Development and validation of a mouse model to investigate post surgical pain after laparotomy

IF 1.4 Q3 SURGERY Surgery open science Pub Date : 2024-06-18 DOI:10.1016/j.sopen.2024.06.002
Juan Martinez , Thomas Maisey , Nicola Ingram , Nikil Kapur , Paul A. Beales , David G. Jayne
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Abstract

Background

Postoperative pain following abdominal surgery is a significant obstacle to patient recovery, often necessitating high analgesic doses associated with adverse effects like cognitive impairment and cardiorespiratory depression. Reliable animal models are crucial for understanding the pathophysiology of post surgical pain and developing more effective pain-relieving strategies.

Methods

We developed a mouse model to replicate peritoneal trauma induced by abdominal surgery. 30 C57BL/6 mice underwent laparotomy, with half undergoing standardised peritoneal abrasion and the rest serving as controls. Mouse recovery was assessed using two validated scoring systems of surgical recovery: Post surgery Severity Assessment (PSSA) and Mouse Grimace Score (MGS). Blood samples were taken for cytokine analysis. Adhesions were evaluated on day 6, and peritoneal tissue was examined for healing markers.

Results

After laparotomy, all mice exhibited expected pain profiles. Mice with peritoneal abrasion had significantly higher PSSA (7.2 ± 1.2 vs 4.68 ± 0.82, p ≤ 0.001) and MGS scores (3.62 ± 0.74 vs 0.82 ± 0.40, p ≤ 0.05) with slower recovery. Serum inflammatory cytokine levels were significantly elevated in the abraded group, and adhesion formation was higher in this group. Immunohistochemical analysis showed significantly increased expression of α-SMA, CD31, CD68, and F4/80 in peritoneal tissue in the abraded group.

Discussion

A mouse model involving laparotomy and standardised peritoneal abrasion replicates the expected pathophysiological changes following abdominal surgery. It will be a useful model for better understanding the mechanisms of post surgical pain and developing improved pain-relief strategies. It also has utility for the study of intra-abdominal adhesion formation.

Key message

To understand the intricate relationship between peritoneal trauma-induced pain, cytokine response, and post-operative adhesion formation in mouse models for advancing therapeutic interventions and enhancing post-operative recovery outcomes.

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开发和验证小鼠模型以研究开腹手术后的疼痛
背景腹部手术后疼痛是患者康复的一大障碍,通常需要使用大剂量镇痛药,并伴有认知障碍和心肺功能抑制等不良反应。可靠的动物模型对于了解手术后疼痛的病理生理学和开发更有效的止痛策略至关重要。30 只 C57BL/6 小鼠接受了开腹手术,其中一半接受了标准化腹膜擦伤,其余作为对照组。小鼠的恢复情况采用两种经过验证的手术恢复评分系统进行评估:术后严重程度评估(PSSA)和小鼠痛苦评分(MGS)。采集血液样本用于细胞因子分析。第 6 天对粘连进行评估,并检查腹膜组织的愈合标记物。腹膜擦伤小鼠的 PSSA(7.2 ± 1.2 vs 4.68 ± 0.82,p ≤ 0.001)和 MGS 评分(3.62 ± 0.74 vs 0.82 ± 0.40,p ≤ 0.05)明显较高,且恢复较慢。擦伤组的血清炎症细胞因子水平明显升高,粘连形成也更高。免疫组化分析显示,磨损组腹膜组织中 α-SMA、CD31、CD68 和 F4/80 的表达明显增加。它将成为一种有用的模型,有助于更好地了解手术后疼痛的机制,并开发出更好的止痛策略。关键信息了解小鼠模型中腹膜创伤引起的疼痛、细胞因子反应和术后粘连形成之间错综复杂的关系,以促进治疗干预和提高术后恢复效果。
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来源期刊
CiteScore
1.30
自引率
0.00%
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审稿时长
66 days
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