Microglial interleukin-1β in the ipsilateral dorsal horn inhibits the development of mirror-image contralateral mechanical allodynia through astrocyte activation in a rat model of inflammatory pain

被引：46

作者：

Choi, Hoon-Seong ^{[1
,2
]}

Roh, Dae-Hyun ^{[3
]}

Yoon, Seo-Yeon ^{[4
,5
]}

Moon, Ji-Young ^{[1
,2
]}

Choi, Sheu-Ran ^{[1
,2
]}

Kwon, Soon-Gu ^{[1
,2
]}

Kang, Suk-Yun ^{[6
]}

Han, Ho-Jae ^{[1
,2
]}

Kim, Hyun-Woo ^{[7
]}

Beitz, Alvin J. ^{[8
]}

Oh, Seog-Bae ^{[4
,5
]}

Lee, Jang-Herh ^{[1
,2
]}

机构：

[1] Seoul Natl Univ, Res Inst Vet Sci, Dept Vet Physiol, PLUS Program Creat Vet Sci Res BK21, Seoul 151742, South Korea

[2] Seoul Natl Univ, Coll Vet Med, Seoul 151742, South Korea

[3] Kyung Hee Univ, Sch Dent, Dept Maxillofacial Tissue Regenerat, Seoul, South Korea

[4] Seoul Natl Univ, Sch Dent, Dent Res Inst, Coll Nat Sci,Pain Cognit Funct Res Ctr,Dept Brain, Seoul 151742, South Korea

[5] Seoul Natl Univ, Sch Dent, Dept Neurobiol & Physiol, Seoul 151742, South Korea

[6] Korea Inst Oriental Med, Dept Acupuncture Moxibust & Meridian Res, Div Med Res, Taejon, South Korea

[7] Chungnam Natl Univ, Sch Med, Inst Brain Res, Dept Physiol, Taejon, South Korea

[8] Univ Minnesota, Coll Vet Med, Dept Vet & Biomed Sci, St Paul, MN 55108 USA

来源：

PAIN | 2015年 / 156卷 / 06期

基金：

新加坡国家研究基金会;

关键词：

Mirror-image pain; Microglia; Interleukin-1; beta; Astrocyte; GAP-JUNCTIONAL COMMUNICATION; SPINAL-CORD; NEUROPATHIC PAIN; GLIAL ACTIVATION; NERVE INJURY; INTRATHECAL INJECTION; CENTRAL SENSITIZATION; MURINE MODELS; TNF-ALPHA; P38; MAPK;

D O I：

10.1097/j.pain.0000000000000148

中图分类号：

R614 [麻醉学];

学科分类号：

100217 ;

摘要：

Damage on one side of the body can also result in pain on the contralateral unaffected side, called mirror-image pain (MIP). Currently, the mechanisms responsible for the development of MIP are unknown. In this study, we investigated the involvement of spinal microglia and interleukin-1 beta (IL-1 beta) in the development of MIP using a peripheral inflammatory pain model. After unilateral carrageenan injection, mechanical allodynia (MA) in both hind paws and the expression levels of spinal lba-1, IL-1 beta, and GFAP were evaluated. lpsilateral MA was induced beginning at 3 hours after carrageenan injection, whereas contralateral MA showed a delayed onset occurring 5 days after injection. A single intrathecal (it.) injection of minocycline, a tetracycline derivative that displays selective inhibition of microglial activation, or an interleukin-1 receptor antagonist (IL-1ra) on the day of carrageenan injection caused an early temporary induction of contralateral MA, whereas repeated i.t. treatment with these drugs from days 0 to 3 resulted in a long-lasting contralateral MA, which was evident in its advanced development. We further showed that IL-1 beta was localized to microglia and that minocycline inhibited the carrageenan-induced increases in spinal lba-1 and IL-1 beta expression. Conversely, minocycline or IL-1ra pretreatment increased GFAP expression as compared with that of control rats. However, it. pretreatment with fluorocitrate, an astrocyte inhibitor, restored minocycline- or IL-1ra-induced contralateral MA. These results suggest that spinal IL-1 beta derived from activated microglia temporarily suppresses astrocyte activation, which can ultimately prevent the development of contralateral MA under inflammatory conditions. These findings imply that microglial IL-1 beta plays an important role in regulating the induction of inflammatory MIP.

引用

页码：1046 / 1059

页数：14

共 67 条

[61] Early microglial inhibition preemptively mitigates chronic pain development after experimental spinal cord injury [J].