Release of β-endorphin and methionine-enkephalin into cerebrospinal fluid during deep brain stimulation for chronic pain

Abstract

✓ The authors systematically studied the release of the endogenous opioid peptides β-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 β-endorphin and met-enkephalin (β-EPir and MEir, respectively) was measured by radioimmunoassays in ventricular and lumbar CSF samples obtained before, during, and after stimulation. Prestimulation concentrations of β-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 β-EPir; 33.6 ± 5.1 vs. 48.3 ± 3.2 pmol/liter, p < 0.05, for MEir). Ventricular CSF concentrations of both β-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 β-EPir levels during PVG stimulation. The β-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 β-EPir and MEir eluted as synthetic β-endorphin and met-enkephalin, respectively, thus documenting the release of β-endorphin and met-enkephalin into ventricular CSF during PVG stimulation. The finding of a direct relationship between β-EPir release and pain alleviation may suggest a role for β-endorphin in the analgesic mechanism of PVG stimulation.