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）：与颞下颌疾病相关的慢性肌肉疼痛的病理生理学仍然知之甚少。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。具体来说，我们提出外周兴奋性氨基酸（EAA）和神经激肽（NK）受体是诱导中枢三叉神经元神经塑性变化和肌肉痛觉过敏发展的关键成分。为了研究我们的建议，构建了两个研究目标，每个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学方法来检验这些假设。在目标 1 中，我们将研究外周 EAA 受体对中枢敏化和肌肉痛觉过敏产生的贡献。该目标下的具体假设是 (1) 外周 NMDA 和非 NMDA 谷氨酸受体的阻断对实验性肌炎条件下 Vc 中的神经元激活有不同的影响，(2) 肌内注射谷氨酸将诱导 Vc 神经元的中枢敏化并拮抗外周 EAA 受体-将防止谷氨酸诱导的敏化，(3) 阻断外周 EAA 受体将显着减轻肌肉疼痛和实验性肌炎后的痛觉过敏。在目标 2 中，我们将研究 (a) 外周神经激肽受体对中枢敏化和肌肉痛觉过敏产生的贡献，以及 (b) 外周 EAA 和 NK 受体在肌肉痛觉过敏产生中的相互作用。具体假设是(4)NK1或NK2受体的阻断将不同地影响Vc中炎症诱导的神经元激活，(5)用NK1或NK2受体拮抗剂的局部治疗将阻止炎症诱导的Vc神经元的敏化，(6)阻断外周NK1或NK2受体的阻断将显着减轻炎症诱发的肌肉痛觉过敏，(7)同时阻断外周EAA和NK受体将减轻炎症诱发的肌肉痛觉过敏。 Vc 中的 c-fos 表达大于仅阻断每种受体类型所产生的表达，并且 (8) 阻断外周 EAA 和 NK 受体将比仅阻断每种受体类型所产生的肌肉痛觉过敏减少更大。这些研究将有助于了解慢性口面部肌肉疼痛的病理生理学，并为新治疗方式的开发提供直接见解。