Pain-induced impulsivity in rats and its mechanisms

疼痛诱发大鼠冲动及其机制

• 批准号: 10359932
• 负责人: Arbi Nazarian
• 金额: $ 42.9万
• 依托单位: WESTERN UNIVERSITY OF HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10359932
• 关键词: Address; Affective; Brain; Castration; Chronic inflammatory pain; Cognitive; Complex; Decision Making; Depreciation; Development; Dopamine; Dopamine D2 Receptor; Dopamine Receptor; Emotional; Estradiol; Etiology; Exhibits; Female; Freund' s Adjuvant; Gonadal Hormones; Hormone Receptor; Hormones; Human; Impulsivity; Lentivirus Vector; Light; Link; Measures; Mediating; Modeling; Morphine; Nucleus Accumbens; Operant Conditioning; Opioid Analgesics; Opioid Antagonist; Opioid Peptide; Opioid Receptor; Opioid agonist; Ovariectomy; Pain; Pain Nature; Pathway interactions; Play; Procedures; Process; Progesterone; Rattus; Rewards; Rodent; Rodent Model; Role; Sensory; Stimulus; Substance Use Disorder; Substance abuse problem; System; Testosterone; Time; Tyrosine 3-Monooxygenase; Ventral Tegmental Area; adeno-associated viral vector; antagonist; behavior measurement; chronic pain; chronic pain patient; chronic painful condition; comorbidity; discounting; endogenous opioids; experience; gamma-Aminobutyric Acid; inflammatory pain; knock-down; male; mesolimbic system; mu opioid receptors; neurochemistry; opioid epidemic; opioid use; pain model; pain perception; prevent; psychiatric comorbidity; relating to nervous system; sexual dimorphism; small hairpin RNA; stem; substance use

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.

疼痛是一个复杂的主观过程，由感觉、情感和认知三部分组成。虽然很多 在发展感觉性和情感性疼痛成分的啮齿动物模型方面已经做出了努力，但知之甚少 关于代表疼痛认知成分的模型。研究认知能力的重要性 疼痛的成分有2个方面：1-认知成分的某些特征，如冲动，有助于 慢性疼痛引起的精神合并症；2-冲动是一个重要因素 物质使用障碍的发展因素。检查疼痛模型是至关重要的，它揭示了 慢性疼痛引起精神和物质滥用共病的机制和病因 阿片类镇痛剂。此外，将女性纳入检查疼痛诱发的冲动尤其重要 因为女性在慢性疼痛状态下更容易患上各种合并症。此应用程序 引入延迟折扣任务(DDT)作为疼痛认知成分的啮齿动物模型。滴滴涕有 在精神病学和药物使用模型中被用来证明决策缺陷和冲动 啮齿动物和人类的情况。我们的初步发现表明，无论是雄性还是雌性大鼠， 后爪完全弗氏佐剂(CFA)诱导的炎性疼痛表现出延迟折扣(即冲动性) 这是被吗啡阻断的。当女性表现出更强的性欲时，由疼痛引起的冲动是两面性的。 比男性打折。通过三个目标，这项建议将检验性激素、VTA类阿片受体和伏隔核D2受体在CFA诱导的冲动中的作用。这项研究是第一步 研究疼痛诱发冲动的啮齿动物模型及其潜在机制。研究结果： 拟议的研究将促进我们对疼痛感知的多因素性质的理解，以及 导致并发症和合并症的机制，通常与慢性疼痛状况有关。