Green Light Therapy for Chronic Pain

绿光疗法治疗慢性疼痛

• 批准号: 10400839
• 负责人: Mohab M Ibrahim
• 金额: $ 34.54万
• 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/10400839
• 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; Persons; 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; pain scale; 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.

本申请解决了对人类肿瘤的有效非药物治疗的迫切需求。 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 单独的病毒感染，可能涉及包膜糖蛋白gp 120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）作为 高效抗逆转录病毒疗法的组成部分。Mohab Ibrahim博士，这个项目的首席研究员， 沿着的还有Rajesh卡纳博士，他是这个项目的共同研究者，他首先发现低强度的绿色光 在幼稚动物中提供持久的抗伤害感受。没有发现任何副作用，运动性能 没有受损。这种抗伤害感受作用可能是由于内源性阿片样物质表达增加所致。 脊髓，并可能减少炎症因子。他们最近的工作也证明了 脊髓神经结扎大鼠的机械和热超敏反应-慢性 神经性疼痛因此，了解绿色光介导的抗伤害感受的机制 这将是将其发展为一种新型疗法的关键的第一步。我们将测试我们的假设， 暴露于绿色光将减少由于接合的热、机械超敏性， 内源性阿片系统和减少炎症介质。我们将用四个例子来验证这个假设。 使用HIV诱导疼痛的包膜糖蛋白gp 120模型的相关但独立的特定目的 周围神经病变我们将首先确定时间进程和光强度（勒克斯水平）所需的 逆转HIV诱导的外周疼痛的gp 120模型中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超敏反应（SA 1）。接下来我们就 确定内源性阿片样物质系统在介导绿色光发射效应中的作用 以及固定的光强度/持续时间沿着μ阿片受体激动剂或非阿片受体激动剂是否与μ阿片受体激动剂一起使用。 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感受作用 gp 120诱导的神经病变（SA 2）。我们将描述细胞活化的特征，并确定 大鼠脊髓背角、脑、脑脊液和血浆中的炎性细胞因子 gp 120诱导的神经病变和GLED暴露后（SA 3）。最后，我们将调查可能的一面， 可能与长时间暴露于绿色光治疗相关的影响， 该疗法用于人类患者（SA 4）。绿色光疗法可减少慢性疼痛， 由于其明显的疗效、安全性、低成本， 和可用性。我们的研究可能为目前的临床治疗提供一种辅助手段， 阿片类药物治疗HIV诱导的神经性疼痛以及其他慢性疼痛状态。重要的是， 随着疼痛的减轻，艾滋病患者可能更愿意接受抗逆转录病毒治疗。

项目成果

Mechanisms and Pathways of Pain Photobiomodulation: A Narrative Review.

• DOI: 10.1016/j.jpain.2021.02.005
• 发表时间: 2021-07
• 期刊: The journal of pain
• 作者: Cheng K;Martin LF;Slepian MJ;Patwardhan AM;Ibrahim MM
• 通讯作者: Ibrahim MM

Green Light Antinociceptive and Reversal of Thermal and Mechanical Hypersensitivity Effects Rely on Endogenous Opioid System Stimulation.

• DOI: 10.1016/j.jpain.2021.05.006
• 发表时间: 2021-12
• 期刊: The journal of pain
• 作者: Martin LF;Moutal A;Cheng K;Washington SM;Calligaro H;Goel V;Kranz T;Largent-Milnes TM;Khanna R;Patwardhan A;Ibrahim MM
• 通讯作者: Ibrahim MM

Evaluation of green light exposure on headache frequency and quality of life in migraine patients: A preliminary one-way cross-over clinical trial.

• DOI: 10.1177/0333102420956711
• 发表时间: 2021-03
• 期刊: Cephalalgia : an international journal of headache
• 作者: Martin LF;Patwardhan AM;Jain SV;Salloum MM;Freeman J;Khanna R;Gannala P;Goel V;Jones-MacFarland FN;Killgore WD;Porreca F;Ibrahim MM
• 通讯作者: Ibrahim MM