RELEASE OF BETA-ENDORPHIN IMMUNOREACTIVITY INTO VENTRICULOCISTERNAL PERFUSATE BY LUMBAR INTRATHECAL CAPSAICIN IN THE RAT

A model employing perfusion of artificial cerebrospinal fluid from the lateral ventricle to the cisterna magna in the halothane anesthetized rat was used to study beta-endorphin release in the brain. Injection of 75 mu g capsaicin into the lumbar intrathecal space released beta-e ndorphin immunoreactivity into perfusate. The release was blocked by i ntrathecal pretreatment with 1.25 mg lidocaine and the capsaicin recep tor antagonist capsazepine (92 mu g), showing that the release is caus ed by binding of capsaicin to a spinal receptor. The release was also blocked by intrathecal pretreatment with the NMDA antagonist MK-801 (3 mu g) and the NK-1 receptor antagonist CP96,345 (200 mu g), whereas t he AMPA receptor antagonist NBQX(6 mu g) yielded no significant inhibi tion. Surprisingly, morphine (30 mu g) and sufentanil(1.5 mu g) did no t prevent release of beta-endorphin immunoreactivity, although blockin g the cardiovascular responses to a noxious heat stimulus. High perfor mance liquid chromatography characterization of perfusates collected a fter capsaicin injection showed that all beta-endorphin immunoreactivi ty coeluted with authentic beta-endorphin(1-31). beta-Endorphin immuno reactivity in plasma was increased 10 min, but not 25 min, after capsa icin injection. Capsaicin injection abolished the motor and cardiovasc ular responses to tail immersion in 52.5 degrees C water. Addition of MK-801 (10(-4) mol/l) to the lateral ventricle-cisterna magna perfusat e blocked the capsaicin-induced beta-endorphin release, showing that o ur previous demonstration of an NMDA receptor regulating arcuate nucle us beta-endorphin neuron activity has functional significance. We conc lude that in this in vivo, anesthetized preparation including three ho t water tail immersions, beta-endorphin can be released into a ventric ulo-cisternal perfusate, by activation of the central axons of small p rimary afferent neurons by capsaicin. These data support the idea that central beta-endorphin may be released in response to prolonged, inte nse noxious stimulation.