Products Cited in Publications Worldwide The effects of exercise on pain and anxiety following rotator cuff injury: the role of paraventricular nucleus synaptic plasticity

The effects of exercise on pain and anxiety following rotator cuff injury: the role of paraventricular nucleus synaptic plasticity

Liu, Shen; Huang, Tingmo; Wan, Liyang; Xiong, Yinghong; Zeng, Liyue; Du, Ruixue; Lin, Ziyang; Guo, Zilong; Lu, Hongbin; Xu, Daqi

DOI:

Abstract

Background: Rotator cuff injury (RCI) often leads to chronic pain and anxiety, yet the underlying neural mechanisms remain unclear. This study explored central mechanisms linking RCI to these symptoms and assessed treadmill exercise (TE) as a therapeutic intervention in mice. Methods: Male C57BL/6 mice underwent RCI surgery and were randomized into Sham, RCI, or TE groups (TE initiated on postoperative day 7). Mechanical hypersensitivity and anxiety-like behaviors were evaluated via von Frey, elevated plus maze, and open field tests. Synaptic plasticity proteins and structures in the paraventricular nucleus (PVN) were analyzed using immunofluorescence, Western blotting, electron microscopy, and Golgi staining. The brain-derived neurotrophic factor-tropomyosin receptor kinase B (BDNF-TrkB) pathway’s role was tested using the TrkB inhibitor ANA-12. Results: RCI elicited notable alterations in synaptic structure within the PVN, characterized by decreased synaptophysin expression, increased growth-associated protein 43 expression, and synaptic microstructural abnormalities. These synaptic modifications were correlated with the manifestation of hyperalgesia and anxiety-like behaviors in murine models. TE reversed these synaptic changes and improved pain and anxiety symptoms. Mechanistically, TE activated the BDNF-TrkB signaling pathway in the PVN, which was essential for its therapeutic effects. Pharmacological blockade of the TrkB receptor using ANA-12 attenuated the therapeutic benefits of TE, confirming the critical role of BDNF-TrkB signaling pathway. Conclusion: TE mitigates RCI-related pain and anxiety by restoring PVN synaptic plasticity via BDNF-TrkB signaling, underscoring exercise’s therapeutic potential. The translational potential of this article: The study reveals new insights into the central neural mechanisms of pain and anxiety after RCI, highlighting synaptic plasticity changes in the PVN. It clarifies the link between peripheral injury and central nervous system alterations, guiding clinicians toward more targeted and effective treatments.

Keywords

Rotator cuff injury ; Pain ; Anxiety ; Structural plasticity ; Treadmill exercise

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ANA-12

A327589219766-25-398%

ANA-12

15.0/1mg

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