IMAGING THE BRAIN IN PAIN - POTENTIALS, LIMITATIONS, AND IMPLICATIONS

The recent development of methods for imaging the functional activity of the waking human brain has added a highly important dimension to neuroscience in general and to the study of pain mechanisms in particular. Tomographic images of changes in regional cerebral blood flow (rCBF) can now be constructed, using freely diffusible radiotracers such as (H2O)-O-15, with a half-life of 2 min. Image resolution is now on the order of 3 to 5 ml in volume, and stereotaxic reconstruction methods allow the identification of changes in rCBF within cerebral cortical and subcortical structures, including those within the posterior fossa. Subtracting images obtained during control conditions from those obtained during test or experimental conditions produces images that can reveal increases in cerebral blood flow that are associated uniquely with the test condition. There is substantial evidence that these increases in rCBF are generated by metabolic by-products of synaptic activity, probably including nitric oxide (NO). Positron-emission tomographic (PET) images of rCBF have been made of the brains of normal subjects receiving repetitive heat stimulation of one arm. Subtraction images were made from scans taken during stimulation with innocuous (<45 degrees C) as compared with noxious (>45 degrees C) heat. Taken together, the data obtained from three different PET facilities, including our own, show a pattern of rCBF activation that includes structures that may be assumed, on the basis of other evidence, to mediate different components of pain and pain modulation. Thus, rCBF activation of the contralateral ventral thalamus and primary (S1) cortex probably represents the sensory-discriminative component of pain, while the activation of structures associated with autonomic and limbic-system functions, such as the insula and anterior cingulate cortex, may reflect the affective aspect of the pain experience. The activation of pain-modulatory and premotor systems may be represented by the increased rCBF in the dorsomedial midbrain and midline cerebellum, respectively. However, the function subserved by each of the components of this pain-related rCBF activation pattern can be determined only by further experiments directed toward an analysis of this inter-regional network.