NEUROPHYSIOLOGY OF CRANIAL HEADACHE

描述(改编自申请人的摘要) 伴随着颅内病变的头痛以及 偏头痛的头痛被认为是机械性的或 化学诱导感觉神经纤维的激活或敏化 在颅内脑膜中。然而，进一步了解 头痛的机制受到以下方面信息的缺乏的限制 脑膜感觉纤维的反应特性。长期目标 这项研究的目的是确定刺激的类型和生理 刺激脑膜初级传入神经元和 研究它们兴奋的药理机制 被压制。提出了五个具体的目标来审查这些回应 软脑膜和硬脑膜传入。具体目标1将描述 供血感觉神经传入的生理反应特性 大脑中动脉采用分级机械和化学刺激。 具体目标2将确定颅内升高的影响 压力和炎症对脑膜反应特性的影响 支配硬脑膜静脉窦和大脑中段的传入 动脉。具体目标3将确定5HT1b/D激动剂的效果 关于机械和化学诱导的致敏脑膜传入。 特定目标4将确定选择性钙通道的作用 机械致敏和化学致敏脑膜的阻滞剂 传入器。具体目标5将确定急性扩散的影响 机械和化学致敏脑膜的抑制作用 传入器。

Description (adapted from applicant's abstract) Headaches that accompany intracranial pathologies as well as the headache of migraine are thought to result from mechanically or chemically induced activation or sensitization of sensory nerve fibers in the intracranial meninges. However, further understanding of the mechanisms of headaches is limited by the lack of information regarding the response properties of meningeal sensory fibers. The long-term goal of this research is to identify the types of stimuli and physiological conditions that excite meningeal primary afferent neurons and to investigate the pharmacological mechanisms by which their excitation may be suppressed. Five Specific Aims are proposed to examine the responses of both pial and dural afferents. Specific Aim 1 will characterize the physiological response properties of sensory afferents supplying the middle cerebral artery using graded mechanical and chemical stimuli. Specific Aim 2 will determine the effects of increased intracranial pressure and inflammation on the response properties of meningeal afferents that innervate the dural venous sinuses and middle cerebral artery. Specific Aim 3 will determine the effects of 5HT1B/D agonists on mechanical- and chemical-induced sensitized meningeal afferents. Specific Aim 4 will determine the effects of selective calcium channel blockers on mechanical- and chemical-induced sensitized meningeal afferents. Specific Aim 5 will determine the effects of acute spreading depression on mechanical- and chemical-induced sensitized meningeal afferents.