PERIPHERAL AND CENTRAL SENSITIZATION AFTER ECCENTRIC MUSCLE EXERCISE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。疼痛调查使用诱发疼痛的方案和/或样本参与者自然发生的疼痛。实验诱发的疼痛的研究在其适用于自然发生的疼痛方面是有限的，因为实验诱发的疼痛更容易预测和控制，而没有相同的意义和情感后果。纤维肌痛综合征（FMS）患者表现出强直性伤害性冲动输入的证据，这至少部分地负责他们的痛觉过敏/异常性疼痛和中枢致敏。我们假设间歇性的炎症性疼痛有助于触发信号级联，从而增加这些患者的外周和中枢致敏性。其中一种可能的炎症发作与运动或用力引起的肌肉损伤有关。我们提出的解决炎症在FMS疼痛中的作用的方法是研究炎症介质和/或急性期反应物。我们将研究迟发性肌肉酸痛（DOMS）中的这些炎症标志物。偏心肌肉收缩可以可靠地诱发暂时性肌肉酸痛和疼痛，发生在迟发性肌肉酸痛方案后。此外，有令人信服的证据表明偏心肌收缩强度与随后的肌肉酸痛之间存在剂量-反应关系。我们计划在诱导迟发性肌肉酸痛之前和之后检查对热/机械刺激的中枢/外周敏化或脱敏性。此外，我们将测试经过验证的炎症标志物，这些标志物也参与疼痛信号传导，包括血浆和尿液中的急性期反应物（ESR， CRP, neopterin），细胞因子和其他炎症介质，如MARCKS（肉芽肿化富丙氨酸蛋白激酶C底物），以研究它们与FMS中枢致敏的密切关系。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Investigations of pain use protocols that induce pain and/or sample participants with naturally occurring pain. Research examining experimentally induced pain is limited in its applicability to naturally occurring pain because experimentally induced pain is more predictable and controllable without the same meaning and emotional consequences. Patients with fibromyalgia syndrome (FMS) show evidence of tonic nociceptive impulse input, which is at least partially responsible for their hyperalgesia/allodynia and central sensitization. We hypothesize that intermittent bouts of inflammatory pain are instrumental in triggering signal cascades that increase peripheral and central sensitization in these patients. One of these possible inflammatory bouts is related to muscle injury from activity or exertion. Our proposed method of addressing the role of inflammation for pain in FMS is to study inflammatory mediators and/or acute phase reactants. We will study these inflammatory markers in delayed-onset muscle soreness (DOMS). Eccentric muscle contractions can reliably induce temporary muscle soreness and pain that occur after the performance of the DOMS protocol. In addition, there is convincing evidence of a dose-response relationship between the intensity of the eccentric muscle contractions and subsequent muscle soreness. We plan to examine central/peripheral sensitization or desensitization to thermal/mechanical stimuli before and after DOMS has been induced. In addition, we will test well validated markers of inflammation, that are also known to be involved in pain signaling, including acute phase reactants (ESR, CRP, neopterin), cytokines, and other inflammatory mediators like MARCKS (myristolated alanine rich protein kinase C substrate) in plasma and urine to investigate their close relationship with central sensitization in FMS.