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Rapid Isolation of Dorsal Root Ganglion Macrophages
Published on: September 7, 2019
Role of macrophage autophagy in postoperative pain and inflammation in mice
Kazuha Mitsui1, Sohei Hishiyama1, Aakanksha Jain2
1Department of Anesthesiology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Background:
Postoperative 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.
Methods:
Postoperative 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.
Results:
Atg5flox/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.
Conclusion:
The 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.
Insights
Macrophage autophagy protects against postoperative pain and inflammation by reducing inflammatory mediators. Impaired autophagy in macrophages exacerbates pain and inflammation following surgery.
Area of Science:
- Immunology
- Molecular Biology
- Pain Research
Background:
- Postoperative pain and inflammation are common surgical complications.
- Effective management requires strategies that reduce inflammation without hindering wound healing.
- Macrophage autophagy is increasingly recognized for its role in regulating inflammation.
Purpose of the Study:
- To investigate the protective role of macrophage autophagy in postoperative pain and inflammation.
- To elucidate the underlying mechanisms of autophagy in regulating these processes.
Main Methods:
- Mice lacking macrophage autophagy (Atg5flox/flox LysMCre+) and controls (Atg5flox/flox) underwent plantar incision surgery.
- Assessed pain sensitivity, weight distribution, activity, inflammation, and body weight.
- Evaluated monocyte/macrophage infiltration and inflammatory mediator expression.
Main Results:
- Mice lacking macrophage autophagy showed increased pain sensitivity and impaired weight-bearing.
- These mice exhibited more severe paw inflammation and higher pro-inflammatory mediator expression.
- Increased monocyte/macrophage infiltration was observed at the surgical site in mice with deficient autophagy.
Conclusions:
- Macrophage autophagy deficiency exacerbates postoperative pain and inflammation.
- This exacerbation is linked to increased pro-inflammatory cytokine secretion and immune cell infiltration.
- Macrophage autophagy plays a protective role and represents a potential therapeutic target for postoperative pain and inflammation.
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