The medial prefrontal cortex has been implicated in pain perception by recent anatomical, physiological, and functional imaging data demonstrating that frontal and anterior cingulate cortices receive inputs related to nociception; neurosurgical case reports suggest that lesions involving these areas may specifically reduce the affective or emotional component of chronic intractable pain. We examined this hypothesis more closely by assessing psychophysical ratings of (1) warmth, pain intensity, and unpleasantness evoked by phasic thermal stimuli, (2) tolerance to tonic cold stimuli, and (3) perceived intensity of visual stimuli, both before and after neurosurgical lesions of the fiber tracts connecting the frontal lobes to subcortical structures. A 22-year-old male, with no history of chronic pain, underwent psychophysical testing 3 days before, 5 days after, and 6 months after receiving bilateral lesions of the anterior internal capsule (aIC), performed as treatment for obsessive-compulsive disorder. In each session, the patient rated the intensity and unpleasantness of 5-sec cutaneous heat stimuli (39-47 degrees C); pain tolerance was measured by means of a cold-pressor test (hand immersion in 1 degrees C water). The patient was able to differentially rate the intensities of heat stimuli during both pre- and postsurgical testing sessions (p < 0.001). However, he rated heat stimuli as less intense 5 days after surgery than during presurgical testing (p < 0.001), with significant decreases in both pain intensity (p < 0.005) and unpleasantness (p < 0.05). Likewise, the patient described the cold-water immersion as less painful following surgery, although his tolerance times were substantially shorter than those of the presurgical evaluation. Ratings of visual stimulus intensity did not differ across the pre- and postsurgical testing periods, suggesting that changes in pain perception were not related to attentional or cognitive deficits. Magnetic resonance imaging 5 days following surgery revealed bilateral lesions and edema centered in the aIC, with some edema in the left frontal lobe. Those 6 months later showed substantially smaller lesions involving less than half of the aIC and no edema; pain ratings and cold-water tolerance measured at that time indicated a substantial return toward the patient's presurgical values. These data suggest that blocking subcortical input to the anterior cingulate and frontal cortices reduces both the perceived intensity and the unpleasantness of noxious stimuli; reduced cold tolerance times--in the face of decreased pain perception--may reflect a disinhibition of cortical control on spinal reflexes.(ABSTRACT TRUNCATED AT 400 WORDS)