■脊髓损伤(SCI)引起的疼痛给患者带来了巨大负担,疼痛管理正在成为治疗的重点。很少有报道描述SCI后大脑的变化。特别是,脑区影响伤后疼痛的确切机制尚不清楚.在这项研究中,我们旨在确定疼痛的潜在治疗机制。建立脊髓挫伤小鼠模型,在SCI部位局部注射人脐带间充质干细胞(HU-MSCs)后,观察了大脑中前扣带回皮质(ACC)和导水管周围灰质(PAG)的分子表达和动物行为。
■将63只雌性C57BL/6J小鼠分为4组:假手术组(n=15);脊髓损伤组(SCI,n=16);SCI+HU-MSCs组(n=16)和SCI+PBS组(n=16),其中SCI位点注射HU-MSC/磷酸盐缓冲液。确定了BMS评分,术后每周使用vonFrey测试和Hargreaves测试评估行为。术后第4周处死小鼠,并收集样本。CGRP的表达,物质P,免疫组化观察ACC和PAG中的C-Fos和KCC2。铬花青染色用于观察受损脊髓的横切面。
■在SCI后的ACC和PAG中,CGRP的表达,SP和C-Fos增加,KCC2的表达下降,而在HU-MSC注射后,CGRP的表达,SP和C-Fos下降,KCC2的表达增加。SCI+HU-MSC组术后2~4周的运动能力优于SCI/SCI+PBS组(P<0.001)。术后第4周局部注射HU-MSCs可显著改善SCI引起的机械性痛觉过敏(P<0.0001),术后2周感觉明显恢复(P<0.0001);热超敏反应无改善(P>0.05)。HU-MSC组比SCI/SCI+PBS组保留更多的白质(P<0.0001)。
■在SCI部位局部移植HU-MSCs可部分缓解神经性疼痛并促进运动功能恢复。这些发现为未来SCI的治疗提供了可行的方向。
UNASSIGNED: The pain caused by spinal cord injury (SCI) poses a major burden on patients, and pain management is becoming a focus of treatment. Few reports have described changes in the brain after SCI. Particularly, the exact mechanism through which brain regions affect post-injury pain remains unclear. In this study, we aimed to determine the potential therapeutic mechanisms of pain. A mouse model of spinal cord contusion was established, and molecular expression in the anterior cingulate cortex (ACC) and periaqueductal gray (PAG) in the brain and animal behavior was observed after local injection of human umbilical cord mesenchymal stem cells (HU-MSCs) at the site of SCI.
UNASSIGNED: Sixty-three female C57BL/6J mice were divided into four groups: a sham operation group (n = 15); a spinal injury group (SCI, n = 16); an SCI + HU-MSCs group (n = 16) and an SCI + PBS group (n = 16), in which the SCI site was injected with HU-MSCs/phosphate buffer. The BMS score was determined, and the von Frey test and Hargreaves test were used to assess behavior every week after surgery. Mice were sacrificed in the fourth week after operation, and samples were collected. The expression of CGRP, Substance P, C-Fos and KCC2 in the ACC and PAG were observed with immunohistochemistry. Chromic cyanine staining was used to observe transverse sections of the injured spinal cord.
UNASSIGNED: In the ACC and PAG after SCI, the expression of CGRP, SP and C-Fos increased, and the expression of KCC2 decreased, whereas after HU-MSC injection, the expression of CGRP, SP and C-Fos decreased, and the expression of KCC2 increased. The SCI + HU-MSC group showed better exercise ability from 2 to 4 weeks after surgery than the SCI/SCI + PBS groups (P < 0.001). Local injection of HU-MSCs significantly improved the mechanical hyperalgesia caused by SCI in the fourth week after surgery (P < 0.0001), and sensation was significantly recovered 2 weeks after surgery (P < 0.0001); no improvement in thermal hypersensitivity was observed (P > 0.05). The HU-MSC group retained more white matter than the SCI/SCI + PBS groups (P < 0.0001).
UNASSIGNED: Local transplantation of HU-MSCs at the site of SCI partially relieves the neuropathic pain and promotes recovery of motor function. These findings suggest a feasible direction for the future treatment of SCI.