Peripheral Receptor Mechanisms in Orofacial Muscle Pain

口面部肌肉疼痛的外周受体机制

• 批准号: 7161357
• 负责人: JIN Y Ro
• 金额: $ 34.15万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7161357
• 关键词: Acute; Affect; Area; Behavior; Behavioral; Behavioral Model; Chemicals; Chronic; Class; Classification; Clinical; Condition; D Aspartate; Development; Disease; Electrophysiology (science); Etiology; Excitatory Amino Acid Receptors; Excitatory Amino Acids; FOS gene; Functional disorder; Generations; Glutamate Receptor; Glutamates; Health; Hyperalgesia; Inflammation; Intramuscular Injections; Investigation; Maintenance; Masseter Muscle; Measures; Mediating; Mediator of activation protein; Modality; Modeling; Muscle; Muscle Development; Myalgia; Myositis; N-Methylaspartate; Neurons; Nociception; Nociceptors; Numbers; Pain; Peripheral; Population; Principal Investigator; Process; Property; Proteins; Rattus; Relative (related person); Research; Role; Signal Transduction; System; TAC1 gene; Techniques; Testing; Trigeminal System; Work; behavioral pharmacology; central sensitization; clinically significant; craniofacial; dorsal horn; extracellular; immunoreactivity; indexing; insight; interdisciplinary approach; interest; novel; orofacial; prevent; programs; receptor; research study

DESCRIPTION (provided by applicant): The pathophysiology of chronic muscle pain associated with temporomanibular disorders is still poorly understood. This research will elucidate the importance of peripheral receptor mechanisms in craniofacial muscle pain and hyperalgesia. Specifically, we propose that peripheral excitatory amino acid (EAA) and neurokinin (NK) receptors are critical components in inducing neuroplastic changes in central trigeminal neurons and the development of muscle hyperalgesia. To investigate our proposal, two research aims are constructed, each with several working hypotheses. We will use behavioral, immunocytochemical and electrophysiological approaches to test these hypotheses. In Aim 1, we will study the contribution of peripheral EAA receptors for the generation of central sensitization and muscle hyperalgesia. Specific hypotheses under this Aim are (1) Blockade of peripheral NMDA and non-NMDA glutamate receptors differentially affect neuronal activation in the Vc under an experimental myositis condition, (2) Intramuscular injections with glutamate will induce central sensitization ofVc neurons and antagonizing peripheral EAA receptors-will prevent the glutamate-induced sensitization, (3) Blockade of peripheral EAA receptors will significantly reduce muscle pain and hyperalgesia following experimental myositis. In Aim 2, we will study (a) the contribution of peripheral neurokinin receptors for the generation of central sensitization and muscle hyperalgesia, and (b) the interaction between peripheral EAA and NK receptors in generation of muscle hyperalgesia. Specific hypotheses are (4) Blockade ofNKl or NK2 receptor will differentially affect the inflammation^inducedneuronal activation in the Vc, (5) Local treatment with NK1 or NK2 receptor antagonist will prevent the, inflammation-induced sensitization of Vc neurons, (6) Blockade of peripheral NKl or NK2 receptor will significantly reduce the inflammation-induced muscle hyperalgesia, (7) Blockade of both peripheral EAA and NK receptors will reduce the inflammation-induced c-fos expression in the Vc greater than that produced by the blockade of each receptor type only, and (8) Blockade of both peripheral EAA and NK receptors will reduce the muscle hyperalgesia greater than that produced by the blockade of each receptor type only. These studies will contribute to understanding the pathophysiology of chronic orofacial muscle pain and provide direct insights for the development of new treatment modalities.

描述（由申请人提供）：与颞隐亚症相关的慢性肌肉疼痛的病理生理仍然知之甚少。这项研究将阐明外周受体机制在颅面肌肉疼痛和痛觉过敏中的重要性。具体而言，我们建议外周兴奋性氨基酸（EAA）和神经蛋白（NK）受体是诱导中央三叉神经元神经塑性变化和肌肉超敏过敏的发展的关键成分。为了调查我们的建议，建立了两个研究目标，每个研究目标都有几个工作假设。我们将使用行为，免疫细胞化学和电生理方法来检验这些假设。在AIM 1中，我们将研究外围EAA受体对中央敏化和肌肉超痛觉产生的贡献。 Specific hypotheses under this Aim are (1) Blockade of peripheral NMDA and non-NMDA glutamate receptors differentially affect neuronal activation in the Vc under an experimental myositis condition, (2) Intramuscular injections with glutamate will induce central sensitization ofVc neurons and antagonizing peripheral EAA receptors-will prevent the glutamate-induced sensitization, (3) Blockade实验性肌炎后，外周EAA受体的受体将显着减轻肌肉疼痛和痛觉过敏。在AIM 2中，我们将研究（a）周围神经激素受体对中央致敏和肌肉痛觉过敏的产生的贡献，以及（b）（b）周围EAA和NK受体在产生肌肉痛觉过敏中的相互作用。特定的假设是（4）NKL或NK2受体的阻滞会差异地影响VC中的炎症^诱导的神经元激活，（5）用NK1或NK2受体拮抗剂进行局部治疗，可以防止炎症诱导的VC神经元的炎症促使VC神经元的炎症，（6）炎症的障碍，（6）脑脉动脉络脉络脉络脉络nkl nkl或Nkl nkl nk2受到显着性脉动脉络脉络脉络脉络脉冲，这是NK2和NK2的脑中脉络脉络性脉动脉络性脉动脉络性脉动造成的效果。 （7）对外围EAA和NK受体的阻塞将减少VC中炎症诱导的C-FOS表达的比仅由每种受体类型的阻断所产生的表达更大，并且（8）阻断外周外EAA和NK受体的阻断将减少肌肉远和肌肉的肌肉差异，而肌肉均高于每种受体类型所产生的肌肉。这些研究将有助于理解慢性类似肌肉疼痛的病理生理学，并为发展新治疗方式提供直接见解。