title: 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.
abstract: The authors systematically studied the release of the endogenous opioid peptides beta-endorphin and methionine (met)-enkephalin into the cerebrospinal fluid (CSF) during deep brain stimulation in patients suffering from otherwise intractable chronic pain. Nine patients were included in the study; six had stimulation electrodes placed in both the periventricular gray matter (PVG) and the thalamic nucleus ventralis posterolateralis (VLP) and three in the PVG only. Immunoreactivity of beta-endorphin and met-enkephalin (beta-EPir and MEir, respectively) was measured by radioimmunoassays in ventricular and lumbar CSF samples obtained before, during, and after stimulation. Prestimulation concentrations of beta-EPir and MEir were lower in ventricular than in lumbar CSF (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). Ventricular CSF concentrations of both beta-EPir and MEir increased significantly during PVG stimulation, whereas VPL stimulation was without effect. No changes were seen in lumbar CSF levels of the peptides during stimulation in either site. A significant inverse relationship was found between the "during:before stimulation" ratios of visual analog scale ratings and beta-EPir levels during PVG stimulation. The beta-EPir and MEir concentration during:before stimulation ratios were positively correlated, whereas no correlation was present in prestimulation samples from ventricular or lumbar CSF. High-performance liquid chromatography of ventricular CSF pools obtained during PVG stimulation revealed that major portions of beta-EPir and MEir eluted as synthetic beta-endorphin and met-enkephalin, respectively, thus documenting the release of beta-endorphin and met-enkephalin into ventricular CSF during PVG 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.
authors.affiliation: Department of Neurological Surgery, University of California Irvine School of Medicine, Orange.
authors.forename: R F
authors.initials: RF
authors.lastname: Young
authors.forename: F W
authors.initials: FW
authors.lastname: Bach
authors.forename: A S
authors.initials: AS
authors.lastname: Van Norman
authors.forename: T L
authors.initials: TL
authors.lastname: Yaksh
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D004599:Electric Stimulation Therapy; D004567:Electrodes, Implanted; D004744:Enkephalin, Methionine / Q000134:cerebrospinal fluid*; D005071:Evoked Potentials / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D010148:Intractable Pain / Q000134:cerebrospinal fluid / Q000503:physiopathology / Q000628:therapy*; D010487:Periaqueductal Gray / Q000502:physiology; D013787:Thalamic Nuclei / Q000502:physiology; D001615:beta-Endorphin / Q000134:cerebrospinal fluid*
chemical_list: D004744:Enkephalin, Methionine; D001615:beta-Endorphin