Neurochemistry of Pain: Measuring glutamatergic brain activity in response to p

描述(申请人提供)：据估计，美国约有5000万人遭受持续的、严重的疼痛。对疼痛的反应既涉及外周机制，也涉及中枢机制，多个系统、神经递质和受体在疼痛传递和反应中发挥作用。支持将疼痛感知为不愉快刺激体验的神经结构与支持负面情绪体验的神经结构强烈重叠，这些区域被认为参与了成瘾后启动寻求药物行为的最终共同途径。对损伤或疾病的急性疼痛是如何转变为慢性疼痛综合征的，以及疼痛的潜在神经生物学仍然知之甚少。该项目建议通过将神经激活的变化与神经递质谷氨酸及其中间体谷氨酰胺对疼痛的反应浓度的变化联系起来，扩展使用功能磁共振波谱(FMRS)在疼痛中的先前发现。我们假设：1)对健康人施加疼痛刺激将增加与疼痛感知相关的大脑区域的中枢神经元活动和谷氨酸能神经传递，2)用1H-MRS测量的谷氨酰胺水平将反映活动和谷氨酸能传递的相对水平，3)痛阈值将与负面情绪和躯体主诉的报告负相关，而谷氨酸和谷氨酰胺对痛苦刺激的反应将与这些指标正相关。测量这种激活和神经递质增加的能力将为疼痛综合征的分类提供一个新的替代标记。这种对疼痛潜在的中枢神经化学反应的研究，以及开发一种精确测量这些反应的技术，将具有超越更好地理解疼痛和改进疼痛治疗的影响，甚至可能影响到与止痛药成瘾这一重要的相关问题。

DESCRIPTION (provided by applicant): It is estimated that about 50 million people in the United States suffer from persistent, serious pain. Response to pain involves both peripheral and central mechanisms with several systems, neurotransmitters and receptors playing a role in pain transmission and response. The neural structures supporting the perception of pain as experience of an unpleasant stimulus strongly overlap with those that support the experience of negative emotion and those areas proposed to be involved in a final common pathway for initiation of drug seeking behaviors in addiction. How acute pain in response to an injury or disease transitions to a chronic pain syndrome, and the underlying neurobiology of pain are still poorly understood. This project proposes to extend previous findings using functional Magnetic Resonance Spectroscopy (fMRS) in pain by linking changes in neural activation to changes in concentration of the neurotransmitter glutamate and one of it's intermediates, glutamine, in response to pain. We hypothesize 1) that painful stimuli administered to healthy humans will increase central neuronal activity and glutamatergic neurotransmission in regions of the brain associated with pain perception, 2) Glutamine levels measured with 1H-MRS will reflect relative levels of activity and glutamatergic transmission and 3) Pain thresholds will be negatively correlated with reports of negative emotion and somatic complaints, while glutamate and glutamine responses to a painful stimulus will be positively correlated with these same measures. The ability to measure such activation and neurotransmitter increases will provide a novel surrogate marker for categorizing pain syndromes. Such investigations of the underlying central neurochemical responses to pain and the development of a technique to precisely measure these responses will have implications extending beyond a better understanding of pain and improving pain treatment and may even impact on the important related issue of addiction to analgesics.