Tan Yi, Yang Jun, Xiang Kai, Tan Qindong, Guo Qulian
Department of Anesthesiology, Xiangya Hospital of Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, People's Republic of China.
Neurochem Res. 2015 Mar;40(3):550-60. doi: 10.1007/s11064-014-1500-2. Epub 2014 Dec 9.
Chronic neuropathic pain is an unfavourable pathological pain characterised by allodynia and hyperalgesia which has brought considerable trouble to people's physical and mental health, but effective therapeutics are still lacking. MicroRNAs (miRNAs) have been widely studied in the development of neuropathic pain and neuronal inflammation. Among various miRNAs, miR-155 has been widely studied. It is intensively involved in regulating inflammation-associated diseases. However, the role of miR-155 in regulating neuropathic pain development is poorly understood. In the present study, we aimed to investigate whether miR-155 is associated with neuropathic pain and delineate the underlying mechanism. Using a neuropathic pain model of chronic constriction injury (CCI), miR-155 expression levels were markedly increased in the spinal cord. Inhibition of miR-155 significantly attenuated mechanical allodynia, thermal hyperalgesia and proinflammatory cytokine expression. We also demonstrated that miR-155 directly bound with the 3'-untranslated region of the suppressor of cytokine signalling 1 (SOCS1). The expression of SOCS1 significantly decreased in the CCI rat model, but this effect could be reversed by miR-155 inhibition. Furthermore, knockdown of SOCS1 abrogated the inhibitory effects of miR-155 inhibition on neuropathic development and neuronal inflammation. Finally, we demonstrated that inhibition of miR-155 resulted in the suppression of nuclear factor-κB and p38 mitogen-activated protein kinase activation by mediating SOCS1. Our data demonstrate the critical role of miR-155 in regulating neuropathic pain through SOCS1, and suggest that miR-155 may be an important and potential target in preventing neuropathic pain development.
慢性神经病理性疼痛是一种以痛觉过敏和异常性疼痛为特征的不良病理性疼痛，给人们的身心健康带来了极大困扰，但目前仍缺乏有效的治疗方法。微小RNA（miRNA）在神经病理性疼痛和神经元炎症的发生发展中已得到广泛研究。在众多miRNA中，miR-155受到了广泛研究。它深入参与调控炎症相关疾病。然而，miR-155在调节神经病理性疼痛发展中的作用尚不清楚。在本研究中，我们旨在探究miR-155是否与神经病理性疼痛相关，并阐明其潜在机制。利用慢性压迫损伤（CCI）所致的神经病理性疼痛模型，发现脊髓中miR-155表达水平显著升高。抑制miR-155可显著减轻机械性痛觉过敏、热痛觉过敏和促炎细胞因子表达。我们还证明miR-155直接与细胞因子信号转导抑制因子1（SOCS1）的3'非翻译区结合。在CCI大鼠模型中，SOCS1的表达显著降低，但miR-155抑制可逆转这一效应。此外，敲低SOCS1可消除miR-155抑制对神经病理性疼痛发展和神经元炎症的抑制作用。最后，我们证明抑制miR-155可通过介导SOCS1抑制核因子-κB和p38丝裂原活化蛋白激酶的激活。我们的数据证明了miR-155通过SOCS1在调节神经病理性疼痛中的关键作用，并表明miR-155可能是预防神经病理性疼痛发展的一个重要且潜在的靶点。
