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1.
Curr HIV Res ; 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056867

RESUMO

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.

2.
J Neuroimmune Pharmacol ; 17(3-4): 553-575, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35059976

RESUMO

Human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS), remains one of the most diverse crucial health and development challenges around the world. People infected with HIV constitute a large patient population, and a significant number of them experience neuropathic pain. To study the key mechanisms that mediate HIV-induced neuropathic pain (HNP), we established an HNP mouse model via intrathecal injection of the HIV-1 envelope glycoprotein gp120. The L3~L5 spinal cord was isolated on postoperative days 1/12 (POD1/12), 1 (POD1), and 14 (POD14) for RNA sequencing to investigate the gene expression profiles of the initiation, transition, and maintenance stages of HNP. A total of 1682, 430, and 413 differentially expressed genes were obtained in POD1/12, POD1, and POD14, respectively, and their similarity was low. Bioinformatics analysis confirmed that POD1/12, POD1, and POD14 exhibited different biological processes and signaling pathways. Inflammation, oxidative damage, apoptosis, and inflammation-related signaling pathways were enriched on POD1/12. Inflammation, chemokine activity, and downstream signaling regulated by proinflammatory cytokines, such as the MTOR signaling pathway, were enriched on POD1, while downregulation of ion channel activity, mitochondrial damage, endocytosis, MAPK and neurotrophic signaling pathways developed on POD14. Additionally, we screened key genes and candidate genes, which were verified at the transcriptional and translational levels. Our results suggest that the initiation and maintenance of HNP are regulated by different molecular mechanisms. Therefore, our research may yield a fresh and deeper understanding of the mechanisms underlying HNP, providing accurate molecular targets for HNP therapy.


Assuntos
Proteína gp120 do Envelope de HIV , Infecções por HIV , Neuralgia , Animais , Humanos , Camundongos , Proteína gp120 do Envelope de HIV/toxicidade , Infecções por HIV/metabolismo , HIV-1 , Neuralgia/etiologia , Neuralgia/fisiopatologia , Análise de Sequência de RNA , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia
3.
J Mol Neurosci ; 71(3): 651-661, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32812184

RESUMO

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.


Assuntos
Neuralgia/genética , Medula Espinal/metabolismo , Transcriptoma , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuralgia/etiologia , Neuralgia/metabolismo , Inibidores da Transcriptase Reversa/toxicidade , Transdução de Sinais , Zalcitabina/toxicidade
4.
Cell Mol Neurobiol ; 40(7): 1075-1085, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32100186

RESUMO

Human immunodeficiency virus (HIV)-related neuropathic pain includes HIV-induced neuropathic pain (HNP) and antiretroviral therapy-induced neuropathic pain (ART-NP). A significant amount of evidence from the past few years has shown that the development of HIV-related neuropathic pain is closely related to the activation of the Wnt signaling pathway in the spinal cord. This review summarizes the function of the spinal Wnt signaling pathway in HIV-induced neuropathic pain, focusing on the role of the spinal Wnt signaling pathway in HNP, and provides a theoretical basis for further studies and the exploration of new target drugs.


Assuntos
Infecções por HIV/metabolismo , Neuralgia/metabolismo , Neuralgia/virologia , Medula Espinal/metabolismo , Via de Sinalização Wnt/fisiologia , Animais , Modelos Animais de Doenças , Desenvolvimento de Medicamentos/métodos , Infecções por HIV/virologia , Humanos , Medula Espinal/virologia
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