Elevation of pain threshold to tooth shock by brain stimulation in primates

Electrical stimulation of the brain (ESB) for modulation of pain has been previously demonstrated in primates, but many of the sites which yield stimulation-produced analgesia (SPA) also elicit aversive side effects. In order to examine the aversive as well as analgesic effects of brain stimulation, nine rhesus monkeys (Macaca mulatta) were first trained to press a lever to escape or titrate noxious tooth shock. Stimulating electrodes were placed under the frontal cortex in 4 monkeys and were implanted in the diencephalon, brain stem, and cerebellum of five remaining monkeys. Diencephalic stimulation sites resulted in marked elevations of tooth shock threshold at ESB intensities which did not elicit aversive behaviors. The analgesic effects lasted up to 2 h past ESB offset. Moderate elevations of tooth shock threshold were also observed with orbital cortex stimulation. The midbrain central gray and the nucleus raphe magnus, however, did not greatly alter tooth shock level and typically resulted in aversive reactions. The diencephalic sites which elicited SPA also led to self-stimulation behavior, whereas stimulation of the brain stem or cerebellum usually resulted in escape responses. These findings thus indicate that, in primates, more effective relief of pain can be achieved with electrical activation of the medial diencephalon than with brain stem stimulation.