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Acute studies performed in five patients indicate that electrical stimulation of the brain could be a powerful tool for the reduction or control of intractable pain. While chronic or spontaneous pain could be relieved by stimulation of the periaqueductal gray matter, the accompanying side effects render it impossible to stimulate this site regularly. On the other hand, stimulation of medial thalamic sites, particularly medial to the nucleus parafascicularis, yielded good relief of chronic pain at parameters which did not cause many undesirable side effects. The same parameters also produced inhibition of acute pain in two of the five patients.

Thirty patients were operated upon, with chronic implantation of self-stimulating devices for stimulation of the posterior periventricular gray matter for pain control. Three patients required removal of the electrodes because of failure of adequate pain control during the period of percutaneous testing, and five patients report on long term follow-up that they have had no pain relief with stimulation, and have discontinued it. Four patients describe minor relief of pain, and 18 patients report significant relief of pain with stimulation. Therefore, 18 patients, or 66% of the 27 patients having implantation, are considered to have had successful operations, and 12 of the patients are considered failures. Stimulation for brief periods of time, such as 5 to 30 minutes every 2 to 12 hours has been found adequate for control of chronic pain with minimal side effects and a low complication rate.

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Intermittent explosive disorder (IED) is characterized by a dysfunction in the greater limbic system leading an individual to experience sudden aggressive behavior with little or no environmental perturbation. This report describes a procedure for the treatment of IED in a 19-year-old woman with a history of IED, having had episodes of severe violent attacks against family, dating to early childhood. Due to the severity and intractability of the illness, deep brain stimulation was performed, targeting the orbitofrontal projections to the hypothalamus. The patient's history and the procedure, management, and rationale are described in detail.

Electrical stimulation of the periventricular gray matter is an effective means of relieving several types of pain without destruction of neural tissue. The effects are long lasting, often bilateral, and with judicious use do not appear subject to adaptation. However, sustained uninterrupted stimulation for several hours does lead to a reversible decrease in effectiveness. Side effects from stimulation are minimal and cause little or no untoward emotional changes. The results are discussed in terms of activation of an endogenous pain inhibitory mechanism that involves naturally occurring opiate-like factors such as the enkephalins and endorphins.

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

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