Both psychological and physiological factors contribute to individual differences in nociception. The current proposal examines the effects of stress and social support on nociception and the physiological mechanisms through which these psychological constructs influence nociceptive behavior. We will use a spared nerve injury model in mice to 1) define the parameters under which stress affects nociception, 2) to evaluate the importance of hormonal and inflammatory responses in mediating stress-induced increases in allodynia, 3) to determine the physiological mechanisms through which social interaction decreases allodynia, and 4) determine whether social interaction can mitigate the effects of stress on nociception. The overall hypothesis is that stress will decrease, and social interaction will increase, nociceptive thresholds through a mechanism that involves altered corticosteroid exposure. The data collected as part of this proposal will increase our understanding of the how psychological variables, such as stress and social support, affect nociceptive thresholds. Ultimately, a better understanding of the pathogenesis of neuropathic pain could facilitate the development of therapeutic approaches for the prevention and treatment of pain-related syndromes in humans and other animals. PUBLIC HEALTH RELEVANCE Pain serves a very important, adaptive, function of increasing awareness of noxious stimuli as a means of preventing or limiting tissue damage, however, when pain becomes intractable or is elicited by typically innocuous stimuli, then it becomes debilitating to the individual and negatively impacts quality of life. The overarching goal of this proposal is to provide insights into the physiological mechanisms underlying psychosocial influences on pain, in hopes of better understanding the factors that contribute to individual differences in the development and expression pain behaviors. Improved understanding of the physiological mechanisms underlying pain behavior is expected to lead to improved treatment of pain in humans.