Pain associated with knee osteoarthritis (OA) is characterized by (a) high levels of variability amongindividuals; and (b) modest associations with radiographic measures of tissue damage. Ethnic background isone important factor that contributes to variation in pain reports and pain-related behavior. Recent studiesindicate that African-American, compared to white, individuals exhibit lower pain tolerance levels andrelatively impaired pain regulatory mechanisms (e.g., blood pressure responses to stressors). There also isevidence that endogenous opioid release contributes to the function of these mechanisms. The overall aimof the proposed study, then, is detemine whether changes in opioid neurotransmission evoked by thermalheat stimulation partially mediate ethnic differences in thermal pain responses among patients with knee OA.Thirty-six men (18 African-American, 18 white) with knee OA will undergo PET bain imaging with theopiodergic radioligand [18F] fluoroethyl-diprenorphine under two conditions: (a) exposure to thermal heatstimulation, tailored to individual pain thresholds, that will produce similar, moderate, levels of thermal painintensity across patients; and (b) exposure to thermal heat stimulation that will produce perceptions ofwarmth across patients (sensory control condition). Patients will produce visual analogue scale (VAS) ratingsof pain intensity and unpleasantness following stimulation. We expect that African-American, compared towhite patients, will (a) produce significantly greater increases in pain unpleasantness ratings; and (b) exhibitlower opioid neurotransmission in medial pain system structures (e.g., amygdala, anterior cingulate cortex)from sensory control to painful thermal heat stimulation, even after controlling for psychosocial variablessuch as depressive symptom levels. We also expect that stimulation-evoked change in opioidneurotransmission in medial pain system structures will partially mediate the ethnic group difference inchange in pain unpleasantness ratings. We anticipate that the proposed research will generate new sttudiesthat will lead to (a) improved understanding of additional physiologic or psychosocial variables that contributeto ethnic differences in pain responses and endogenous pain regulatory function; (b) development of new orrefinement of current pharmacologic or behavioral/psychosocial interventions for pain management; and (c)reductions in ethnic disparities in patients' expectations of and preferences for these interventions.
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