EcoHIV and neuropathic pain

EcoHIV 和神经性疼痛

• 批准号: 10760678
• 负责人: Khalid Benamar
• 金额: $ 22.2万
• 依托单位: UNIVERSITY OF TEXAS RIO GRANDE VALLEY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10760678
• 关键词: Acute; Address; Adherence; Affect; Age; Analgesics; Animal Model; Animals; Area; Behavior; Behavior assessment; Behavioral; Biochemistry; Biological; Biopsy; CD4 Positive T Lymphocytes; Cells; Characteristics; Chronic; Clinical; Clinical Data; Cognitive deficits; DNA; Development; Dysesthesias; Ensure; Esthesia; Female; Genetic Transcription; Glycoproteins; HIV; HIV Infections; HIV diagnosis; HIV-1; HIV-associated neurocognitive disorder; Health; Histopathology; Hypersensitivity; Individual; Infection; Injections; Intraperitoneal Injections; Knowledge; Light; Longitudinal Studies; Maintenance; Mental Depression; Modeling; Molecular Biology; Mus; Needles; Nerve Fibers; Neuropathy; Outcome; Pain; Pathologic; Patients; Peripheral Nervous System Diseases; Persistent pain; Persons; Pharmacology; Physical Function; Prevalence; Proteins; Quality of life; Reporting; Research; Role; Sensory; Severities; Sex Differences; Skin; Spinal Cord; Stimulus; Testing; Therapeutic; Therapeutic Studies; Touch sensation; Trans-Activators; Transcription Coactivator; Vaccines; Viral; Viral Proteins; age difference; allodynia; antiretroviral therapy; approach behavior; behavior test; chronic neuropathic pain; chronic pain; comorbidity; cost; density; health care availability; human old age (65+); interdisciplinary approach; male; mechanical allodynia; midbrain central gray substance; neuroinflammation; pain model; pain sensation; painful neuropathy; pharmacologic; public health relevance; receptor; response; sex; side effect; substance use; therapeutic development; therapeutically effective; tool

PROJECT SUMMARY/ABSTRACT Chronic pain is a major health condition in people living with Human Immunodeficiency Virus-1 (PLWH) despite the use of combined antiretroviral therapy (ART). Unlike other human immunodeficiency virus (HIV) areas of research (e.g., HIV-associated neurocognitive disorder, vaccine), chronic pain is an understudied area of research despite the prevalence of pain in PLWH, lack of effective analgesic therapy, and incomplete understanding of mechanisms. The development of therapeutic strategies and a better understanding of HIV- related neuropathic pain mechanisms have been hampered by the lack of a suitable animal model that mimics chronic neuropathic pain in PLWH. The current small animal model for HIV-related neuropathic pain consists of the acute administration of a single HIV viral protein, such as glycoprotein 120 (gp120). This model has served to determine the pain response to this viral protein and its mechanism of action. However, in addition to gp120, other HIV viral proteins, HIV-1 transactivator of transcription (Tat), and Viral protein R (Vpr) can produce pain. Therefore, a single HIV protein is unlikely to be the only contributor to HIV-neuropathic pain and mimics the HIV chronic condition where there is a continuous presence of HIV and a simultaneous presence of viral proteins. The proposed studies will test the hypothesis that EcoHIV-infected mice develop a neuropathic pain-like condition with behavioral and pathological changes that mimic PLWH with chronic neuropathic pain. A multidisciplinary approach of behavior, pharmacology, molecular biology, biochemistry, and histopathology will test this hypothesis. Aim 1. We will perform comprehensive studies to characterize neuropathic pain in EcoHIV- infected mice. We will use a battery of behavioral assessments of sensory and spontaneous/ongoing pain. Analyzing markers clinically used for the diagnosis of HIV-associated peripheral neuropathy (e.g., decrease in intraepidermal nerve fiber density) will serve to validate the EcoHIV-associated neuropathic pain model. We will also analyze neuroinflammation, a key player in the induction and maintenance of chronic pain. The proposed studies will have a significant impact on the fields of HIV and pain by providing a small animal model to study HIV-related neuropathic pain, which has been lacking. Characterization of the EcoHIV-related neuropathic pain model will advance current research on pain in the context of HIV by laying the groundwork for urgently and critically needed studies.

项目摘要/摘要 慢性疼痛是人类免疫缺陷病毒-1（PLWH）患者的主要健康状况 联合抗逆转录病毒疗法（ART）的使用。与其他人类免疫缺陷病毒（HIV）不同 研究（例如，与HIV相关的神经认知疾病，疫苗），慢性疼痛是研究的领域 尽管PLWH的疼痛患病率流行，缺乏有效的镇痛疗法，并且不完整 理解机制。治疗策略的发展以及对艾滋病毒的更好理解 缺乏合适的动物模型来阻碍相关的神经性疼痛机制 PLWH中的慢性神经性疼痛。当前用于HIV相关神经性疼痛的小动物模型包括 单一HIV病毒蛋白的急性给药，例如糖蛋白120（GP120）。这个模型已经服务 确定对这种病毒蛋白的疼痛反应及其作用机理。但是，除了GP120之外， 其他HIV病毒蛋白，转录（TAT）的HIV-1反式激活剂和病毒蛋白R（VPR）会产生疼痛。 因此，单一的HIV蛋白不可能成为HIV - 神经性疼痛和模仿HIV的唯一促成者 慢性病，其中持续存在HIV和同时存在病毒蛋白。 拟议的研究将检验以下假设，即生态感染的小鼠会形成神经性疼痛样 与慢性神经性疼痛模仿PLWH的行为和病理变化的条件。一个 行为，药理学，分子生物学，生物化学和组织病理学的多学科方法将 检验此假设。 AIM 1。我们将进行全面的研究，以表征Ecohiv-的神经性疼痛 感染的小鼠。我们将使用一系列对感觉和自发/持续疼痛的行为评估。 分析用于诊断HIV相关周围神经病的临床标记（例如，减少 皮肤内神经纤维密度）将有助于验证与生态相关的神经性疼痛模型。我们将 还分析神经炎症，这是慢性疼痛诱导和维持的关键参与者。 拟议的研究将通过提供小动物来对艾滋病毒和疼痛的田野产生重大影响 研究与HIV相关的神经性疼痛的模型，该模型一直缺乏。与Ecohiv相关的表征 神经性疼痛模型将通过为艾滋病背景下的疼痛进行当前的研究。 急需的研究。