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.

项目概要/摘要 尽管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 使用联合抗逆转录病毒疗法（ART）。与其他人类免疫缺陷病毒 (HIV) 领域不同 研究（例如，与艾滋病毒相关的神经认知障碍、疫苗），慢性疼痛是一个尚未得到充分研究的领域 尽管 PLWH 中普遍存在疼痛、缺乏有效的镇痛治疗且不完整，但研究 对机制的理解。治疗策略的制定和对艾滋病毒的更好理解 由于缺乏合适的模拟动物模型，相关的神经性疼痛机制受到阻碍 PLWH 的慢性神经性疼痛。目前用于治疗 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，例如糖蛋白 120 (gp120)。该型号已服役 确定对该病毒蛋白的疼痛反应及其作用机制。不过，除了gp120之外， 其他 HIV 病毒蛋白、HIV-1 转录反式激活蛋白 (Tat) 和病毒蛋白 R (Vpr) 也会产生疼痛。 因此，单一 HIV 蛋白不太可能是 HIV 神经性疼痛的唯一贡献者，并且与 HIV 相似。 HIV 持续存在且病毒蛋白同时存在的慢性疾病。 拟议的研究将检验这一假设：感染 EcoHIV 的小鼠会出现类似神经性疼痛的症状。 行为和病理变化类似于患有慢性神经性疼痛的感染者。一个 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 检验这个假设。目标 1. 我们将进行全面的研究来描述 EcoHIV 中神经性疼痛的特征 被感染的老鼠。我们将使用一系列对感觉和自发/持续疼痛的行为评估。 分析临床上用于诊断 HIV 相关周围神经病变的标志物（例如， 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 还分析了神经炎症，它是诱发和维持慢性疼痛的关键因素。 拟议的研究将通过提供小动物来对艾滋病毒和疼痛领域产生重大影响 研究艾滋病毒相关神经性疼痛的模型一直缺乏。 EcoHIV 相关的特征 神经性疼痛模型将通过奠定基础来推进当前艾滋病毒背景下的疼痛研究 迫切需要的研究。