Progress in Pathological and Therapeutic Research of HIV-Related Neuropathic Pain.

HIV-related neuropathic pain (HRNP) is a neurodegeneration that gradually develops during the long-term course of acquired immune deficiency syndrome (AIDS) and manifests as abnormal sock/sleeve-like symmetrical pain and nociceptive hyperalgesia in the extremities, which seriously reduces patient quality of life. To date, the pathogenesis of HRNP is not completely clear. There is a lack of effective clinical treatment for HRNP and it is becoming a challenge and hot spot for medical research. In this study, we conducted a systematic review of the progress of HRNP research in recent years including (1) the etiology, classification and clinical symptoms of HRNP, (2) the establishment of HRNP pathological models, (3) the pathological mechanisms underlying HRNP from three aspects: molecules, signaling pathways and cells, (4) the therapeutic strategies for HRNP, and (5) the limitations of recent HRNP research and the future research directions and prospects of HRNP. This detailed review provides new and systematic insight into the pathological mechanism of HRNP, which establishes a theoretical basis for the future exploitation of novel target drugs. HIV infection, antiretroviral therapy and opioid abuse contribute to the etiology of HRNP with symmetrical pain in both hands and feet, allodynia and hyperalgesia. The pathogenesis involves changes in cytokine expression, activation of signaling pathways and neuronal cell states. The therapy for HRNP should be patient-centered, integrating pharmacologic and nonpharmacologic treatments into multimodal intervention.

Antiretroviral Therapy for HIV Infection Induced-Neuropathic Pain, A Narrative Review.

BACKGROUND: Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS). AIDS is a human disease in which there is a systematic failure of the immune system, thereby leading to severe opportunistic infections. HIV is treated with antiretroviral therapy (ART), which helps in preventing the virus from replicating in the body. ART also enables the immune system to repair itself and restrict further injury. Nevertheless, the long-term use of ART leads to multiple neurological complications (e.g.neuropathic pain). Neuropathic pain (NP) arises if the nervous system is damaged or not working correctly. NP is is characterized by pain in both hands and feet and can hinder the quality of life (QOL) as it is always linked to impaired cognition, anxiety, depression, loss of function, among others. OBJECTIVE: To provide an overview of the clinical issues regarding the toxicity implications arising from the long-tern use of antiretroviral therapy (ART). METHOD: In this paper, we ascertained and summarized studies on manifestations of ART-induced neuropathic pain (ART-NP)-using the relevant and up-to-date facts from Google Scholar, and PubMed, among others. CONCLUSION: While ART assists in suppressing HIV and may help to lessen neurocognitive impairments, long-term use incurs toxicity to the central nervous system (CNS). Consequently, future studies must explore the effects of ART on adaptations in distinct regions of the CNS as well as the pathophysiological feature of ART-induced NP.

Identification of Key Genes and Pathways in Mouse Spinal Cord Involved in ddC-Induced Neuropathic Pain by Transcriptome Sequencing.

Highly active antiretroviral therapy (HAART) works effectively in inhibiting HIV replication in patients. However, the use of nucleoside reverse transcriptase inhibitors (NRTIs) often causes side effects of neuropathic pain, and its mechanism remains to be elucidated. Therefore, we aim to explore the mechanism of NRTIs-induced neuropathic pain at the transcriptome level. C57BL/6 J mice were given intraperitoneal injection of zalcitabine (ddC) or saline (control) for 2 weeks, during which the mechanical pain threshold of the mice was detected by von Frey test. Then the L3~L5 spinal segments of the mice were isolated and subsequently used for RNA sequencing (RNA-seq) on the last day of treatment. The mechanical pain threshold of mice given ddC decreased significantly. Compared with the control group, ddC caused significant changes in the expression of 135 genes, of which 66 upregulated and 69 downregulated. Enrichment analysis showed that the functions of these genes are mainly enriched in regulation of transcription, multicellular organism development, and cell differentiation, and the pathway is mainly enriched in the cGMP-PKG signaling pathway and AMPK signaling pathway. Furthermore, key genes such as Gabrd, Kcnd3, Npcd, Insr, Lypd6, Scd2, and Mef2d were also identified. These may serve as drug targets for the prevention or treatment of NRTI-induced neuropathic pain.