Brain reward circuits and relief of ongoing pain

大脑奖励回路和缓解持续疼痛

基本信息

批准号：
8431853
负责人：
Frank Porreca
金额：
$ 56.79万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-01 至 2018-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8431853
关键词：
Absence of pain sensation Acute Acute Pain Affective Animals Anterior Behavioral Biological Markers Brain Cells Cognitive Data Dimensions Dopamine Functional Magnetic Resonance Imaging Human Image Injury Investigation Lesion Lidocaine Measurement Mediating Microdialysis Microinjections Modeling Molecular Target Morphine Nerve Block Nociception Nucleus Accumbens Opioid Pain Pathway interactions Patients Peripheral Nerves Pharmaceutical Preparations Postoperative Pain Rattus Rest Rewards Sensory Signal Transduction Speed Stimulus Surgical incisions Time Tyrosine 3-Monooxygenase Ventral Tegmental Area Work base chronic pain cingulate cortex dopaminergic neuron expectation experience extracellular human data in vivo injured motivated behavior neurochemistry pre-clinical pre-clinical research preference prevent public health relevance research study response reward processing transmission process

Absence of pain sensation Acute Acute Pain Affective Animals Anterior Behavioral Biological Markers Brain Cells Cognitive Data Dimensions Dopamine Functional Magnetic Resonance Imaging Human Image Injury Investigation Lesion Lidocaine Measurement Mediating Microdialysis Microinjections Modeling Molecular Target Morphine Nerve Block Nociception Nucleus Accumbens Opioid Pain Pathway interactions Patients Peripheral Nerves Pharmaceutical Preparations Postoperative Pain Rattus Rest Rewards Sensory Signal Transduction Speed Stimulus Surgical incisions Time Tyrosine 3-Monooxygenase Ventral Tegmental Area Work base chronic pain cingulate cortex dopaminergic neuron expectation experience extracellular human data in vivo injured motivated behavior neurochemistry pre-clinical pre-clinical research preference prevent public health relevance research study response reward processing transmission process

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项目摘要

DESCRIPTION (provided by applicant): Pain is a subjective, multi-dimensional experience with sensory, affective and cognitive components. The affective (aversive) dimensions of pain are the main complaint of patients. We have attempted to capture and mechanistically evaluate affective dimensions of ongoing pain in preclinical settings. The aversiveness of pain provides strong motivational drive to seek relief. Thus, treatments known to relieve pain clinically produce conditioned place preference selectively in injured animals, inferring activation of brain reward pathways. This possibility is consistent with human data that relief of pain is rewarding. In this application, we ask whether, and how, relief of ongoing pain might modulate brain reward circuits. Additionally, we explore whether manipulations that selectively target affective, rather than sensory, components of pain also activate reward circuits. We will use a rat model of time-dependent incisional pain to explore the potential activation of reward pathways by pain relief resulting from either peripheral nerve block (block of afferent input) or manipulations within the rostral anterior cingulate cortex (rACC, i.e., modulation of aversiveness without altering nociceptive input). We will use anatomical (IHC), neurochemical (in vivo microdialysis), behavioral and imaging (animal fMRI) analyses to characterize the functional activation of the nucleus accumbens (NAc)(Aim 1) and/or ventral tegmental area (VTA)(Aim 2) by pain relief or the expectation of relief. Functional connectivity between the rACC and the NAc that underlies motivated behavior to seek relief will be studied in Aim 3. Understanding circuits that reflect relief of ongoing pain will help to identify new molecular targets that may be exploited for discovery of therapies directly targeting affective dimensions of pain that may have increased translational relevance and ultimately validating a biomarker of pain relief (i.e., analgesia).

描述（由申请人提供）：疼痛是一种具有感官，情感和认知成分的主观多维体验。疼痛的情感（厌恶）维度是患者的主要抱怨。我们试图捕获和机械地评估临床前环境中持续疼痛的情感维度。疼痛的厌恶性为寻求救济提供了强烈的动力。因此，已知可以缓解疼痛的治疗临床产生在受伤的动物中有选择性地偏好，推断大脑奖励途径的激活。这种可能性与人类数据相一致，即缓解疼痛是有益的。在此应用中，我们询问持续疼痛的缓解以及如何减轻大脑奖励电路。此外，我们探讨了有选择地靶向情感而不是感觉的疼痛组成部分的操纵是否也激活了奖励电路。我们将使用与时间相关的切口疼痛的大鼠模型探索奖励途径的潜在激活，这是由外周神经阻止（传入输入的块）或鼻扣前扣带回皮层内的操作引起的疼痛的潜在激活（RACC，即不改变厌恶感的无厌食性，而无需抗厌食的调节）。我们将使用解剖学（IHC），神经化学（体内微透析），行为和成像（动物fMRI）分析来表征Accumbens（NAC）（AIM 1）（AIM 1）和/或腹部段落区域（AIM 2）的功能激活（AIM 2）（AIM 2）（aim 2）。 RACC与基于动机行为寻求救济的NAC之间的功能连通性将在AIM 3中进行研究。理解反映持续疼痛的电路将有助于确定可能利用直接针对靶向情感疼痛的疗法的新分子靶标的，这些疗法可能会增加相关性和疼痛的相关性并最终验证疼痛的疼痛（均为生物标志）的痛苦（即均为生物标志）。