Appearance of beta-endorphin-like immunoreactivity in human ventricular cerebrospinal fluid upon analgesic electrical stimulation.

Abstract

jt-Endorphin-like immunoreactivity in human ventricular cerebrospinal fluid was measured with a specific radioimmunoassay. The subjects were undergoing a surgical procedure for relief of chronic intractable pain. This procedure involved the focal stimulation of a medial thalamic site adjacent to the wall of the third ventricle. Samples were collected before and during the analgesic stimulation. No f-endorphin-like immunoreactivity could be detected prior to stimulation, suggesting that baseline levels are below 25 fmol/ml of cerebrospinal fluid. Electrical stimulation led to substantial increases (13-to 20-fold) in immunoreactive material in every subject. These results suggest that ,kendorphin-like material can be released into the ventricular system and may contribute to the pain blockade that results from periventricular stimulation.The isolation and characterization of f3-endorphin from camel (1), sheep (2), and human (2, 3) pituitaries rapidly led to its identification as an endogenous opioid (1-4). Administration of this 31-amino-acid peptide to laboratory animals results in phenomena like those associated with opiates, including naloxone-reversible analgesia (5-10), tolerance (8-11), and dependence (8,11 Electrical stimulation of the brain has been shown to elicit analgesia in rat (26) and cat (27). This analgesia bears many of the characteristics of opiate action, including partial reversal with the opiate antagonist naloxone (28-30) and the development of tolerance to and cross-tolerance with morphine (31). However, these effects are only partial, suggesting a role of nonopiate as well as opiate mechanisms in this method of pain control. This work has been extended to the human clinical situation. Patients suffering from chronic intractable pain derive long-term relief from the stimulation of medial thalamic and periaqueductal sites (32,33). Stimulation of a site in the vicinity of the posterior commissure, immediately adjacent to the ventricular wall at the level of the nucleus parafascicularis, has been found to combine excellent analgetic effectiveness with minimal side effects. The characteristics of the pain relief obtained from such stimulation have been described (32,33). This stimulation-induced analgesia in man also appears to have an opioid component, because it has been shown to be naloxone reversible (34, 35) and to be accompanied by a rise in enkephalin-like opioid material in the cerebrospinal fluid (CSF) (36). Because the stimulation site in humans is homologous to a region in rodents particularly rich in (3-endorphin activity, we have examined the effect of its stimulation on (3-endorphin immunoreactivity in CSF. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. METHODS

Effect of naloxone on plasma concentrations of prolactin and LH in lactating sows

“…However, the present results seem to indicate that both high prolactin and low LH concentrations are the results of the same factor, acting through an opioid-mediated mechanism. This is supported by the results of previous experiments in which bromocriptine suppressed prolactin concentrations in lactating sows without influencing LH values (Seren et al, 1984;Mattioli & Seren, 1985 (Akil, Richardson, Barchas & Li, 1978;Akil & Watson, 1980), it might be supposed that a stimulus as potent as suckling would increase the production of opiates. Anatomical bases for such an hypothesis have been shown by Martin & Vogit (1981) and Vanderhaeghen, Lostra, Liston & Rossier (1983) Ellendorff, Elsaesser, Parvizi, Schäkel & Smidt (1985) reported that oxytocin administration in sows after weaning maintains the anoestrus.…”

Effects of Acute Behavioral Stress on Plasma and Cerebrospinal Fluid ACTH and β-Endorphin in Rhesus Monkeys

“…Direct stimulation of the brain in the areas of these peptide systems, however, causes a rise in CSF ACTH and |)-E and a concomitant physiologic re sponse (analgesia) [1,II,12]. Despite this evidence that CSF ACTH and P-E concentrations may reflect brain activ ity, the value of CSF measurements in neuropsychiatrie ill ness remains speculative [22,29,30].…”

“…31, 35]. The precise relationship between brain and CSF concentrations of these hormones is unknown, but there is evidence that CSF concentrations of ACTH, p-E, and other neuropeptides may reflect brain activity [1,6, II,12]. Krieger [22] and others [30] have suggested that assessment of ACTH, p-E, and other neuropeptide concentrations in CSF may provide information to further the understanding of various neuropsychiatric illnesses.…”

From the Golgi–Cajal mapping to the transmitter-based characterization of the neuronal networks leading to two modes of brain communication: Wiring and volume transmission

“…In adulthood, a number of biologically active molecules have been proposed to represent CSF signals (Segal, 2000;Brightman and Kaya, 2000). Of special interest are molecules affecting global functions such as sleep and circadian rhythms (Silver et al, 1996;Skinner and Malpaux, 1999), interleukin-1β modulating inflammation and sickness behavior (Krueger and Majde, 1995;Jansson, 1999;Jansson et al, 2000) and β-endorphin being essential for self and species survival (Akil et al, 1978;Bloom et al, 1978;Agnati et al, 1986a;Fuxe et al, 1988a;see Höistad et al, 2005). For a role of CSF signals in diseases of the nervous system, see Fishman (1992).…”