Psychophysical studies have shown that patients with fibromyalgia (FM) have cutaneous heat and pressure thresholds that are lower and ratings of these stimuli that are higher than normal. Patients with the chronic pain of arthritis (CPA) have similar, but less severe, hypersensitivity to cutaneous heat and pressure stimuli. These abnormalities may reflect an amplification of forebrain nociceptive processing due to continual nociceptive input (CPA), or primary adaptive changes in CNS nociceptive processing (FM). We will obtain psychophysical measurements of the thresholds and perceived intensities and unpleasantness of cutaneous heat and somatic pressure stimuli in all subjects. We will use H215O positron emission tomography (PET) to test the overall hypothesis that FM and CPA patients have correspondingly larger stimulus-evoked increases in regional cerebral blood flow (rCBF) within bilateral volumes of interest (VOI; thalamus, insula, and the sensorimotor (S1/M1), S2, anterior cingulate, and premotor (B6) cortices) than normal subjects. Because FM occurs primarily in women, we will study two groups of right-handed female patients: 20 with FM and 20 with CPA, and compare their rCBF responses to those of 20 normal women within the same age range (20-50 years). Patients will rate their clinical pain at or above 4 on a visual analog scale of pain (VAS; 0-10) and will complete a short-form McGill Pain Questionnaire (VAS, MPQ). Standard VOI will be developed in normal subjects from peak rCBF increases within the above structures in response to heat stimuli applied at 35EC, heat pain threshold (HPT), heat pain tolerance (Hptol), and at 3 additional intensities anchored symmetrically around HPT and below Hptol. These standard VOI and stimulus intensities will be used to determine the correlation between rCBF increases and applied stimulus intensity and perceived unpleasantness, as estimated with a VAS, in normal subjects and in patients with FM or CPA who have not been taking opioid analgesic or psychoactive medication for one month. We predict that the psychophysical responses, and the rCBF responses within one or more VOI will be larger in FM and CPA patients than in normal subjects. These same studies will be performed again after all patients have been taking nortriptyline (NT) and/or physical therapy (PT) for approximately one year. Normal subjects will take NT for 3 weeks before the second PET scan (1 year later). We predict that both patient groups, but not normal subjects, will show clinical pain scores, stimulus-evoked psychophysical responses, and rCBF responses, in one or more VOI, that are less than those obtained before NT or PT treatment. We will also examine differences between FM and CPA patients. Support for the overall and correlative hypotheses will constitute evidence that, in the absence of peripheral causes, the pain experienced by FM and CPA patients is due, at least in part, to abnormal central nociceptive processing mechanisms.
