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，包括感觉，情感和认知成分。虽然大部分 尽管在开发用于感觉和情感疼痛成分的啮齿动物模型方面已经做出了努力，但所知甚少 关于疼痛的认知模型。研究认知的重要性 疼痛的组成部分是2倍：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共病; 2-冲动是一个重要的贡献 物质使用障碍的发展因素。研究疼痛模型至关重要， 慢性疼痛引起的精神和药物滥用共病的机制和病因， 阿片类镇痛药此外，将女性纳入检查疼痛引起的冲动是特别重要的 因为女性在慢性疼痛状态期间更容易发生各种合并症。本申请 介绍了延迟折扣任务（DDT）作为疼痛的认知成分的啮齿动物模型。DDT有 在精神病和物质使用模型中， 啮齿动物和人类的情况。我们的初步研究结果表明， 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） 被吗啡阻断疼痛引起的冲动是两性的，女性表现出更强的 比男性低。在三个目标，这项建议将检查性腺激素，腹侧被盖区μ阿片受体，和神经核D2受体对CFA诱导的冲动的作用。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。Findings from the 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 导致通常与慢性疼痛病症相关的并发症和共病的机制。