Pain-induced impulsivity in rats and its mechanisms

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Pain is a complex subjective process consisting of sensory, affective and cognitive components. Although much effort has been made in developing rodent models for sensory and affective pain components, less is known about models that represent the cognitive component of pain. The importance of studying the cognitive component of pain is 2-fold: 1- certain features of the cognitive component, such as impulsivity, contribute to psychiatric comorbidities that result from chronic pain conditions; and 2- impulsivity is a significant contributing factor for the development of substance use disorders. It is critical to examine pain models that shed light on the mechanisms and etiology of psychiatric and substance abuse comorbidities stemming from chronic pain and opioid analgesics. Moreover, inclusion of females in examining pain-induced impulsivity is particularly important as females are more prone in to develop various comorbidities during chronic pain states. This application introduces the delay discounting task (DDT) as a rodent model of the cognitive component of pain. The DDT has been used to demonstrate deficits in decision-making and impulsivity in models of psychiatric and substance use conditions in rodents and in humans. Our preliminary findings suggest that male and female rats treated with hind paw complete freund’s adjuvant (CFA)-induced inflammatory pain exhibit delay discounting (i.e. impulsivity) that is blocked by morphine. The pain-induced impulsivity is sexually dimorphic as females show stronger discounting than males. Over three aims, this proposal will examine the role of gonadal hormones, VTA mu-opioid receptors, and nucleus accumbens D2 receptor on CFA-induced impulsivity. This study is the first step in examining a rodent model of pain-induced impulsivity and its underlying mechanisms. Findings from the proposed studies will advance our understanding of the multifactorial nature of pain perception, as well as the mechanisms that contribute to complications and comorbidities often associated with chronic pain conditions.