The effects of aging on experimental models of pain inhibition and facilitation

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DESCRIPTION (provided by applicant): Older adults are at increased risk to develop prolonged pain and experience greater pain-related loss of physical and psychosocial function compared to younger cohorts. We propose that changes in endogenous pain modulatory capacity accounts for increased incidence of pain and disability in older adults. That endogenous pain modulation dysfunction is related to persistent pain is supported by a number of studies comparing chronic pain patients with healthy controls using a "pain-inhibition-by-pain" experimental model. Although this research group (and others) has shown age deficiencies using the "pain inhibits pain" model, other human laboratory models that are known to engage pain modulatory systems have not been tested across the lifespan, each potentially involving different mechanisms. The overarching goal of the proposed research is to characterize age-related changes in pain inhibitory and facilitatory function and to investigate the biopsychosocial mediators and clinical relevance of these changes. Our preliminary data suggest that sophisticated psychophysical methods reflecting net inhibitory or facilitatory effects are sensitive to changes across the lifespan and will provide a more comprehensive and clinically-relevant picture of changes in pain processing associated with aging. This proposed study will enroll 180 human subjects, ages 18-79, who will undergo assessment during three pain modulatory sessions at baseline. The pain modulatory tests will include inhibitory protocols; diffuse noxious controls and offset analgesia, and tests that involve pain facilitation; temporal summation, impaired decay of subthreshold pain (proxy for central sensitization), and a prolonged protocol which we have found produces greater temporal sensitization across repeated trials in older subjects. Individualized temperatures for the contact heat test stimulus will be used so that subjects experience similar, moderate levels of pain. We hypothesize that age will be associated with poorer endogenous pain inhibition from pain inhibitory protocols and increased pain from protocols that facilitate pain. A range of biopsychosocial markers will be measured that we hypothesize will mediate the association between age and variability in pain modulation. These measures include psychosocial factors (catastrophizing, sleep, stress, and negative emotions) and biological markers (blood pressure, 2-endorphin, cortisol, and other hypothalamic-pituitary- adrenal and immune markers). After establishing individual levels of pain facilitation and pain inhibition, we will assess pain during daily life and the impact of pain on quality of life using a series of telephone interviews and novel real-time electronic data capture each month for 6 months. We expect that changes in our pain modulatory tests will account for observed age differences in pain frequency, more pain intensity, number of pain sites, and in quality of life.