State Key Laboratory of Neuroscience, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Brain. 2012 Feb;135(Pt 2):391-403. doi: 10.1093/brain/awr350. Epub 2012 Jan 24.
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.
新出现的证据表明，伤害感受传入神经元释放的抑制性调节剂有助于疼痛调节。然而，背根神经节中小直径神经元中表达的抑制性调节剂仍有待进一步鉴定。本研究表明，表达于小直径背根神经节神经元中的激活素 C 对于抑制炎症诱导的伤害感受反应是必需的。在完全弗氏佐剂足底注射诱导的外周炎症早期，小直径背根神经节神经元中的激活素 C 表达明显下调。鞘内给予靶向激活素βC 的小干扰 RNA 或针对激活素 C 的抗体，可增强福尔马林诱导的伤害感受反应，并损害完全弗氏佐剂诱导的热痛觉过敏的恢复。鞘内给予激活素 C 可降低福尔马林或完全弗氏佐剂诱导的伤害感受反应。此外，发现激活素 C 可抑制背根神经节和背侧脊髓中炎症诱导的细胞外信号调节激酶磷酸化。因此，激活素 C 作为炎症性伤害感受传递的内源性抑制剂发挥作用，可能具有治疗炎症性疼痛的潜力。
