ArticleJournal of pain research2022
Translocator Protein (TSPO) Alleviates Neuropathic Pain by Activating Spinal Autophagy and Nuclear SIRT1/PGC-1α Signaling in a Rat L5 SNL Model.
Article in Journal of pain research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Effect of intramuscular diazepam infusion on herpes zoster-related pain in older patients: a randomized, double-blind, placebo-controlled trial.BMC anesthesiology · 2024Trial
- Ro5-4864, a ligand of the mitochondrial translocator protein, protects against heart failure in mice via regulation of the p62-Keap1-Nrf2 axis.The Journal of physiology · 2026Article
- In vitro γ-aminobutyric acid A (GABACommunications chemistry · 2026Article
- Machine learning based screening of biomarkers associated with cell death and immunosuppression of multiple life stages sepsis populations.Scientific reports · 2025Article
- Spinal astrocytes involved in the pathogenesis and treatment of neuropathic pain.Frontiers in cellular neuroscience · 2025Review
- Activation of G-protein-coupled receptor 39 reduces neuropathic pain in a rat model.Neural regeneration research · 2024Article
- High-voltage pulsed radiofrequency improves ultrastructure of DRG and enhances spinal microglial autophagy to ameliorate neuropathic pain induced by SNI.Scientific reports · 2024Article
- Neuroimmune activation and increased brain aging in chronic pain patients after the COVID-19 pandemic onset.Brain, behavior, and immunity · 2024Article
- Targeting the Main Sources of Reactive Oxygen Species Production: Possible Therapeutic Implications in Chronic Pain.Current neuropharmacology · 2024Review
- Up-and-coming Radiotracers for Imaging Pain Generators.Seminars in musculoskeletal radiology · 2023Article
- Review
- PGC1α: an emerging therapeutic target for chemotherapy-induced peripheral neuropathy.Therapeutic advances in neurological disorders · 2023Review
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Authors and funding
5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Purpose: Recent studies showed promotion of astrocyte autophagy in the spinal cord would provide analgesic effects. Silent information regulator T1 (SIRT1) and α subunit of peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1α) are two master regulators of endogenous antioxidant defense and mitochondrial biogenesis. They play vital roles in both autophagy and neuropathic pain (NP). Our previous study showed that TSPO agonist Ro5-4864 elicited potent analgesic effects against NP, but the mechanisms remain unclear. This study aims to investigate the effects of TSPO agonist Ro5-4864 on autophagy and nuclear SIRT1/PGC-1α signaling in spinal dorsal horn. Methods: A rat model of L5 spinal nerve ligation (SNL) was adopted. Rats were randomly assigned to the Sham group, the SNL group, the Ro (TSPO agonist Ro5-4864) group and the Ro+3-MA group. The behavior assessments were conducted at baseline, on Day 1, 3, 7 and 14 after SNL. The autophagy-related proteins (ATG7, Beclin1, LC3, and P62) in spinal dorsal horn were assayed and the nuclear SIRT1/PGC-1α and downstream factors were analyzed. Results: Ro5-4864 alleviated the mechanical allodynia induced by SNL (P < 0.01 vs the SNL group), which could be totally abrogated by autophagy inhibitor 3-MA (P < 0.01 vs the Ro group). SNL induced elevated ATG7 (P < 0.01), Beclin1 (P < 0.01) and LC3-II/LC3-I (P < 0.01) contents and P62 accumulation (P < 0.01) on Day 7 and Day 14, which suggested an autophagy flux impairment. Ro5-4864 augmented ATG7 (P < 0.01), Beclin1 (P < 0.01) and LC3-II/LC3-I (P < 0.05) with decreased P62 (P < 0.01), which indicated a more fluent autophagic process. These effects were also totally abrogated by 3-MA (P < 0.01). Furthermore, Ro5-4864 activated the spinal nuclear SIRT1/PGC-1α signaling pathway. Conclusion: TSPO improved both autophagy impairment and mitochondrial biogenesis, which may provide a new strategy for the treatment of NP.
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