Bannerman Courtney A, Douchant Katya, Segal Julia P, Knezic Mitra, Mack Alexandra E, Lundell-Creagh Caitlin, Silva Jaqueline R, Duggan Scott, Sheth Prameet, Ghasemlou Nader
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
Division of Microbiology, Kingston Health Sciences Centre, Kingston, ON, Canada.
Pain. 2022 Jun 1;163(6):1172-1185. doi: 10.1097/j.pain.0000000000002471. Epub 2021 Aug 30.
Chronic pain is a common medical complication experienced by those living with spinal cord injury (SCI) and leads to worsened quality of life. The pathophysiology of SCI pain is poorly understood, hampering the development of safe and efficacious therapeutics. We therefore sought to develop a clinically relevant model of SCI with a strong pain phenotype and characterize the central and peripheral pathology after injury. A contusion (50 kdyn) injury, with and without sustained compression (60 seconds) of the spinal cord, was performed on female C57BL/6J mice. Mice with compression of the spinal cord exhibited significantly greater heat and mechanical hypersensitivity starting at 7 days postinjury, concomitant with reduced locomotor function, compared with those without compression. Immunohistochemical analysis of spinal cord tissue revealed significantly less myelin sparing and increased macrophage activation in mice with compression compared with those without. As measured by flow cytometry, immune cell infiltration and activation were significantly greater in the spinal cord (phagocytic myeloid cells and microglia) and dorsal root ganglia (Ly6C+ monocytes) after compression injury. We also decided to investigate the gastrointestinal microbiome, as it has been shown to be altered in patients with SCI and has recently been shown to play a role in immune system maturation and pain. We found increased dysbiosis of the gastrointestinal microbiome in an injury severity-dependent manner. The use of this contusion-compression model of SCI may help advance the preclinical assessment of acute and chronic SCI pain and lead to a better understanding of mechanisms contributing to this pain.
慢性疼痛是脊髓损伤（SCI）患者常见的医学并发症，会导致生活质量下降。SCI疼痛的病理生理学尚不清楚，这阻碍了安全有效的治疗方法的开发。因此，我们试图建立一种具有强烈疼痛表型的临床相关SCI模型，并对损伤后的中枢和外周病理学特征进行描述。对雌性C57BL/6J小鼠进行挫伤（50千达因）损伤，部分伴有脊髓持续压迫（60秒）。与未受压的小鼠相比，脊髓受压的小鼠在损伤后7天开始表现出明显更强的热超敏反应和机械超敏反应，同时运动功能下降。脊髓组织的免疫组织化学分析显示，与未受压的小鼠相比，受压小鼠的髓鞘保留明显减少，巨噬细胞活化增加。通过流式细胞术测量，受压损伤后脊髓（吞噬性髓样细胞和小胶质细胞）和背根神经节（Ly6C+单核细胞）中的免疫细胞浸润和活化明显增加。我们还决定研究胃肠道微生物群，因为已证明SCI患者的胃肠道微生物群会发生改变，并且最近已证明其在免疫系统成熟和疼痛中起作用。我们发现胃肠道微生物群的失调以损伤严重程度依赖的方式增加。使用这种SCI挫伤-压迫模型可能有助于推进急性和慢性SCI疼痛的临床前评估，并有助于更好地理解导致这种疼痛的机制。
