Brain reward circuits and relief of ongoing pain

描述（由申请人提供）：疼痛是一种主观的、多维度的体验，包含感觉、情感和认知成分。疼痛的情感（厌恶）维度是患者的主要主诉。我们试图捕捉和机械地评估在临床前设置持续疼痛的情感维度。对痛苦的厌恶提供了强烈的寻求解脱的动机。因此，临床已知的缓解疼痛的治疗方法产生

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).