PRIMARY C NOCICEPTORS AND C SYMPATHETICS IN CRPS

CRPS 中的主要 C 伤害感受器和 C 交感神经

• 批准号: 7450871
• 负责人: JOSE L OCHOA
• 金额: $ 38.34万
• 依托单位: LEGACY EMANUEL HOSPITAL AND HEALTH CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-15 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7450871
• 关键词: Accounting; Action Potentials; Adrenergic Fibers; Axon; Behavior; C Fiber; Calcium; Causalgia; Clinical; Clinical Research; Complement; Complex Regional Pain Syndromes; Cutaneous; Depth; Diagnosis; Ectopic Expression; Excision; Human; Hyperalgesia; In Vitro; Investigation; Ion Channel; Knowledge; Local Anesthetics; Measures; Mechanics; Membrane; Menthol; Methods; Molecular; Molecular Biology; Muscle; Nature; Nerve; Nerve Fibers; Nerve Pain; Neurons; Neuropathy; Nociceptors; Norepinephrine; Organ Donor; Pain; Pain Origin; Pathogenesis; Pathology; Patients; Pattern; Peripheral; Peripheral Nerves; Potassium; Property; Protocols documentation; Psychophysiology; Rate; Recording of previous events; Recovery; Reflex Sympathetic Dystrophy; Research; Research Personnel; Role; Sampling; Sensory; Sensory Nerve Endings; Signal Transduction; Site; Skin; Sodium; Source; Spinal Cord; Stimulus; Structure; Symptoms; Syndrome; System; TPO gene; Tandem Pore Domain Potassium Channels; Testing; Thermal Hyperalgesias; Tissues; Week; allodynia; awake; base; central sensitization; chronic neuropathic pain; cinnamic aldehyde; cold temperature; in vivo; neuromechanism; neuronal cell body; neurophysiology; pain receptor; painful neuropathy; patch clamp; receptor; research study; response; spontaneous pain; voltage; volunteer

DESCRIPTION (provided by applicant): Chronic neuropathic pains and hyperalgesias/allodynias following peripheral nerve or tissue insults, whether associated with nerve pathology (CRPS II) or not (CRPS I), curse patients, elude therapies and puzzle researchers. Hyperfunction of peripheral pain receptors (nociceptors) is an accepted cause of abnormal painful input in neuropathy (CRPSII) and a hypothetical source of secondary upheaval of pain-signaling neurons in the spinal cord, in CRPS I. Either peripheral or central mechanisms might account for spontaneous pains and for mechanical and thermal hyperalgesias/allodynias. Abnormal interaction between peripheral sympathetic and nociceptor neurons, in skin or muscle, also remains a theoretical mechanism of neuropathic pain and hyperalgesias. Over the past three decades our group has regularly contributed factual scientific knowledge about fine structure, pathology, and normal and abnormal sensory function of nociceptors and efferent function of sympathetic units, in patients and volunteers. We remain engaged in clinical and research studies on neuropathic pains and recently developed robust methods that allow direct and simultaneous functional and biophysical characterization and testing of multiple subtypes of nociceptors, thermal (cold) receptors and sympathetic units, while observing possible nerve fiber interactions. This is achieved through microneurography and automated latency tracking (Qtrac) in awake humans. These approaches, complemented by in vitro studies on DRG neuron somata from CRPS patients, will be used to test 3 hypotheses for the origin of pain in CRPS: 1) Irritable primary nociceptor neurons, of different subtypes, evoke spontaneous pains and hyperalgesias/allodynias in CRPS patients via ectopic nerve impulse activity, caused by abnormal behavior of particular ion channels in nociceptor membranes. 2) Sympathetic efferent discharge, acting at axonal and/or soma sites, may increase primary cutaneous or deep tissue nociceptor activity in CRPS, thus generating pains. 3) Cold hyperalgesia/allodynia, a prominent symptom in CRPS, is due to (a) sensitization of specific noxious low- temperature membrane receptors in nociceptor afferents, (b) ectopic expression of non-noxious cooling receptors in nociceptor afferents, (c) central release of noxious cold-signaling input, or (d) secondary central sensitization. Results of this project will prove, or question, pertinent hypothetical mechanisms of neuropathic pains and will facilitate mechanism-targeted therapy, while protecting CRPS patients from iatrogenic harm.

描述(申请人提供)：周围神经或组织损伤后的慢性神经病理性疼痛和痛觉过敏/痛觉异常，无论是否与神经病理有关(CRPS II)(CRPS I)，诅咒患者，逃避治疗和困惑研究人员。外周痛觉受体(伤害性感受器)功能亢进是公认的神经病疼痛输入异常(CRPSII)的原因，也是CRPSI中脊髓痛信号神经元继发性隆起的假说来源。外周或中枢机制可能解释自发性疼痛以及机械性和热性痛觉过敏/痛觉异常。外周交感神经元和伤害性感受器神经元之间的异常相互作用，在皮肤或肌肉中，也是神经病理性疼痛和痛觉过敏的理论机制。在过去的三十年里，我们小组定期在患者和志愿者中提供关于伤害性感受器的精细结构、病理、正常和异常感觉功能以及交感单位的传出功能的事实科学知识。我们一直致力于神经性疼痛的临床和研究研究，最近开发出强大的方法，允许直接和同时进行伤害性感受器、热(冷)感受器和交感单位的多种亚型的功能和生物物理表征和测试，同时观察可能的神经纤维相互作用。这是通过清醒人类的显微神经学和自动潜伏期跟踪(QTrac)实现的。这些方法加上对CRPS患者DRG神经元胞体的体外研究，将被用于检验CRPS疼痛起源的3个假说：1)不同亚型的易激初级伤害性感受器神经元，通过异位神经冲动活动引起CRPS患者的自发性疼痛和痛觉过敏/痛觉异常，这是由伤害性感受器膜上特定离子通道的异常行为引起的。2)作用于轴突和/或胞体部位的交感传出放电可增加CRPS的初级皮肤或深层组织伤害性感受器活动，从而产生疼痛。3)冷痛敏/超敏是CRPS的一个显著症状，其原因是：(A)伤害性传入的特定低温膜受体敏化，(B)非伤害性冷却受体在伤害性传入中的异位表达，(C)伤害性冷信号输入的中枢释放，或(D)继发性的中枢敏化。该项目的结果将证明或质疑神经病理性疼痛的相关假设机制，并将促进机制靶向治疗，同时保护CRPS患者免受医源性伤害。