Pain physician · 2026
SIRT1 Facilitates Beclin-1 Nuclear Translocation to Mitigate Nociceptive Hypersensitivity in Rats with Bone Cancer Pain by Restoring Autophagic Flux.
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He Qiuli, Li Wenjie, Deng Cuie, Zhang Zhiming, Deng Housheng
Аннотация
BACKGROUND: The etiology of bone cancer pain (BCP) is multifaceted, and effective therapeutic strategies for treating the condition remain elusive. Prior research has implicated sirtuin 1 (SIRT1) in the pathogenesis of BCP, suggesting the protein's potential to modulate autophagy and mitigate nociceptive sensitization; however, the underlying mechanisms of BCP are not fully understood.
OBJECTIVES: This study aimed to elucidate the role of SIRT1 in activating autophagy and its impact on the development of nociceptive hypersensitivity in a rat model of BCP.
STUDY DESIGN: Controlled animal study.
SETTING: Female Sprague Dawley® rats weighing 180-220 g were used.
METHODS: The BCP model was established by a single injection of Walker 256 breast cancer cells (10 µL, 107cells/mL) into the tibia. Mechanical pain sensitivity was assessed behaviorally using an Electronic von Frey Anesthesiometer.
RESULTS: Western blot (WB) analysis revealed reduced SIRT1 levels and elevated beclin-1 expression, an increased LC3II/LC3I ratio, and enhanced P62 expression in the dorsal horns of spinal cord tissues from rats with BCP. Immunofluorescence assays demonstrated co-localization of SIRT1 with neuronal cells and beclin-1. Subsequent experiments indicated that intrathecal administration of a SIRT1 agonist in rats with BCP postponed the downregulation of SIRT1, decreased the acetylation of beclin-1, and facilitated beclin-1 nuclear translocation. This treatment also led to a reduction in the LC3II/LC3I ratio and P62 expression levels. Collectively, these findings suggest that SIRT1 may ameliorate nociceptive hypersensitivity in rats with BCP through the promotion of beclin-1 nuclear translocation, thereby restoring autophagic flux..
LIMITATIONS: This study focused on peripheral/spinal mechanisms but not supraspinal/cortical contributions. Pharmacological tests were limited to a single time point, potentially missing dynamic pain changes during tumor progression. Nevertheless, the findings of this study offer valuable preliminary insights.
CONCLUSION: This research uncovers a novel mechanism of SIRT1 in the genesis of nociceptive hypersensitivity in BCP and offers potential avenues for therapeutic intervention.
OBJECTIVES: This study aimed to elucidate the role of SIRT1 in activating autophagy and its impact on the development of nociceptive hypersensitivity in a rat model of BCP.
STUDY DESIGN: Controlled animal study.
SETTING: Female Sprague Dawley® rats weighing 180-220 g were used.
METHODS: The BCP model was established by a single injection of Walker 256 breast cancer cells (10 µL, 107cells/mL) into the tibia. Mechanical pain sensitivity was assessed behaviorally using an Electronic von Frey Anesthesiometer.
RESULTS: Western blot (WB) analysis revealed reduced SIRT1 levels and elevated beclin-1 expression, an increased LC3II/LC3I ratio, and enhanced P62 expression in the dorsal horns of spinal cord tissues from rats with BCP. Immunofluorescence assays demonstrated co-localization of SIRT1 with neuronal cells and beclin-1. Subsequent experiments indicated that intrathecal administration of a SIRT1 agonist in rats with BCP postponed the downregulation of SIRT1, decreased the acetylation of beclin-1, and facilitated beclin-1 nuclear translocation. This treatment also led to a reduction in the LC3II/LC3I ratio and P62 expression levels. Collectively, these findings suggest that SIRT1 may ameliorate nociceptive hypersensitivity in rats with BCP through the promotion of beclin-1 nuclear translocation, thereby restoring autophagic flux..
LIMITATIONS: This study focused on peripheral/spinal mechanisms but not supraspinal/cortical contributions. Pharmacological tests were limited to a single time point, potentially missing dynamic pain changes during tumor progression. Nevertheless, the findings of this study offer valuable preliminary insights.
CONCLUSION: This research uncovers a novel mechanism of SIRT1 in the genesis of nociceptive hypersensitivity in BCP and offers potential avenues for therapeutic intervention.