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Dorsal horn circuits for mechanical allodynia

用于机械异常性疼痛的背角电路

基本信息

批准号：
10382342
负责人：
REBECCA P SEAL
金额：
$ 51.61万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-15 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10382342
关键词：
Acute Afferent Neurons Anatomy Applications Grants Behavior Behavioral Cells Cholecystokinin Clinical Development Disinhibition Electrophysiology (science)FOS gene Fiber Genetic Goals High Prevalence In Vitro Inflammatory Injury Interneurons Intrathecal Injections Mechanics Mediating Modeling Molecular Monitor Movement Nature Nerve Tissue Neurons Neuropathy Nociception Pain Persistent pain Population Posterior Horn Cells Process Rabies virus Role Slice Spinal Cord Synapses Techniques Testing Therapeutic Intervention Touch sensation Up-Regulation Work behavior test calretinin design dorsal horn effective therapy experimental study in vitro Model in vivo inflammatory pain integration site mechanical allodynia neural circuit neuromechanism novel novel therapeutic intervention pain model painful neuropathy postsynaptic protein kinase C gamma receptor somatosensory tool transmission process

项目摘要

Pain continues to be a major clinical problem due to its high prevalence and lack of adequate treatment options. The identification of more effective therapies is hampered by a lack of understanding of the neural circuits and mechanisms that underlie pain. Work outlined in this proposal is focused on delineating the dorsal horn circuits for mechanical allodynia, a common condition in which touch or movement become painful after injury. The dorsal horn is a major site for the integration of somatosensory information. It is also where injury- induced changes in the circuitry give rise to mechanical allodynia. In studies to elucidate the dorsal horn mechanical allodynia circuits, we have identified populations of dorsal horn excitatory interneurons that mediate this form of pain. Additionally, we present evidence supporting the concept that the neural circuitry that mediates mechanical allodynia in the dorsal horn differs depending on the nature of the injury. Thus, the overarching goal of this project is to delineate the dorsal horn circuits underlying mechanical allodynia in the context of the type of injury, inflammatory and neuropathic. In Aim 1) we will determine whether the populations of excitatory interneurons are required for mechanical allodynia produced by models of inflammatory and neuropathic pain. In Aim 2) we will expand our understanding of the dorsal horn circuitry related to these excitatory interneuron populations under naïve conditions by identifying the neurons monosynaptically connected to them. This more detailed picture of the basic dorsal horn circuitry will facilitate experiments aimed at identifying key changes that underlie mechanical allodynia caused by different types of injuries. In Aim 3) we will use an in vitro model of mechanical allodynia to test the role of these excitatory interneuron populations in inflammatory and neuropathic pain models. This will allow us to assess on a synaptic level the role of these neurons in mechanical allodynia in the context of injury-type. Classes of afferents and populations of lamina I projection neurons will also be assessed. These novel studies will provide a critical anatomical framework with which to advance molecular- and synaptic-level studies of the neurons and mechanisms that underlie mechanical allodynia as well as generate new therapeutic strategies.

由于其高患病率和缺乏适当的治疗，疼痛仍然是一个主要的临床问题