NEUROBIOLOGY OF ANOREXIA INDUCED BY MIGRAINE PAIN

经历急性、短暂或持续性疼痛的患者经常报告完全或部分食欲不振。尽管其发病率很高，但疼痛引起的厌食行为的神经基础尚不清楚。这一建议的前提是疼痛和厌食症之间的联系，这在偏头痛发作时尤其明显。本研究的目的是利用我们的动物模型，对疼痛引起的厌食症的神经生物学有新的认识。本提案的具体目标源于我们正在进行的偏头痛病理生理学和颅内疼痛信号如何研究下丘脑的基础和临床研究。具体目标1将确定硬脑膜的刺激是否可以激活介导厌食症的大脑区域的神经元，我们将硬脑膜作为颅内疼痛（如偏头痛）的模型。特异性目的2将确定传递颅内疼痛信号到调节进食行为的下丘脑神经元的神经通路。Specific Aim 3将确定受硬脑膜刺激激活的神经元的化学表型，并确定它们是否表达最近被证明抑制食欲并在临床上用于对抗肥胖的分子（如CCK和瘦素）。特异性Aim 4a将确定在我们的动物模型中硬脑膜刺激是否可以抑制摄食行为，以及它是否类似于人类受试者偏头痛发作时的摄食行为抑制。具体目标4b将验证我们的工作假设，即颅内疼痛对摄食行为的抑制是由含有CCK的臂旁神经元和腹内侧下丘脑神经元的激活介导的，腹内侧下丘脑神经元表现出厌食性神经肽CCK和/或激素瘦素的受体。这项拨款提案提供了来自喂养行为领域和疼痛和偏头痛领域的专业知识的独特合作。这种跨学科的方法提供了一个机会，使用最先进的技术来检查神经解剖学，神经生理学，分子和行为方面的神经机制，使疼痛诱导厌食症；这是一种具有独特临床意义的生物学现象，影响着美国数百万的疼痛患者。

Patients who experience acute, transient or persistent pain often repor6t complete or partial loss of appetite. Despite its high prevalence, the neural basis of pain-induced anorexic behavior is unknown. The premise for this proposal is the association between pain and anorexia, which is particularly striking during attacks of migraine headache. The objectives of the current proposal are to gain novel understanding of the neurobiology of anorexia induced by pain using our animal model. The specific aims in this proposal have been born out of our ongoing basic and clinical studies on the pathophysiology of migraine and how intracranial pain signals research the hypothalamus. Specific Aim 1 will determine whether stimulus of the dura, which we use as a model for intracranial pain (such as migraine), can activate neurons in brain areas that mediate anorexia. Specific Aim 2 will identify the neural pathways that transmit intracranial pain signals to hypothalamic neurons that regulate feeding behavior. Specific Aim 3 will identify the chemical phenotype of the neurons activated by dural stimulation and determine whether they express molecules (such as CCK and leptin) that were shown recently to suppress appetite and used clinically to fight obesity. Specific Aim 4a will determine whether dural stimulation can suppress feeding behavior in our animal model and whether it resembles the suppression of feeding behavior during migraine attack in human subjects. Specific aim 4b will test our working hypothesis that the suppression of feeding behavior by intracranial pain is mediated by activation of parabrachial neurons that contain CCK and ventromedial hypothalamic neurons that exhibit receptors to anorexic neuropeptide CCK and/or the hormone leptin. This grant proposal offers a unique collaborative effort of expertise from the field of feeding behavior and the field of pain and migraine. This interdisciplinary approach provides an opportunity to use state-of-the-art techniques to examine neuroanatomical, neurophysiological, molecular, and behavioral aspects of the neural mechanism that enables pain to induce anorexia; a biological phenomenon of distinct clinical relevance that affects millions of pain patients in the US.