Role of macrophage autophagy in postoperative pain and inflammation in mice

Journal of Neuroinflammation

Research

Masakazu Kotoda¹  Kazuha Mitsui¹  Takashi Matsukawa¹  Masako Abe¹  Sohei Hishiyama¹  Yumi Kotoda²  Aakanksha Jain³ 

[1] Department of Anesthesiology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, 409-3898, Chuo, Yamanashi, Japan;Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, 409-3898, Chuo, Yamanashi, Japan;F.M. Kirby Neurobiology Center, Boston Children’s Hospital, and Department of Neurobiology, Harvard Medical School, 3 Blackfan Circle, 02115, Boston, MA, USA;

关键词: Autophagy;    Inflammation;    Macrophage;    Pain;    Surgery;   

DOI  :  10.1186/s12974-023-02795-w

 received in 2023-02-01, accepted in 2023-04-26,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundPostoperative pain and inflammation are significant complications following surgery. Strategies that aim to prevent excessive inflammation without hampering natural wound-healing are required for the management of postoperative pain and inflammation. However, the knowledge of the mechanisms and target pathways involved in these processes is lacking. Recent studies have revealed that autophagy in macrophages sequesters pro-inflammatory mediators, and it is therefore being recognized as a crucial process involved in regulating inflammation. In this study, we tested the hypothesis that autophagy in macrophages plays protective roles against postoperative pain and inflammation and investigated the underlying mechanisms.MethodsPostoperative pain was induced by plantar incision under isoflurane anesthesia in mice lacking macrophage autophagy (Atg5flox/flox LysMCre +) and their control littermates (Atg5flox/flox). Mechanical and thermal pain sensitivity, changes in weight distribution, spontaneous locomotor activity, tissue inflammation, and body weight were assessed at baseline and 1, 3, and 7 days after surgery. Monocyte/macrophage infiltration at the surgical site and inflammatory mediator expression levels were evaluated.ResultsAtg5flox/flox LysMCre + mice compared with the control mice exhibited lower mechanical and thermal pain thresholds and surgical/non-surgical hindlimb weight-bearing ratios. The augmented neurobehavioral symptoms observed in the Atg5flox/flox LysMCre + mice were associated with more severe paw inflammation, higher pro-inflammatory mediator mRNA expression, and more monocytes/macrophages at the surgical site.ConclusionThe lack of macrophage autophagy augmented postoperative pain and inflammation, which were accompanied by enhanced pro-inflammatory cytokine secretion and surgical-site monocyte/macrophage infiltration. Macrophage autophagy plays a protective role in postoperative pain and inflammation and can be a novel therapeutic target.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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