title: The role of spinal interleukin-1β and astrocyte connexin 43 in the development of mirror-image pain in an inflammatory pain model.
abstract: Although we have recently demonstrated that carrageenan-induced inflammation upregulates the expression of spinal interleukin (IL)-1β, which inhibits spinal astrocyte activation and results in the delayed development of Mirror-Image Pain (MIP), little is known regarding the mechanisms that underlie how spinal IL-1β inhibits the astrocyte activation. In this study, we examined the effect of spinal IL-1β on astrocyte gap junctions (GJ) and the development of MIP. Following unilateral carrageenan (CA) injection, mechanical allodynia (MA) was evaluated at various time points. Immunohistochemistry and Western blot analysis were used to determine changes in the expression of GFAP and connexins (Cx) in the spinal cord dorsal horn. Carrageenan rats showed a delayed onset of contralateral MA, which mimicked the temporal expression pattern of spinal Cx43 (an astrocyte gap junctional protein) and GFAP. Intrathecal administration of an interleukin-1 receptor antagonist (IL-1ra) twice-a-day on post-carrageenan injection days 0 to 3 caused a significant increase in contralateral MA and spinal Cx43 and GFAP expression. In addition, co-administration of IL-1β with IL-1ra blocked the IL-1ra-induced increase in contralateral MA and the upregulated expression of spinal Cx43 and GFAP. Finally, co-administration of carbenoxolone (CBX; a GJ decoupler) or Gap26 (a specific Cx43 mimetic blocking peptide) with IL-1ra significantly blocked the IL-1ra-induced early development of contralateral MA and the associated upregulation of spinal Cx43 and GFAP expression. These results demonstrate that spinal IL-1β suppresses Cx43 expression and astrocyte activation during the early phase of CA-induced inflammation resulting in the delayed onset of contralateral MA. These findings imply that spinal IL-1β can inhibit astrocyte activation and regulate the time of induction of contralateral MA through modulation of spinal Cx43 expression.
authors: Department of Veterinary Physiology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors: Hoon-Seong
authors: HS
authors: Choi
authors: Department of Oral Physiology, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors: Dae-Hyun
authors: DH
authors: Roh
authors: Pain Cognitive Function Research Center, Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Seo-Yeon
authors: SY
authors: Yoon
authors: Department of Oral Physiology, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors: Soon-Gu
authors: SG
authors: Kwon
authors: Department of Veterinary Physiology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors: Sheu-Ran
authors: SR
authors: Choi
authors: KM Fundamental Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea.
authors: Suk-Yun
authors: SY
authors: Kang
authors: KM Fundamental Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea.
authors: Ji-Young
authors: JY
authors: Moon
authors: Department of Veterinary Physiology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors: Ho-Jae
authors: HJ
authors: Han
authors: Department of Physiology, Institute of Brain Research, Chungnam National University Medical School, Daejeon, Republic of Korea.
authors: Hyun-Woo
authors: HW
authors: Kim
authors: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, MN, USA.
authors: Alvin J
authors: AJ
authors: Beitz
authors: Department of Veterinary Physiology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea. Electronic address: jhl1101@snu.ac.kr.
authors: Jang-Hern
authors: JH
authors: Lee
keywords: Astrocyte; Connexin 43; Interleukin-1ß; Mirror-image pain