Mechanisms of Social Support on Pain-Induced Affective Response

社会支持对疼痛引起的情感反应的机制

• 批准号: 8967904
• 负责人: RUIXIN ZHANG
• 金额: $ 23.03万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8967904
• 关键词: Acute Pain; Affect; Affective; Analgesics; Animals; Anterior; Area; Behavior; Behavioral; Boxing; Brain; Clinical Research; Cognitive; Data; Development; Dimensions; Dorsal; Electroacupuncture; Electrodes; Female; Formalin; Fostering; Freund' s Adjuvant; Functional Magnetic Resonance Imaging; Individual; Investigation; Knowledge; Lesion; Light; Link; Mechanical Stimulation; Microinjections; Modeling; Morphine; Naloxone; Nerve; Neuroglia; Neurons; Opioid; Pain; Pain intensity; Pain management; Partner in relationship; Peripheral; Persistent pain; Plexiglas; Plexiglass; Rattus; Rhodopsin; Role; Sensory; Site; Smell Perception; Social Interaction; Social support; Sorting - Cell Movement; Staging; Support Groups; Testing; Viral Vector; Visual; adeno-associated viral vector; attenuation; avoidance behavior; base; cingulate cortex; conditioning; excitatory neuron; inflammatory pain; injured; male; optical fiber; optogenetics; pain inhibition; preference; response; sex

 DESCRIPTION (provided by applicant): Pain contains sensory-discriminative, affective-motivational, and cognitive-evaluative dimensions. Animal studies demonstrate that social interaction/support inhibits the sensory dimension in acute pain models. However, it is yet to be demonstrated whether social interaction/support modulates the affective dimension. The objective of this proposal is to utilize a combination of behavioral, optogenetic and micro-wire array approaches to evaluate the effects and mechanisms of social support on the affective components of pain. Our preliminary data demonstrate that the presence of a cage mate during complete Freund adjuvant-induced pain- paired conditioning mitigated the avoidance response assessed with a conditioned place avoidance (CPA) test, indicating that social interaction/support alleviated the on-going pain and affective response. The data also showed that rostral anterior cingulated cortex (rACC) excitatory neuronal activity was enhanced during pain. Yellow light stimulation suppressed rACC excitatory neuronal activity and CPA in rats bearing the viral vector AAV5-CaMKIIa-eNpHR3.0-EYFP in the rACC. We hypothesize that social interaction/support alleviates affective response by inhibiting rACC neuronal activities. Aim I is to determine whether social interaction/support inhibits inflammatory pain-induced affective response. We hypothesize that a same- or opposite-sex cage mate-provided social interaction/support will inhibit pain-induced affective response and that untreated cage mates will show CPA. Aim II is to determine whether social interaction/support inhibits rACC excitatory neuronal activity. The rACC will be stimulated with blue or yellow light through optical fibers, an multi-channel electrodes will record neuronal activity during pre-conditioning test, conditioning and post- conditioning test in both CFA-injected and cage mate rats. Multiunit activities will be sorted to identify individual neuronal spike. We hypothesize that 1) social interaction/support wil significantly inhibit rACC excitatory neuronal activity in CFA-injected rats, 2) blue light stimulation of the hChR2-bearing rACC during pain-paired conditioning will counteract the effect of social interaction/support, and yellow light stimulation of the eNpHR3.0-bearing rACC will significantly inhibit affective pain, 3) cage mates will show enhanced rACC neuronal activity compared to baseline when in pain-paired box during both conditioning and post conditioning- test and, 4) blue light and yellow light stimulation during pain-paired conditioning will respectively facilitate and decrease CPA of cage mates compared to control. The findings will advance knowledge of the effects and mechanisms of a non-pharmacological therapy on persistent pain. RELEVANCE: Control and management of pain remain serious challenges. The findings of this proposed study will advance knowledge of the effects and mechanisms of a non-pharmacological therapy for pain.

 描述（由申请人提供）：疼痛包含感觉辨别、情感动机和认知评估维度。动物研究表明，社交互动/支持会抑制急性疼痛模型中的感觉维度。然而，尚未证明它是否与社交有关。该提案的目的是利用行为、光遗传学和微线阵列方法的组合来评估社会支持对疼痛情感成分的影响和机制。在完全弗氏佐剂诱导的疼痛配对调节过程中，笼中伴侣的存在减轻了条件性位置回避（CPA）测试评估的回避反应，表明社交互动/支持减轻了持续的疼痛和情感反应。还表明，在携带病毒载体的大鼠中，黄光刺激抑制了 rACC 兴奋性神经元活动和 CPA。 rACC 中的 AAV5-CaMKIIa-eNpHR3.0-EYFP 我们追求社交互动/支持通过抑制 rACC 神经活动来减轻情感反应。目标 I 是确定社交互动/支持是否抑制炎症性疼痛诱导的情感反应。或异性笼中伴侣提供的社交互动/支持将抑制疼痛引起的情感反应，而未经治疗的笼中伴侣将显示 CPA 目标 II 是确定是否社交。相互作用/支持抑制 rACC 兴奋性神经元活动 rACC 将通过光纤用蓝光或黄光刺激，多通道电极将记录 CFA 注射和后处理测试期间的神经元活动。笼中交配大鼠的多单位活动将被分类以识别个体神经尖峰，我们发现 1) 社交互动/支持将显着抑制注射 CFA 的大鼠的 rACC 兴奋性神经活动，2) 蓝色。在疼痛配对调节过程中，对带有 hChR2 的 rACC 进行光刺激将抵消社交互动/支持的影响，对带有 eNpHR3.0 的 rACC 进行黄光刺激将显着抑制情感疼痛，3）笼中伙伴将表现出增强的 rACC 神经元与基线相比，在调节和后调节测试期间在疼痛配对盒中的活动，4) 在疼痛配对调节期间蓝光和黄光刺激将分别促进和降低笼中伙伴的 CPA与对照相比，这些发现将增进对非药物疗法对持续性疼痛的影响和机制的了解。 相关性：疼痛的控制和管理仍然是严峻的挑战，这项研究的结果将增进对非药物治疗疼痛的作用和机制的了解。