近日,，國際著名雜志《腦》Brain在線刊登了中科院上海生命科學研究院神經所張旭研究組的最新研究成果“Activin C expressed in nociceptive afferent neurons is required for suppressing inflammatory pain，”,，文章中,，研究者在活化素C參與調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）是轉化生長因子-β（transforming growth factor-β,，TGF-β）超家族之一,，關于該超家族成員在參與調控疼痛方面的功能越來越受到重視。位于背根神經節(jié)（DRG）中的初級感覺神經元在痛覺的產生和傳導過程中起重要作用,。在這項研究中,，研究人員首先制作了包含了TGF-β超家族中多個家族的多個生長因子、受體,、信號調節(jié)蛋白,、靶基因及其相關分子的基因芯片，并應用此基因芯片在慢性炎性痛大鼠模型的DRG中篩選有顯著表達改變的分子,。
科研人員應用基因芯片篩選、生化和免疫組化等方法,，發(fā)現參與痛覺調節(jié)的小神經元表達activin C,，在慢性炎性痛大鼠的DRG中activin C的表達顯著下調。鞘內注射activin C可以顯著抑制急性和慢性疼痛,，注射該細胞因子的抗體或用干擾RNA阻斷activin C的功能都明顯增強了疼痛,。這表明該分子在調控慢性炎性痛中起重要作用。
進一步的研究表明,，activin C是通過抑制多種致炎因子引起的ERK信號通路的激活而發(fā)揮鎮(zhèn)痛作用的,。這項研究為鎮(zhèn)痛藥的研發(fā)提供了新線索。
該課題由博士后劉興君及其合作者張方雄等在張旭研究員指導下完成,，得到了中國科學院,、科技部、國家自然科學基金委和中國博士后基金會等的支持,。（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.
