In the present study the effects of intravenously administered
corticotropin-releasing hormone (CRH) on the release of
proopiomelanocortin (
POMC) derivatives such as
adrenocorticotropic hormone (
ACTH),
beta-lipotropin (
beta-LPH) and
beta-endorphin (beta-END) as well as direct effects of CRH on
pain sensitivity were examined. In 16 healthy volunteers we studied the effects of 100 microg intravenously administered CRH in absence or presence of 12 mg
naloxone on heat or pressure
pain sensitivity, using a double-blind, cross-over and placebo-controlled design. To evaluate
analgesic effects of CRH via release of
POMC derivatives, we determined plasma concentrations of beta-END-immunoreactive material (IRM), authentic beta-END (beta-END(1-31)) and
beta-LPH IRM, in parallel with heat and pressure
pain tolerance thresholds before and 15 and 30 min
after treatment with CRH (or placebo), and 5 min after
naloxone (or placebo) administration which was administered 40 min after CRH (or placebo) injection. CRH increased levels of beta-END IRM, beta-END(1-31) and
beta-LPH IRM. As compared to beta-END IRM levels measured by a commercial RIA kit, the beta-END(1-31) levels determined by a highly specific two-site RIA, proved to be remarkably small. Furthermore, CRH did not induce increases of heat
pain tolerance thresholds, but of pressure
pain tolerance thresholds, which, however, were not reversible by
naloxone. Neither beta-END nor
beta-LPH IRM nor beta-END(1-31) levels correlated with heat or pressure
pain tolerance thresholds. We conclude that CRH does not modulate heat, but pressure
pain;
POMC derivatives like beta-END IRM, beta-END(1-31) or
beta-LPH do not mediate this effect.