Green Light Therapy for Chronic Pain

绿光疗法治疗慢性疼痛

• 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
• 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

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.

这项应用解决了对人类有效的非药物治疗的迫切需要 免疫缺陷病毒1型(HIV)感觉神经病(HIV-SN)。这种神经病变可能与 单纯的病毒感染，可能涉及包膜糖蛋白gp120的作用；或药物诱导的毒性 与使用核苷类似物逆转录酶抑制剂(NRTI)相关的神经病变 高效抗逆转录病毒疗法的组成部分。莫哈布·易卜拉欣博士，这个项目的首席研究员， 与该项目的联合研究员拉杰什·坎纳博士一起，首次展示了低强度的绿灯 为幼稚的动物提供了持久的抗伤害性感觉。没有注意到副作用，运动性能 没有受损。这种抗伤害性感觉可能是由于观察到内源性阿片类药物在 脊髓，可能是炎症因子的减少。他们最近的工作也证明了 脊髓神经结扎大鼠的机械和温度超敏反应--慢性 神经性疼痛。因此，了解绿光介导的抗伤害感受的机制 将是将其发展为一种新的治疗形式的关键的第一步。我们将检验我们的假设 暴露在绿光下将减少热，机械过敏，由于接触 内源性阿片系统，减少炎症介质。我们将用四个例子来检验这一假设 使用HIV诱导疼痛的包膜糖蛋白gp120模型的相关但独立的特定靶点 周围神经病。我们将首先确定所需的时间进程和光线强度(勒克斯级) 逆转HIV诱导的外周疼痛gp120模型的热和机械超敏反应 神经病变和与抗逆转录病毒治疗相关的机械过敏(SA1)。接下来，我们将 确定内源性阿片系统在调节绿光发射效应中的作用 二极管(GLLED)以及是否有固定的光强度/持续时间与MU阿片受体激动剂或非 阿片类神经性疼痛药物，如加巴喷丁，在动物中产生协同抗伤害效应 Gp120诱导的神经病(SA2)。我们将确定细胞激活的特征，并确定其水平 大鼠脊髓背角、脑、脑脊液和血浆中炎性细胞因子的变化 Gp120诱导的神经病和暴露后的神经病(SA3)。最后，我们将调查可能的方面 可能与长期暴露在绿光疗法中准备引入 这种疗法适用于人类患者(SA4)。绿光疗法可减少无副作用的慢性疼痛 由于其明显的有效性、安全性、低成本，疗效有望很容易地移植到临床上。 和可用性。我们的研究可能会为目前的临床治疗提供一个补充，可能会导致减少 阿片类药物用于管理艾滋病毒引起的神经病理性疼痛以及其他慢性疼痛状态。重要的是 随着疼痛的减轻，艾滋病毒患者可能更愿意接受抗逆转录病毒治疗。