studies in which both central and peripheral sites of action were considered. However, there have not yet been any experimental trials, besides one attempt using clinical dental pain demonstrating the potential analgesic properties of CRH in humans. For this reason, we studied the effect of CRH on experimental heat pain sensitivity in 18 healthy men, using a double-blind, cross-over and placebo-controlled design. A dose of 100 microg (i.v.) was chosen because of its well-known neuroendocrine effects in humans. The pain parameters assessed were, visual analog scale (VAS) ratings for pain intensity and pain unpleasantness, pain thresholds and scores for discrimination ability. To differentiate between a direct analgesic effect of CRH and indirect effects via evoked hormonal responses in the hypothalamic-pituitary-adrenocortical (HPA) system (beta-endorphin, ACTH, cortisol), CRH was applied with and without a pre-treatment with dexamethasone. In neither of the two conditions was there any systematic change in our pain parameters. This failure to find any evidence suggesting an analgesic action of CRH or of the subsequent hormones of the HPA system was obtained despite the fact that CRH produced clear neuroendocrine responses such 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 non-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 inflammatory responses, or due to an insufficient dose of CRH.
Lautenbacher
S
S
Department of Psychiatry and Psychotherapy, Philipps-University of Marburg, Rudolf-Bultmann-Str. 8, 35033, Marburg, Germany. lautenba@post.med.uni-marburg.de
Roscher
S
S
Kohl
G
G
Vedder
H
H
Krieg
J
J
D000328:Adult; D000700:Analgesics / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D018592:Cross-Over Studies; D003907:Dexamethasone / Q000494:pharmacology; D004311:Double-Blind Method; D005069:Evaluation Studies as Topic; D006358:Hot Temperature; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D001615:beta-Endorphin / Q000097:blood
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D001615:beta-Endorphin; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone