Forebrain mechanisms of nociception and pain: Analysis through imaging

Pain is:a unified experience composed of interacting discriminative, affect ive-motivational, and cognitive components, each of which is mediated and m odulated through forebrain mechanisms acting at spinal, brainstem, and cere bral levels. The size of the human forebrain in relation to the spinal cord gives anatomical emphasis to forebrain control over nociceptive processing . Human forebrain pathology can cause pain without the activation of nocice ptors. Functional imaging of the normal human brain with positron emission tomography (PET) shows synaptically induced increases in regional cerebral blood flow (rCBF) in several regions specifically during pain. We have exam ined the variables of gender, type of noxious stimulus, and the origin of n ociceptive input as potential determinants of the pattern and intensity of rCBF responses. The structures most consistently activated across genders a nd during contact heat pain, cold pain, cutaneous laser pain or intramuscul ar pain were the contralateral insula and anterior cingulate cortex, the bi lateral thalamus and premotor cortex, and the cerebellar vermis, These regi ons are commonly activated in PET studies of pain conducted by other invest igators, and the intensity of the brain rCBF response correlates parametric ally with perceived pain intensity. To complement the human studies, we dev eloped an animal model for investigating stimulus-induced rCBF responses in the rat. In accord with behavioral measures and the results of human PET, there is a progressive and selective activation of somatosensory and limbic system structures in the brain and brainstem following the subcutaneous in jection of formalin. The animal model and human PET studies should be mutua lly reinforcing and thus facilitate progress in understanding forebrain mec hanisms of normal and pathological pain.