POSITRON EMISSION TOMOGRAPHIC ANALYSIS OF CEREBRAL STRUCTURES ACTIVATED SPECIFICALLY BY REPETITIVE NOXIOUS HEAT STIMULI

1. To identify the forebrain and brain stem structures that are active during the perception of acute heat pain in humans, we performed (H2O)-O-15 positron emission tomographic (PET) analyses of cerebral blood flow (CBF) on nine normal volunteers while they received repetitive noxious(50 degrees C) and innocuous(40 degrees C) 5 s heat pulses to the forearm (average resting temperature of 31.8 degrees C). Each subject rated the subjective intensity of each stimulation series according to a magnitude estimation procedure in which 0 = no heat sensation, 7 = barely painful, and 10 = barely tolerable. 2. Three scans were performed at each temperature. Mean CBF images were created for each experimental condition and oriented onto standardized stereotaxic coordinates. Subtraction images were created between conditions for each subject and averaged across subjects. Volumes of interest (VOI) were chosen, based on a priori hypotheses and the results of previously published PET studies. In addition, a separate statistical summation analysis of individual voxels was performed. Statistical thresholds were established with corrections for multiple comparisons. 3. Significant CBF increases to 50 degrees C stimuli were found in the contralateral thalamus, cingulate cortex, S2 and S1 cortex, and insula. The ipsilateral S2 cortex and thalamus, and the medial dorsal midbrain and cerebellar vermis also showed significant CBF increases. All subjects rated the 50 degrees C stimuli as painful (average subjective rating = 8.9 +/- 0.9 SD) and the 40 degrees C stimuli as warm, but not painful (average subjective rating = 2.1 +/- 1.0). 4. To determine whether this result reflected the difference between perceived warmth and heat pain or between stimulus intensities only, an identical PET protocol was used for nine additional subjects except that both forearms were cooled to 21-25 degrees C while thermal pulses of 32 or 42 degrees C were applied during each scan. The subjects easily distinguished between the two stimuli but none was perceived as painful. The average subjective rating of the 32 degrees C stimuli was 1.3 +/- 1.1 and of the 42 degrees C stimuli, 4.0 +/- 1.5. No brain structures were activated significantly in this phase of the study. 5. The results are consistent with the interpretation that the structures showing significant CBF increases are components of the neural mechanisms mediating the sensory, and, possibly, the affective and premotor components of acute, repetitive heat pain.