Preoperative concentration of beta-lipotropin immunoreactive material in cerebrospinal fluid: a predictor of postoperative pain?

Levels of beta-endorphin immunoreactive material (IRM) in cerebrospinal fluid (CSF) have been reported to correlate inversely with postoperative morphine requirement. Considering proopiomelanocortin (POMC) derivatives as predictors for sensitivity to postoperative pain, we determined authentic beta-endorphin (beta-endorphin(1-31)), beta-lipotropin IRM, N-acetyl-beta-endorphin IRM and ACTH in CSF of 17 patients undergoing hip or knee arthroplasty, before surgery (t(A)), immediately after termination of propofol infusion and still under spinal anesthesia (t(B)), under postoperative pain (t(C)) and one day after surgery (t(D)); patients rated their severity of pain on a visual analogue scale (VAS) at those four times. In all patients CSF concentrations of N-acetyl-beta-endorphin IRM and beta-lipotropin IRM were found to be increased after terminating the propofol infusion with spinal anesthesia still effective at t(B). Patients did not feel pain at times t(A), t(B) or t(D); however, they reported moderate to considerable pain at t(C). There were no correlations of postoperative pain severity at t(C) with ACTH, beta-endorphin(1-31) or N-acetyl-beta-endorphin IRM concentrations in CSF. In contrast, we observed significant inverse correlations (Spearman's rank correlation coefficients between -0.83 and -0.85, p<0.01) for postoperative pain severity with beta-lipotropin IRM concentrations in CSF at t(C), and, in addition, at t(A), t(B) and t(D); thus, postoperative pain severity appeared to be dependent on a central system controlling sensitivity to pain, linked to a POMC system releasing beta-lipotropin IRM into CSF and already active at times t(A) and t(B). We conclude that beta-lipotropin IRM in CSF might be considered to serve as a predictor of sensitivity to postoperative pain.

Biological monitoring of experimental human exposure to hydrocarbon solvent mixtures.

The aim of the study was to develop and to validate a suitable analytical method in order to assess the internal exposure of persons to commercial products of hydrocarbon solvent mixtures (HSM). Twenty healthy volunteers were exposed to vapours of five commercial HSM for 8h at 200-1,000 mg/m(3) air. Aromatic-rich, aromatic-poor and aromatic-free HSM were used, as well as isohexane and technical hexane mixtures. A total of 300 exposures were carried out at rest or with an exercise period of 10 min/h at 50 and 75 W. Blood samples for the determination of the HSM were collected before and immediately after exposure. They were analyzed with a headspace analyzer by gas chromatography and mass spectrometry. The analytical method has detection limits of 2-50 microg HSM/L blood. With this method we obtained intra- and interassay variation coefficients of 3.7-15.1%, at concentrations of 53-1,500 microg HSM/L blood. The mean values of the HSM of the 20 volunteers after 8h range between 89 mug/L (technical hexane-mixture) and 1,369 microg/L blood (aromatic-free HSM) at rest. Physical exercises of 50 and 75 W, respectively, lead to a significant increase of the blood-concentrations by mean factors between 1.2 and 1.9 for the five HSM. In conclusion, our results demonstrate that physical activity should be considered in the setting of occupational exposure limits.

Corticotropin-releasing hormone reduces pressure pain sensitivity in humans without involvement of beta-endorphin(1-31), but does not reduce heat pain sensitivity.

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.

Effects of tourniquet-induced ischemia on the release of proopiomelanocortin derivatives determined in peripheral blood plasma.

Proopiomelanocortin (POMC) is expressed in pituitary, central nervous system, and in a few peripheral tissues. This study addresses the hypothesis that metabolic stressors, such as acidosis, may induce the release of POMC derivatives into the cardiovascular system not only from the pituitary but also from other sites of POMC expression. In our study, we investigated the liberation of POMC derivatives from peripheral tissues under a state of acidosis achieved by tourniquet-induced ischemia, alteration of lactate concentration, and base excess. In eight patients undergoing knee arthroplasty under spinal anesthesia, catheters were inserted into the femoral vein proximally to thigh tourniquet location. Blood was drawn from these catheters 5 min before and 40 s, 5 min, and 10 min after tourniquet deflation to measure plasma concentrations of N-acetyl-beta-endorphin immunoreactive material (IRM), beta-endorphin IRM, authentic beta-endorphin, adrenocorticotropin, lactate, pH, and base excess. In five of eight patients, we found a significant increase of beta-endorphin IRM levels 40 s after tourniquet deflation compared with predeflation levels; 5 and 10 min after tourniquet deflation, the beta-endorphin IRM levels were below the detection limit. Thus beta-endorphin IRM was released from ischemic limb tissues into the cardiovascular system. Only a small part of the determined beta-endorphin IRM corresponded to authentic beta-endorphin. Forty seconds after tourniquet deflation, the beta-endorphin IRM concentration correlated with base excess (r < 0.71; P < 0.05); no significant correlations were found with pH or lactate levels. Thus it was shown here for the first time that ischemic stress may induce the release of beta-endorphin IRM from nonpituitary tissues.