Immune and Gilia Regulation of Pain & Analgesic Actions

PI的临床研究计划试图了解外周免疫细胞的激活和 中枢神经系统胶质细胞(小胶质细胞和星形胶质细胞)触发一系列事件，导致神经元 止痛药的临床相关作用的激活、病理性疼痛状态和失调。 目前的研究重点与她理解(A)免疫-神经双向-免疫的长期目标直接相关。 定向相互作用，以及(B)疼痛调制系统。 拟议的项目是申请K05奖，以使PI专注于方案调查 病理性疼痛状态。目前获得资助的项目包括：(A)免疫/神经胶质调节 疼痛状态；NIDA K02(Watkins Pi；6/03-5/08；DA015642)；(B)通过脊髓白介素10基因进行疼痛控制 治疗；NIDA CEBRA II期(R01；Milligan Pi；Watkins Copi；09/04-09/09；DA018156)；(C)疼痛 通过神经元到胶质细胞信号转导促进；NIDA R01(Watkins PI；3/05-12/09；DA017670)；(D)阿片类药物 止痛药：三叉神经和脊髓神经胶质激活的调节；NIDCR R01(Watkins PI；7/06-4/11； (E)探索血脑屏障通透性胶质细胞激活抑制剂AV411；Avigen (Watkins Pl；1/06-12/08)；(F)建立大鼠模型以评估偏头痛中潜在的神经胶质细胞参与； 葛兰素史克(Watkins Pi；1/07-12/09)；(G)从大鼠到人的翻译：慢性疼痛状态 人类与脊髓和/或脑内神经胶质细胞的激活有关？；美国纤维肌痛综合征 协会(Watkins CD Boulder Pi；不限成员名额小额赠款)；(H)人脊髓神经胶质细胞因子& 慢性疼痛NIAMSD R01(Lorton，Pi；Watkins，Copi；7/07-6/12；AR054647)；&(I)信使核糖核酸和蛋白质分析 有慢性疼痛和无慢性疼痛的脊髓损伤患者的脊髓和脑脊液 治疗和康复医院(Watkins CU Boulder Pi；9/07-不限成员名额小额赠款)。此外, 正在审查的项目包括：(J)开发不能激活胶质细胞的阿片类药物治疗方法； Covidien(Watkins Pi)；(K)探索神经胶质细胞调节临床相关阿片类药物活动的潜力，R01 建议(Watkins PI)；和(I)利用病毒模仿开发治疗神经病理性疼痛的新疗法， R21提案(Leinwand Pi；Watkins Copi)。因此，这是一个积极而多样的研究方案，探索 处于疼痛研究前沿的多层次分析。所有这些项目都集中在 了解疼痛的免疫/神经胶质调节和止痛作用。除了这项广泛的研究 计划，国际和平协会致力于通过审查对科学界和非科学界人士进行有关这些主题的教育 文章和章节和特邀演讲，以及年轻调查人员的指导。

The Pi'spreclinical research program seeks to understand how activation of peripheral immune cells and central nervous system glia (microglia and astrocytes) triggers a cascade of events leading to neuronal activation, pathological pain states, and dysregulation of the clinically relevant effects of analgesic drugs. The current research focus is directly relevant to her long-term goals of understanding (a) immune-neural bi- directional interactions, and (b) pain modulation systems. The proposed project is a request for a K05 award for the PI to focus on programmatic investigations of pathological pain states. The currently funded projects include: (a) Immune/glial mediation of exaggerated pain states; NIDA K02 (Watkins PI; 6/03-5/08; DA015642); (b) Pain control via spinal interleukin-10 gene therapy; NIDA CEBRA Phase II (R01; Milligan PI; Watkins coPI; 09/04- 09/09; DA018156); (c) Pain facilitation via neuron-to-glia signaling; NIDA R01 (Watkins PI; 3/05-12/09; DA017670); (d) Opioid analgesics: modulation.of trigeminal & spinal glial activation; NIDCR R01 (Watkins PI; 7/06-4/11; DE017782); (e) Exploration of AV411, a blood brain barrier permeable glial activation inhibitor; Avigen (Watkins Pl;1/06-12/08); (f) Development of rat models to assess potential glial involvement in migraine; GlaxoSmithKline (Watkins PI; 1/07-12/09); (g) Translation from rats to humans: are chronic pain states in humans associated with glial activation in spinal cord and/or brain?; American Fibromyalgia Syndrome Association (Watkins CD Boulder PI; open ended small grant); (h) Human spinal cord glial cytokines & chronic pain NIAMSD R01 (Lorton, PI; Watkins, coPI; 7/07-6/12; AR054647); & (i) mRNA & protein analyses of spinal cord & CSF from spinal cord injury patients with vs without chronic pain; Craig Spinal Cord Injury Treatment & Rehabilitation Hospital (Watkins CU Boulder PI; 9/07-open ended small grant). In addition, projects under review include: (j) Development of opioid therapeutic approaches that fail to activate glia; Covidien (Watkins PI);(k) Exploring the potential of glia for regulating clinically relevant opioid actions, R01 proposal (Watkins PI);and (I) Exploiting viral mimicry to develop new therapies for treating neuropathic pain, R21 proposal (Leinwand PI; Watkins coPI). Thus this is an active & diverse research program exploring multiple levels of analyses at the forefront of pain research. All of these projects are focused on understanding immune/glial regulation of pain and analgesic actions. Beyond this extensive research program, the PI is committed to education of the scientific and lay communities on these topics via review articles and chapters and invited talks, and the mentorship of young investigators.