ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2018
Nucleoside Reverse Transcriptase Inhibitors (NRTIs) Induce Pathological Pain through Wnt5a-Mediated Neuroinflammation in Aging Mice.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Progress in Pathological and Therapeutic Research of HIV-Related Neuropathic Pain.Cellular and molecular neurobiology · 2023Pooled it
- Wnt5a-Induced Exosomes From Bone Marrow Mesenchymal Stem Cells Promote Spinal Cord Injury Repair by Modulating Immune Cell Phenotypes and Alleviating Neuroinflammation via the NF-κB Pathway.CNS neuroscience & therapeutics · 2026Article
- HIV-associated sensory neuropathy: current progress and future challenges.NeuroImmune pharmacology and therapeutics · 2025Review
- Tet1-mediated 5hmC regulates hippocampal neuroinflammation via wnt signaling as a novel mechanism in obstructive sleep apnoea leads to cognitive deficit.Journal of neuroinflammation · 2024Article
- Nucleoside Reverse Transcriptase Inhibitors Are the Major Class of HIV Antiretroviral Therapeutics That Induce Neuropathic Pain in Mice.International journal of molecular sciences · 2024Article
- Exploring viral neuropathic pain: Molecular mechanisms and therapeutic implications.PLoS pathogens · 2024Review
- Pathogenic mechanisms of human immunodeficiency virus (HIV)-associated pain.Molecular psychiatry · 2023Review
- Sex Differences in the Expression of Neuroimmune Molecules in the Spinal Cord of a Mouse Model of Antiretroviral-Induced Neuropathic Pain.Biomedicines · 2023Article
- DNA damage and repair in age-related inflammation.Nature reviews. Immunology · 2023Review
- Development of opioid-induced hyperalgesia depends on reactive astrocytes controlled by Wnt5a signaling.Molecular psychiatry · 2023Article
- Persistent sensory changes and sex differences in transgenic mice conditionally expressing HIV-1 Tat regulatory protein.Experimental neurology · 2022Article
- A neuron-to-astrocyte Wnt5a signal governs astrogliosis during HIV-associated pain pathogenesis.Brain : a journal of neurology · 2022Article
- Axon Guidance Molecules and Pain.Cells · 2022Review
- Reactive astrocytes in pain neural circuit pathogenesis.Current opinion in neurobiology · 2022Review
- Chronic pain and infection: mechanisms, causes, conditions, treatments, and controversies.BMJ medicine · 2022Review
- Effects of Wnt5a overexpression in spinal cord injury.Journal of cellular and molecular medicine · 2021Article
- Identification of Key Genes and Pathways in Mouse Spinal Cord Involved in ddC-Induced Neuropathic Pain by Transcriptome Sequencing.Journal of molecular neuroscience : MN · 2021Article
- Article
- The Interplay Between Neuroinfections, the Immune System and Neurological Disorders: A Focus on Africa.Frontiers in immunology · 2021Review
- Neuroinflammation in HIV-Related Neuropathic Pain.Frontiers in pharmacology · 2021Review
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Highly Active Antiretroviral Therapy (HAART) has significantly contributed to the increase of HIV-infected survivors over 50 years of age. Unfortunately, patients are required to stay on long-term HAART, which may be causally related to the development of neurological problems such as chronic pain. Little is known about the contribution of HAART or its therapeutic agents to the pathogenesis of pain during aging. In this study, we determined the effect of nucleoside reverse transcriptase inhibitors (NRTIs) on the development of mechanical allodynia and the potential underlying mechanism in aging mice (15.5 months). We found that systemic administration of individual NRTIs, including ddC (2'-3'-dideoxycytidine), ddI (didanosine), AZT (3'-azido-3'-deoxythymidine) and d4T (2', 3'-didehydro-2', 3'-dideoxythymidine), induced allodynia in similar magnitudes and temporal profiles. We used ddC as a representative to investigate cellular and molecular processes induced by NRTIs in the spinal cord that probably underlie the development of allodynia. The results showed that ddC caused evident neuroinflammation in the spinal cord, suggested by the up-regulation of proinflammatory cytokines TNF-α and IL-1β and the reactions of microglia and astrocytes. In addition, we found that Wnt5a, a critical regulator of neuroinflammation, was also up-regulated. Pharmacological inhibition of Wnt5a blocked ddC-induced up-regulation of TNF-α and astrocyte reaction, while activation of Wnt5a signaling potentiated these processes. Furthermore, our data showed that inhibition of Wnt5a significantly reversed ddC-induced mechanical allodynia in aging mice. The results collectively suggest that NRTIs may contribute to the development of chronic pain in aging patients by inducing Wnt5a-regulated neuroinflammation.
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Registered trials
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