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.

项目总结/摘要 慢性疼痛是人类免疫缺陷病毒-1（PLWH）感染者的主要健康状况， 联合抗逆转录病毒治疗（ART）。与其他人类免疫缺陷病毒（HIV）领域不同， 研究（例如，艾滋病相关的神经认知障碍，疫苗），慢性疼痛是一个研究不足的领域， 尽管PLWH疼痛的患病率，缺乏有效的镇痛治疗， 了解机制。制定治疗战略和更好地了解艾滋病毒- 相关的神经性疼痛机制由于缺乏合适的动物模型而受到阻碍 PLWH中的慢性神经性疼痛。目前用于HIV相关神经性疼痛的小动物模型包括 急性施用单一HIV病毒蛋白，如糖蛋白120（gp 120）。这种模式已经服务于 以确定这种病毒蛋白的疼痛反应及其作用机制。然而，除了GP 120之外， 其它HIV病毒蛋白、HIV-1转录反式激活因子（达特）和病毒蛋白R（Vpr）可产生疼痛。 因此，单个HIV蛋白不太可能是HIV神经性疼痛的唯一贡献者，并且模仿HIV蛋白。 持续存在HIV和同时存在病毒蛋白的慢性疾病。 拟议的研究将测试EcoHIV感染小鼠发展神经性疼痛样的假设， 具有行为和病理变化的病症，类似于具有慢性神经性疼痛的PLWH。一 行为学、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 测试这个假设。目标1。我们将进行全面的研究，以表征EcoHIV中的神经性疼痛- 感染的老鼠我们将使用一系列感觉和自发/持续疼痛的行为评估。 分析临床上用于诊断HIV相关周围神经病变的标志物（例如，减少 表皮内神经纤维密度）将用于验证EcoHIV相关的神经性疼痛模型。我们将 还分析神经炎症，在诱导和维持慢性疼痛的关键球员。 拟议的研究将对艾滋病毒和疼痛领域产生重大影响， 模型来研究HIV相关的神经病理性疼痛，这是一直缺乏的。EcoHIV相关的表征 神经病理性疼痛模型将通过为以下方面奠定基础来推进目前对艾滋病毒背景下疼痛的研究： 迫切需要的研究。