Inhibition of ROS-induced p38MAPK and ERK activation in microglia by acupuncture relieves neuropathic pain after spinal cord injury in rats

被引:158
作者
Choi, Doo C. [2 ,3 ]
Lee, Jee Y. [2 ,3 ]
Lim, Eun J. [2 ,3 ]
Baik, Hyung H. [1 ]
Oh, Tae H. [2 ]
Yune, Tae Y. [1 ,2 ,3 ]
机构
[1] Kyung Hee Univ, Dept Biochem & Mol Biol, Sch Med, Seoul 130701, South Korea
[2] Kyung Hee Univ, Age Related & Brain Dis Res Ctr, Sch Med, Seoul 130701, South Korea
[3] Kyung Hee Univ, Neurodegenerat Control Res Ctr, Sch Med, Seoul 130701, South Korea
基金
新加坡国家研究基金会;
关键词
Acupuncture; Spinal cord injury; Central neuropathic pain; Microglia; MAPK kinase; Prostaglandin E2; PERIPHERAL-NERVE INJURY; SUPERFICIAL DORSAL-HORN; PRO-INFLAMMATORY CYTOKINES; STRESS-INDUCED ANALGESIA; RECEPTOR UP-REGULATION; MECHANICAL ALLODYNIA; INTRATHECAL MORPHINE; FUNCTIONAL RECOVERY; PROSTAGLANDIN E-2; CELL-DEATH;
D O I
10.1016/j.expneurol.2012.05.014
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Acupuncture (AP) is currently used worldwide to relieve pain. However, little is known about its mechanisms of action. We found that after spinal cord injury (SCI). AP inhibited the production of superoxide anion (O-2 center dot). which acted as a modulator for microglial activation, and the analgesic effect of AP was attributed to its anti-microglial activating action. Direct injection of a ROS scavenger inhibited SCI-induced NP. After contusion injury which induces the below-level neuropathic pain (NP), Shuigou and Yanglingquan acupoints were applied. AP relieved mechanical allodynia and thermal hyperalgesia, while vehicle and simulated AP did not. AP also decreased the proportion of activated microglia, and inhibited both p38MAPK and ERK activation in microglia at the L4-5. Also, the level of prostaglandin E-2 (PGE2), which is produced via ERK signaling and mediates the below-level pain through PGE2 receptor, was reduced by AP. Injection of p38MAPK or ERK inhibitors attenuated NP and decreased PGE2 production. Furthermore, ROS produced after injury-induced p38MAPK and ERK activation in microglia, and mediated mechanical allodynia and thermal hyperalgesia, which were inhibited by AP or a ROS scavenger. AP also inhibited the expression of inflammatory mediators. Therefore, our results suggest that the analgesic effect of AP may be partly mediated by inhibiting ROS-induced microglial activation and inflammatory responses after SCI and provide the possibility that AP can be used effectively as a non-pharmacological intervention for SCI-induced chronic NP in patients. (C) 2012 Published by Elsevier Inc.
引用
收藏
页码:268 / 282
页数:15
相关论文
共 71 条
[21]   Characterization of chronic pain and somatosensory function in spinal cord injury subjects [J].
Defrin, R ;
Ohry, A ;
Blumen, N ;
Urca, G .
PAIN, 2001, 89 (2-3) :253-263
[22]   Remote activation of microglia and pro-inflammatory cytokines predict the onset and severity of below-level neuropathic pain after spinal cord injury in rats [J].
Detloff, Megan Ryan ;
Fisher, Lesley C. ;
McGaughy, Violetta ;
Longbrake, Erin E. ;
Popovich, Phillip G. ;
Basso, D. Michele .
EXPERIMENTAL NEUROLOGY, 2008, 212 (02) :337-347
[23]   Pathophysiological mechanisms of central neuropathic pain after spinal cord injury [J].
Eide, PK .
SPINAL CORD, 1998, 36 (09) :601-612
[24]   Pain and dysesthesia in patients with spinal cord injury: A postal survey [J].
Finnerup, NB ;
Johannesen, IL ;
Sindrup, SH ;
Bach, FW ;
Jensen, TS .
SPINAL CORD, 2001, 39 (05) :256-262
[25]   Clinical correlates of stress-induced analgesia: Evidence from pharmacological studies [J].
Ford, Gemma K. ;
Finn, David P. .
PAIN, 2008, 140 (01) :3-7
[26]   Chronic blockade of interleukin-1 (IL-1) prevents and attenuates neuropathic pain behavior and spontaneous ectopic neuronal activity following nerve injury [J].
Gabay, Eran ;
Wolf, Gilly ;
Shavit, Yehuda ;
Yirmiya, Raz ;
Tal, Michael .
EUROPEAN JOURNAL OF PAIN, 2011, 15 (03) :242-248
[27]   Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture [J].
Goldman, Nanna ;
Chen, Michael ;
Fujita, Takumi ;
Xu, Qiwu ;
Peng, Weiguo ;
Liu, Wei ;
Jensen, Tina K. ;
Pei, Yong ;
Wang, Fushun ;
Han, Xiaoning ;
Chen, Jiang-Fan ;
Schnermann, Jurgen ;
Takano, Takahiro ;
Bekar, Lane ;
Tieu, Kim ;
Nedergaard, Maiken .
NATURE NEUROSCIENCE, 2010, 13 (07) :883-U130
[28]   Long-term actions of interleukin-1β on delay and tonic firing neurons in rat superficial dorsal horn and their relevance to central sensitization [J].
Gustafson-Vickers, Sabrina L. ;
Lu, Van B. ;
Lai, Aaron Y. ;
Todd, Kathryn G. ;
Ballanyi, Klaus ;
Smith, Peter A. .
MOLECULAR PAIN, 2008, 4
[29]   Activated microglia contribute to the maintenance of chronic pain after spinal cord injury [J].
Hains, BC ;
Waxman, SG .
JOURNAL OF NEUROSCIENCE, 2006, 26 (16) :4308-4317
[30]   Reduction of pathological and behavioral deficits following spinal cord contusion injury with the selective cyclooxygenase-2 inhibitor NS-398 [J].
Hains, BC ;
Yucra, JA ;
Hulsebosch, CE .
JOURNAL OF NEUROTRAUMA, 2001, 18 (04) :409-423