RELEASE OF BETA-ENDORPHIN AND METHIONINE-ENKEPHALIN INTO CEREBROSPINAL-FLUID DURING DEEP BRAIN-STIMULATION FOR CHRONIC PAIN - EFFECTS OF STIMULATION LOCUS AND SITE OF SAMPLING

The authors systematically studied the release of the endogenous opioi d peptides beta-endorphin and methionine (met)-enkephalin into the cer ebrospinal fluid (CSF) during deep brain stimulation in patients suffe ring from otherwise intractable chronic pain. Nine patients were inclu ded in the study; six had stimulation electrodes placed in both the pe riventricular gray matter (PVG) and the thalamic nucleus ventralis pos terolateralis (VLP) and three in the PVG only. Immunoreactivity of bet a-endorphin and met-enkephalin (beta-EPir and MEir, respectively) was measured by radioimmunoassays in ventricular and lumbar CSF samples ob tained before, during, and after stimulation. Prestimulation concentra tions of beta-EPir and MEir were lower in ventricular than in lumbar C SF (6.6 +/- 0.5 vs. 13.7 +/- 1.0 pmol/liter, p = 0.0001, for beta-EPir ; 33.6 +/- 5.1 vs. 48.3 +/- 3.2 pmol/liter, p < 0.05, for MEir). Ventr icular CSF concentrations of both beta-EPir and MEir increased signifi cantly during PVG stimulation, whereas VPL stimulation was without eff ect. No changes were seen in lumbar CSF levels of the peptides during stimulation in either site. A significant inverse relationship was fou nd between the ''during:before stimulation'' ratios of visual analog s cale ratings and beta-EPir levels during PVG stimulation. The beta-EPi r and MEir concentration during:before stimulation ratios were positiv ely correlated, whereas no correlation was present in prestimulation s amples from ventricular or lumbar CSF. High-performance liquid chromat ography of ventricular CSF pools obtained during PVG stimulation revea led that major portions of beta-EPir and MEir eluted as synthetic beta -endorphin and met-enkephalin, respectively, thus documenting the rele ase of beta-endorphin and met-enkephalin into ventricular CSF during P VG stimulation. The finding of a direct relationship between beta-EPir release and pain alleviation may suggest a role for beta-endorphin in the analgesic mechanism of PVG stimulation.