Green Light Therapy for Chronic Pain

绿光疗法治疗慢性疼痛

基本信息

批准号：
10180202
负责人：
Mohab M Ibrahim
金额：
$ 37.51万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-16 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10180202
关键词：
Abbreviations Absence of pain sensation Address Age Analgesics Animals Anti-Inflammatory Agents Area Astrocytes Brain Cannabis Capsaicin Centers for Disease Control and Prevention (U.S.)Cerebrospinal Fluid Clinic Clinical Clinical Trials Data Development Distal Drug Interactions Enkephalins Exposure to Glycoproteins HIV HIV Envelope Protein gp120 HIV Infections HIV antiretroviral HIV therapy HIV-1 Headache Health Highly Active Antiretroviral Therapy Human Hypersensitivity Immunosuppression Impairment Inflammation Mediators Inflammatory Lead Ligation Light Mechanics Mediating Migraine Modeling Motor Naloxone Nerve Growth Factors Neuropathy Opiate Addiction Opioid Opioid agonist Pain Pain management Patients Performance Peripheral Nervous System Diseases Pharmaceutical Preparations Pharmacological Treatment Phototherapy Plasma Play Predisposing Factor Preparation Principal Investigator Production Rattus Recombinants Reporting Research Research Personnel Reverse Transcriptase Inhibitors Role Safety Severities Smoke Spinal Cord Spinal cord posterior horn Spinal nerve structure System Testing Therapeutic Thermal Hyperalgesias Time Translating United States National Institutes of Health Viral Virus Diseases Visual Work analog antiretroviral therapy chronic neuropathic pain chronic pain chronic pain management chronic painful condition comorbidity cost cytokine endogenous opioids experimental study fibromyalgia pain fibromyalgia patients gabapentin improved innovation light intensity mu opioid receptors non-opioid analgesic novel nucleoside analog pain reduction painful neuropathy routine therapy sensory neuropathy side effect species difference visual performance

项目摘要

This application addresses the critical need for efficacious non-pharmacological treatments for human immunodeficiency virus type 1 (HIV) sensory neuropathy (HIV-SN). This neuropathy can be associated with viral infection alone, likely involving a role for the envelope glycoprotein gp120; or a drug-induced toxic neuropathy associated with the use of nucleoside analogue reverse transcriptase inhibitors (NRTIs) as a component of highly active anti-retroviral therapy. Dr. Mohab Ibrahim, Principal Investigator on this project, along with Dr. Rajesh Khanna, a co-Investigator on this project, first showed that low intensity green light provided long-lasting antinociception in naïve animals. No side-effects were noted and motor performance was not impaired. The antinociception may be due to increased endogenous opioid expression observed in the spinal cord and possibly the decrease in inflammatory factors. Their recent work also demonstrated reversal of mechanical and thermal hypersensitivity in rats subjected to spinal nerve ligation– a model of chronic neuropathic pain. Thus, understanding the mechanisms that contribute to green light mediated antinociception would be a critical first step in developing this as a novel form of therapy. We will test our hypothesis that exposure to green light will reduce thermal, mechanical hypersensitivity due to engagement of the endogenous opioid system and decrease inflammatory mediators. We will test this hypothesis with four related, but independent, specific aims using the envelope glycoprotein gp120 model of HIV-induced painful peripheral neuropathy. We will first determine the time-course and light intensity (lux levels) needed for reversal of thermal and mechanical hypersensitivity in the gp120 model of HIV-induced painful peripheral neuropathy and the mechanical hypersensitivity associated with antiretroviral therapy (SA1). Next, we will determine the contribution of the endogenous opioid system in mediating the effects of green light emitting diode (GLED) and whether a fixed light intensity/duration along with a mu opioid receptor agonist or a non opioid neuropathic pain medication such as gabapentin result in a synergistic antinociceptive effect in animals with gp120-induced neuropathy (SA2). We will characterize cellular activation and determine the levels of inflammatory cytokines in the spinal cord dorsal horn, brain, cerebrospinal fluid, and plasma from rats with gp120-induced neuropathy and following GLED exposure (SA3). Finally, we will investigate possible side effects that may be associated with prolonged exposure to green light therapy in preparation for introducing this therapy to human patients (SA4). Green light therapy resulting in decreased chronic pain without side effects has the promise of being easily translatable into the clinic due to their apparent efficacy, safety, low cost and availability. Our studies may offer an adjunct to current clinical therapies likely resulting in reducing opioids to manage HIV induced neuropathic pain, as well as other chronic pain states. Importantly, with a reduction in their pain, HIV patients may be more compliant with their antiretroviral therapy.

该申请解决了对人类有效非药物治疗的关键需求免疫缺陷病毒1型（HIV）感觉神经病（HIV-SN）。这种神经病可以与仅病毒感染，可能涉及包膜糖蛋白GP120的作用；或药物引起的有毒与使用核苷类模拟逆转录酶抑制剂（NRTI）相关的神经病该项目的首席研究员Mohab Ibrahim博士，与该项目的共同研究员Rajesh Khanna博士一起，首先表明低强度绿灯在幼稚的动物中提供了持久的抗伤害感受。没有注意到副作用，运动性能是不损害。抗伤害感受可能是由于内源性阿片类药物表达增加所致脊髓，可能会减少炎症因子。他们最近的工作也证明了受脊神经结扎的大鼠的机械和热超敏反应 - 一种慢性的模型神经性疼痛。这是理解有助于绿光介导的抗内核病患者的机制将其发展为一种新型的治疗形式，将是至关重要的第一步。我们将检验我们的假设暴露于绿光会因互动而减少热的机械性超敏反应内源性阿片类药物系统并减少炎症介质。我们将用四个相关但独立的特定目的使用艾滋病毒引起的痛苦的信封糖蛋白GP120模型周围神经病。我们将首先确定时间和光强度（lux级别） HIV引起的疼痛周围的GP120模型中的热和机械性超敏反应的逆转神经病和与抗逆转录病毒疗法相关的机械性超敏反应（SA1）。接下来，我们会的确定内源性阿片类药物在介导绿光发射作用中的贡献二极管（GLED）以及固定的光强度/持续时间以及MU阿片受体激动剂还是非卵毒素神经性疼痛药物（例如加巴喷丁）会对动物产生协同的抗伤害感受作用与GP120诱导的神经病（SA2）。我们将表征细胞激活并确定脊髓背角，大脑，脑脊液和血浆中的炎症细胞因子来自大鼠 GP120引起的神经病变并在接触后（SA3）。最后，我们将调查可能的一面可能与长时间接触绿光治疗有关的影响以准备引入这种对人类患者的疗法（SA4）。绿光治疗导致慢性疼痛减轻没有侧面由于其明显的有效性，安全性，低成本和可用性。我们的研究可能为当前的临床疗法提供了可能导致减少的临床疗法的辅助治疗艾滋病毒诱导神经性疼痛以及其他慢性疼痛状态的卵虫类药物。重要的是，随着疼痛的减轻，HIV患者可能更符合其抗逆转录病毒疗法。