Pain-induced impulsivity in rats and its mechanisms

疼痛诱发大鼠冲动及其机制

基本信息

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
项目类别：
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&apos 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

项目摘要

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、情感和认知成分组成。人们已经努力开发啮齿动物模型来了解感觉和情感疼痛成分，但鲜为人知关于代表疼痛认知成分的模型研究认知的重要性。疼痛的成分有两方面： 1- 认知成分的某些特征，例如冲动，有助于慢性疼痛引起的精神合并症；2- 冲动是一个重要的促成因素；研究揭示物质使用障碍发展的因素至关重要。慢性疼痛和药物滥用引起的精神和药物滥用合并症的机制和病因学此外，让女性参与检查疼痛引起的冲动尤为重要。因为女性在慢性疼痛状态下更容易出现各种合并症。引入延迟贴现任务（DDT）作为疼痛认知成分的啮齿动物模型。已被用来证明精神病学和药物滥用模型中的决策缺陷和冲动性我们的初步研究结果表明，对雄性和雌性大鼠进行了治疗。后爪完全弗氏佐剂 (CFA) 诱导的炎性疼痛表现出延迟贴现（即冲动性）吗啡可以阻断疼痛引起的冲动，雌性表现出更强的性冲动。该提案的三个目标是研究性腺激素、VTA mu-阿片受体和伏隔核 D2 受体对 CFA 诱导的冲动的作用。研究疼痛引起的冲动的啮齿动物模型及其潜在机制。拟议的研究将增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相关的并发症和合并症的机制。