Pharmacological blockade of cannabinoid type II receptors and mesenchymal stem cell transplantation in a model of peripheral neuropathic pain

A.-M. V. Yerofeyeva, S. Pinchuk, S. Rjabceva, A. Molchanova
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Abstract

Objective. To evaluate the anti-nociceptive and reparative effects of adipose-derived mesenchymal stem cells (ADMSCs) under the pharmacological blockade of cannabinoid CB2 receptors in a model of peripheral neuropathic pain.Material and methods. In 40 male Wistar rats, modeling of peripheral neuropathy (NP) was performed by excising a sciatic nerve. On day 7 of the study, ADMSCs (1 × 106 cells/kg) were transplanted into the area of sciatic nerve injury without additional influences or after administration of the CB2 receptor antagonist AM630, as well as after incubation with AM630. Within 90  days, nociceptive sensitivity was studied, as well as a detailed analysis of gait using CatWalk XT (Noldus, Netherlands). On day 21 and day 90, histostructure of the distal segment of the sciatic nerve was assessed.Results. Pharmacological blockade of CB2 receptors both on the ADMSCs and in the soft tissues surrounding the site of sciatic nerve injury led to a decrease in withdrawal threshold and withdrawal latency from day 28 of the study compared with the group of rats with NP and transplantation of ADMSCs only. Local injection of AM630 before transplantation of ADMSCs contributed to the development of  NP-induced gait disturbances and increase of the number of damaged nerve fibers in the distal segment of sciatic nerve. Transplantation of ADMSCs pretreated with  AM630 did not significantly affect the rate of recovery of gait parameters, and decreased the number of damaged nerve fibers by day 90 of study.Conclusion. Blockade of CB2 receptors, both on the membranes of MSCs and in the area of damage to the peripheral nerve, has a negative effect on the development of the anti-nociceptive and reparative effects of MSCs.
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药理阻断大麻素 II 型受体和间充质干细胞移植在外周神经病理性疼痛模型中的应用
目的评估脂肪间充质干细胞(ADMSCs)在周围神经病理性疼痛模型中,在大麻素 CB2 受体药理阻断作用下的抗痛觉和修复作用。在40只雄性Wistar大鼠中,通过切除坐骨神经建立周围神经病变(NP)模型。在研究的第 7 天,将 ADMSCs(1 × 106 cells/kg)移植到坐骨神经损伤区域,不施加额外影响,或在施用 CB2 受体拮抗剂 AM630 后,以及在与 AM630 一起孵育后移植。在 90 天内,对痛觉敏感性进行了研究,并使用 CatWalk XT(荷兰 Noldus 公司)对步态进行了详细分析。第 21 天和第 90 天,对坐骨神经远端组织结构进行了评估。与仅移植 ADMSCs 的 NP 组大鼠相比,药物阻断 ADMSCs 上和坐骨神经损伤部位周围软组织中的 CB2 受体可降低戒断阈值和戒断潜伏期。移植ADMSCs前局部注射AM630有助于NP引起的步态障碍的发展和坐骨神经远段受损神经纤维数量的增加。用AM630预处理的ADMSCs移植并没有明显影响步态参数的恢复速度,到研究的第90天,受损神经纤维的数量也有所减少。间充质干细胞膜上和周围神经损伤区域的 CB2 受体阻断对间充质干细胞抗痛觉和修复作用的发展有负面影响。
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