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，包括感官，情感和认知成分。虽然很多 在开发啮齿动物模型的感觉和情感疼痛组成部分方面已付出了努力，较少已知 关于代表疼痛的认知成分的模型。研究认知的重要性 疼痛的成分是2倍：1-认知成分的某些特征，例如冲动性，有助于 由慢性疼痛状况引起的精神病合并症； 2-冲动是重要的贡献 开发物质使用障碍的因素。检查揭示疼痛模型的疼痛模型至关重要 由慢性疼痛和 opioid镇痛药。此外，将女性纳入检查疼痛引起的冲动性特别重要 由于女性在慢性疼痛状态期间更容易发展各种合并症。此应用程序 引入了延迟折现任务（DDT），作为疼痛认知成分的啮齿动物模型。 DDT有 被用来在精神病和药物使用模型中证明决策和冲动性的定义 啮齿动物和人类的条件。我们的初步发现表明男性和雌性大鼠接受治疗 后爪完全自由的辅助（CFA）引起的炎症性疼痛暴露延迟折现（即冲动） 这被吗啡阻塞。疼痛引起的冲动性是性二态性的，因为女性表现出更强 比男性打折。超过三个目标，该提案将研究性腺恐怖剂，VTA MU-Apoid受体和伏隔核D2受体对CFA诱导的冲动性的作用。这项研究是第一步 在检查疼痛引起的冲动性及其潜在机制的啮齿动物模型时。来自 拟议的研究将提高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有关。