Gama Kelly Barbosa, Santos Dourivaldo Silva, Evangelista Afrânio Ferreira, Silva Daniela Nascimento, de Alcântara Adriano Costa, Dos Santos Ricardo Ribeiro, Soares Milena Botelho Pereira, Villarreal Cristiane Flora
Instituto Gonçalo Moniz, FIOCRUZ, Rua Waldemar Falcão 121, 40296-710 Salvador, BA, Brazil.
Faculdade de Farmácia, Universidade Federal da Bahia, Barão de Geremoabo s/n, 40170-290 Salvador, BA, Brazil.
Stem Cells Int. 2018 Jan 30;2018:8179013. doi: 10.1155/2018/8179013. eCollection 2018.
Neuropathic pain is a type of chronic pain caused by injury or dysfunction of the nervous system, without effective therapeutic approaches. Mesenchymal stromal cells (MSCs), through their paracrine action, have great potential in the treatment of this syndrome. In the present study, the therapeutic potential of MSC-derived conditioned medium (CM) was investigated in a mouse model of neuropathic pain induced by partial sciatic nerve ligation (PSL). PSL mice were treated by endovenous route with bone marrow-derived MSCs (1 × 10), CM, or vehicle. Gabapentin was the reference drug. Twelve hours after administration, neuropathic mice treated with CM exhibited an antinociceptive effect that was maintained throughout the evaluation period. MSCs also induced nonreversed antinociception, while gabapentin induced short-lasting antinociception. The levels of IL-1, TNF-, and IL-6 were reduced, while IL-10 was enhanced on sciatic nerve and spinal cord by treatment with CM and MSCs. Preliminary analysis of the CM secretome revealed the presence of growth factors and cytokines likely involved in the antinociception. In conclusion, the CM, similar to injection of live cells, produces a powerful and long-lasting antinociceptive effect on neuropathic pain, which is related with modulatory properties on peripheral and central levels of cytokines involved with the maintenance of this syndrome.
神经性疼痛是一种由神经系统损伤或功能障碍引起的慢性疼痛，目前尚无有效的治疗方法。间充质基质细胞（MSCs）通过其旁分泌作用，在治疗该综合征方面具有巨大潜力。在本研究中，我们在部分坐骨神经结扎（PSL）诱导的神经性疼痛小鼠模型中研究了MSC来源的条件培养基（CM）的治疗潜力。通过静脉途径用骨髓来源的MSCs（1×10）、CM或赋形剂治疗PSL小鼠。加巴喷丁为参比药物。给药12小时后，用CM治疗的神经性疼痛小鼠表现出抗伤害感受作用，且在整个评估期内持续存在。MSCs也诱导了不可逆的抗伤害感受，而加巴喷丁诱导了短暂的抗伤害感受。通过CM和MSCs治疗，坐骨神经和脊髓中IL-1、TNF-和IL-6水平降低，而IL-10水平升高。对CM分泌组的初步分析显示存在可能与抗伤害感受有关的生长因子和细胞因子。总之，CM与注射活细胞相似，对神经性疼痛产生强大而持久的抗伤害感受作用，这与对参与维持该综合征的外周和中枢水平细胞因子的调节特性有关。
