Brain：张旭等在痛觉调节的研究中取得新成果

近日，国际著名杂志《脑》Brain在线刊登了中科院上海生命科学研究院神经所张旭研究组的最新研究成果“Activin C expressed in nociceptive afferent neurons is required for suppressing inflammatory pain，”，文章中，研究者在活化素C参与调控急性和慢性炎性痛的研究上取得了重要成果。

活化素家族（activin）是转化生长因子-β（transforming growth factor-β，TGF-β）超家族之一，关于该超家族成员在参与调控疼痛方面的功能越来越受到重视。位于背根神经节（DRG）中的初级感觉神经元在痛觉的产生和传导过程中起重要作用。在这项研究中，研究人员首先制作了包含了TGF-β超家族中多个家族的多个生长因子、受体、信号调节蛋白、靶基因及其相关分子的基因芯片，并应用此基因芯片在慢性炎性痛大鼠模型的DRG中筛选有显著表达改变的分子。

科研人员应用基因芯片筛选、生化和免疫组化等方法，发现参与痛觉调节的小神经元表达activin C，在慢性炎性痛大鼠的DRG中activin C的表达显著下调。鞘内注射activin C可以显著抑制急性和慢性疼痛，注射该细胞因子的抗体或用干扰RNA阻断activin C的功能都明显增强了疼痛。这表明该分子在调控慢性炎性痛中起重要作用。

进一步的研究表明，activin C是通过抑制多种致炎因子引起的ERK信号通路的激活而发挥镇痛作用的。这项研究为镇痛药的研发提供了新线索。

该课题由博士后刘兴君及其合作者张方雄等在张旭研究员指导下完成，得到了中国科学院、科技部、国家自然科学基金委和中国博士后基金会等的支持。（生物谷Bioon.com）

doi:10.1093/brain/awr350
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Activin C expressed in nociceptive afferent neurons is required for suppressing inflammatory pain

Xing-Jun Liu1, Fang-Xiong Zhang1, Hui Liu1, Kai-Cheng Li1, Ying-Jin Lu1, Qing-Feng Wu1, Jia-Yin Li1, Bin Wang2, Qiong Wang2, Li-Bo Lin3, Yan-Qing Zhong1, Hua-Sheng Xiao3, Lan Bao2 and Xu Zhang1

Emerging evidence suggests that the suppressive modulators released from nociceptive afferent neurons contribute to pain regulation. However, the suppressive modulators expressed in small-diameter neurons of the dorsal root ganglion remain to be further identified. The present study shows that the activin C expressed in small dorsal root ganglion neurons is required for suppressing inflammation-induced nociceptive responses. The expression of activin C in small dorsal root ganglion neurons of rats was markedly downregulated during the early days of peripheral inflammation induced by intraplantar injection of the complete Freund's adjuvant. Intrathecal treatment with the small interfering RNA targeting activin βC or the antibodies against activin C could enhance the formalin-induced nociceptive responses, and impair the recovery from the complete Freund's adjuvant-induced thermal hyperalgesia. Intrathecally applied activin C could reduce nociceptive responses induced by formalin or complete Freund's adjuvant. Moreover, activin C was found to inhibit the inflammation-induced phosphorylation of extracellular signal-regulated kinase in the dorsal root ganglia and the dorsal spinal cord. Thus, activin C functions as an endogenous suppressor of inflammatory nociceptive transmission and may have a therapeutic potential for treatment of inflammatory pain.