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-endorphin immunoreactivity into perfusate. The release was blocked by intrathecal pretreatment with 1.25 mg lidocaine and the capsaicin receptor antagonist capsazepine (92 mu g), showing that the release is caused 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 the AMPA receptor antagonist NBQX(6 mu g) yielded no significant inhibition. Surprisingly, morphine (30 mu g) and sufentanil(1.5 mu g) did not prevent release of beta-endorphin immunoreactivity, although blocking the cardiovascular responses to a noxious heat stimulus. High performance liquid chromatography characterization of perfusates collected after capsaicin injection showed that all beta-endorphin immunoreactivity coeluted with authentic beta-endorphin(1-31). beta-Endorphin immunoreactivity in plasma was increased 10 min, but not 25 min, after capsaicin injection. Capsaicin injection abolished the motor and cardiovascular responses to tail immersion in 52.5 degrees C water. Addition of MK-801 (10(-4) mol/l) to the lateral ventricle-cisterna magna perfusate blocked the capsaicin-induced beta-endorphin release, showing that our previous demonstration of an NMDA receptor regulating arcuate nucleus beta-endorphin neuron activity has functional significance. We conclude that in this in vivo, anesthetized preparation including three hot water tail immersions, beta-endorphin can be released into a ventriculo-cisternal perfusate, by activation of the central axons of small primary afferent neurons by capsaicin. These data support the idea that central beta-endorphin may be released in response to prolonged, intense noxious stimulation.