RRC ID 75825
Author Mitsui K, Hishiyama S, Jain A, Kotoda Y, Abe M, Matsukawa T, Kotoda M.
Title Role of macrophage autophagy in postoperative pain and inflammation in mice.
Journal J Neuroinflammation
Abstract 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.
Volume 20(1)
Pages 102
Published 2023-5-2
DOI 10.1186/s12974-023-02795-w
PII 10.1186/s12974-023-02795-w
PMID 37131209
PMC PMC10152627
MeSH Animals Autophagy Inflammation* / metabolism Macrophages* / metabolism Mice Pain Threshold Pain, Postoperative / drug therapy
IF 5.793
Mice RBRC02302 RBRC02975