Nociceptive sensitization by complement C5a and C3a in mouse.
Nociceptive sensitization by complement C5a and C3a in mouse.
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DOI：
10.1016/j.pain.2009.11.021
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发表时间：
2010-02
期刊：
影响因子：
7.4
通讯作者：
Brennan TJ
中科院分区：
文献类型：
--
作者：
Jang JH;Clark DJ;Li X;Yorek MS;Usachev YM;Brennan TJ
损伤激活补体系统通过产生能够招募和激活免疫细胞的补体片段C5a和C3a而增加炎症。补体激活可能有助于炎症和损伤后的疼痛。在本研究中，我们检测了C5a和C3a在体内注射到小鼠后爪时是否会引起伤害感受，以及C5a和C3a在体外外周末梢注射时是否会激活和/或致敏机械敏感的伤害感受受体。我们还使用Ca2+成像技术检测了背根神经节（DRG）中C5a受体（C5aR） mRNA的表达以及C5a和C3a对细胞内Ca2+浓度（[Ca2+]i）的影响。足底注射C5a引起热痛觉过敏，C5a和C3a引起机械痛觉过敏。暴露于C5a或C3a后，c -伤害感受器对热敏感，热反应纤维比例增加，热反应阈值降低，热刺激期间和之后的动作电位增加。a -伤害感受器被补体激活。然而，应用C5a和C3a后，A-和C-伤害感受器的机械反应没有变化。在DRG中检测到C5aR mRNA的存在。C5a和C3a的应用提高了[Ca2+]i，促进了辣椒素诱导的DRG神经元[Ca2+]i反应。结果表明补体片段C5a和C3a可能通过激活和增敏皮肤伤害感受器而参与伤害感受。
Activation of the complement system by injury increases inflammation by producing complement fragments C5a and C3a which are able to recruit and activate immune cells. Complement activation may contribute to pain after inflammation and injury. In the present study, we examined whether C5a and C3a elicit nociception when injected into mouse hind paws in vivo, and whether C5a and C3a activate and/or sensitize mechanosensitive nociceptors when applied on peripheral terminals in vitro. We also examined the dorsal root ganglia (DRG) for C5a receptor (C5aR) mRNA and effects of C5a and C3a on intracellular Ca2+ concentration ([Ca2+]i) using Ca2+ imaging. Heat hyperalgesia was elicited by intraplantar injection of C5a, and mechanical hyperalgesia by C5a and C3a. After exposure to either C5a or C3a, C-nociceptors were sensitized to heat as evidenced by an increased proportion of heat responsive fibers, lowered response threshold to heat and increased action potentials during and after heat stimulation. A-nociceptors were activated by complement. However, no change was observed in mechanical responses of A- and C- nociceptors after C5a and C3a application. The presence of C5aR mRNA was detected in DRG. C5a and C3a application elevated [Ca2+]i and facilitated capsaicin-induced [Ca2+]i responses in DRG neurons. The results suggest a potential role for complement fragments C5a and C3a in nociception by activating and sensitizing cutaneous nociceptors.
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DOI：
10.1523/jneurosci.3795-08.2008
发表时间：
2008-12-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Binshtok AM;Wang H;Zimmermann K;Amaya F;Vardeh D;Shi L;Brenner GJ;Ji RR;Bean BP;Woolf CJ;Samad TA
通讯作者：
Samad TA
影响因子：
8.8
作者：
Clark, J. David;Qiao, Yanli;Yeomans, David C.
通讯作者：
Yeomans, David C.
影响因子：
3.3
作者：
CHOLEWINSKI, A;BURGESS, GM;BEVAN, S
通讯作者：
BEVAN, S
影响因子：
7.3
作者：
CUNHA, FQ;POOLE, S;FERREIRA, SH
通讯作者：
FERREIRA, SH
DOI：
10.1016/0167-5699(91)90009-i
发表时间：
1991-09-01
期刊：
IMMUNOLOGY TODAY
影响因子：
--
作者：
FRANK, MM;FRIES, LF
通讯作者：
FRIES, LF