Green Light Therapy for Chronic Pain

绿光疗法治疗慢性疼痛

基本信息

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
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/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

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.

该应用解决了人类对有效非药物治疗的迫切需求 1 型免疫缺陷病毒 (HIV) 感觉神经病 (HIV-SN) 可能与这种神经病有关。单独的病毒感染，可能涉及包膜糖蛋白 gp120 的作用或药物引起的毒性；与使用核苷类似物逆转录酶抑制剂（NRTI）作为治疗药物相关的神经病该项目的首席研究员 Mohab Ibrahim 博士是高效抗逆转录病毒疗法的组成部分。与该项目的联合研究员 Rajesh Khanna 博士一起，首先证明了低强度绿光为幼稚动物提供持久的镇痛作用，未发现任何副作用，并且运动性能也得到改善。预期作用未受损，可能是由于观察到内源性阿片类药物表达增加。他们最近的研究也证明了脊髓和可能的炎症因子的减少。脊髓神经结扎大鼠的机械和热超敏反应——慢性过敏模型因此，了解绿光介导的抗疼痛机制。将是将其开发为一种新型疗法的关键的第一步，我们将检验我们的假设。暴露在绿光下会减少由于接触而引起的热、机械过敏。我们将用四种方法来验证这一假设。使用 HIV 引起的疼痛的包膜糖蛋白 gp120 模型实现相关但独立的具体目标我们首先确定周围神经病变所需的时间进程和光强度（勒克斯水平）。 HIV引起的周围疼痛的gp120模型中热和机械超敏反应的逆转神经病变和与抗逆转录病毒治疗相关的机械过敏（SA1）。确定内源性阿片类药物系统在调节绿光发射效应中的贡献二极管 (GLED) 以及是否固定光强度/持续时间以及 mu 阿片受体激动剂或非阿片类神经性止痛药（例如加巴喷丁）可在动物中产生协同抗伤害作用我们将表征 gp120 诱导的神经病 (SA2) 的细胞激活并确定其水平。大鼠脊髓背角、大脑、脑脊液和血浆中的炎症细胞因子 gp120 诱发的神经病变和 GLED 暴露后 (SA3) 最后，我们将研究可能的一面。可能与长期接触绿光疗法以准备引入相关的影响这种疗法对人类患者（SA4）可减少慢性疼痛，无副作用。由于其明显的功效、安全性和低成本，其效果有望轻松转化为临床我们的研究可能为当前的临床疗法提供辅助，可能会导致减少。阿片类药物可治疗艾滋病毒引起的神经性疼痛以及其他慢性疼痛状态。随着疼痛的减轻，艾滋病毒患者可能会更愿意接受抗逆转录病毒治疗。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Green Light Exposure Elicits Anti-inflammation, Endogenous Opioid Release and Dampens Synaptic Potentiation to Relieve Post-surgical Pain.

绿光照射可引发抗炎、内源性阿片类药物释放并抑制突触增强，从而缓解术后疼痛。

DOI：
发表时间：
2023-03
期刊：
影响因子：
0
作者：
Martin, Laurent F;Cheng, Kevin;Washington, Stephanie M;Denton, Millie;Goel, Vasudha;Khandekar, Maithili;Largent;Patwardhan, Amol;Ibrahim, Mohab M
通讯作者：
Ibrahim, Mohab M

Green Light Exposure Improves Pain and Quality of Life in Fibromyalgia Patients: A Preliminary One-Way Crossover Clinical Trial.

绿光照射可改善纤维肌痛患者的疼痛和生活质量：一项初步单向交叉临床试验。

DOI：
10.1093/pm/pnaa329
发表时间：
2020-11-06
期刊：
Pain medicine
影响因子：
3.1
作者：
Laurent F Martin;F. Porreca;Elizabeth I. Mata;Michelle Salloum;Vasudha Goel;Pooja Gunnala;W. D. S. Killgore;Sejal V. Jain;Felesia N Jones;R. Khanna;A. Patwardhan;M. Ibrahim
通讯作者：
M. Ibrahim

Mechanisms and Pathways of Pain Photobiomodulation: A Narrative Review.

疼痛光生物调节的机制和途径：叙事回顾。

DOI：
10.1016/j.jpain.2021.02.005
发表时间：
2021-07
期刊：
The journal of pain
影响因子：
0
作者：
Cheng K;Martin LF;Slepian MJ;Patwardhan AM;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.

绿光照射对偏头痛患者头痛频率和生活质量的评估：一项初步的单向交叉临床试验。

DOI：
发表时间：
2021
期刊：
影响因子：
0
作者：
Martin, Laurent F;Patwardhan, Amol M;Jain, Sejal V;Salloum, Michelle M;Freeman, Julia;Khanna, Rajesh;Gannala, Pooja;Goel, Vasudha;Jones;Killgore, William Ds;Porreca, Frank;Ibrahim, Mohab M
通讯作者：
Ibrahim, Mohab M

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

绿光镇痛作用以及热和机械超敏反应的逆转依赖于内源性阿片类药物系统刺激。

DOI：
发表时间：
2021-12
期刊：
影响因子：
0
作者：
Martin, Laurent F;Moutal, Aubin;Cheng, Kevin;Washington, Stephanie M;Calligaro, Hugo;Goel, Vasudha;Kranz, Tracy;Largent;Khanna, Rajesh;Patwardhan, Amol;Ibrahim, Mohab M
通讯作者：
Ibrahim, Mohab M