Involvement of peripheral P2Y1 receptors and potential interaction with IL-1 receptors in IL-1β-induced thermal hypersensitivity in rats.
Although interleukin-1β (IL-1β) is a prototypical pro-inflammatory cytokine, the specific mechanisms underlying the role of its cognate receptor, the interleukin-1 receptor (IL-1R) in peripheral sensitization remain to be investigated. Since emerging evidence in the literature indicates that IL-1β can modulate membrane-bound receptors, we decided to examine the involvement of P2Y1 receptor (P2Y1R) in IL-1β induced pain and the potential interaction of P2Y1Rs and IL-1Rs in both naïve and carrageenan injected rats. Intraplantar (i.pl) injection of IL-1β dose-dependently produced mechanical and thermal hypersensitivity in naïve rats. Pre-treatment with IL-1ra (i.pl, 30 and 100ng), an endogenous IL-1R antagonist, prevented the IL-1β induced mechanical and thermal hypersensitivity. Pre-treatment with MRS2500 (i.pl, 1 and 3nmol), a specific P2Y1R antagonist, dose-dependently reduced IL-1β induced thermal hypersensitivity, but did not affect the development of mechanical hypersensitivity. Conversely coadministration of MRS2500 (i.pl, 0.1nmol, sub-effective dose) together with IL-1ra (10nmol, sub-effective dose) significantly reduced IL-1β induced thermal, but not mechanical hypersensitivity. We next used immunohistochemistry to demonstrate that P2Y1 and IL-1 type I receptors co-localize predominantly in small diameter neurons in the dorsal root ganglion. We also performed experiments to examine the interaction of P2Y1Rs and IL-1Rs under the inflammatory conditions induced by 2% carrageenan. Intraplantar coadministration of MRS2500 (3nmol, sub-effective dose) and IL-1ra (30ng, sub-effective dose) significantly reduced inflammatory thermal, but not mechanical, hypersensitivity. These data indicate the involvement of P2Y1Rs in IL-1β mediated pain in both naive and carrageenan injected rats. There is a positive interaction between peripheral P2Y1Rs and IL-1Rs in both IL-1β and carrageenan-induced thermal hypersensitivity.
Neuracle Science Co. Ltd., Seoul 02841, Republic of Korea.
Soon-Gu
SG
Kwon
Department of Maxillofacial Tissue Regeneration, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
Dae-Hyun
DH
Roh
Pain Cognitive Function Research Center, Department of Brain and Cognitive Sciences, College of Natural Sciences, Dental Research Institute, Department of Neurobiology and Physiology, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
Seo-Yeon
SY
Yoon
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.
Sheu-Ran
SR
Choi
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.
Hoon-Seong
HS
Choi
KM Fundamental Research Division, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea.
Ji-Young
JY
Moon
KM Fundamental Research Division, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea.
Suk-Yun
SY
Kang
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA.
Alvin J
AJ
Beitz
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.
Jang-Hern
JH
Lee
D000818:Animals; D002351:Carrageenan / Q000008:administration & dosage; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000502:physiology*; D008297:Male; D017288:Pain Threshold; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000502:physiology*; D058472:Receptors, Purinergic P2Y1 / Q000502:physiology*
C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1; D058472:Receptors, Purinergic P2Y1; D002351:Carrageenan
Inflammation; Interleukin-1 receptor; Interleukin-1β; P2Y1 receptor; Thermal hypersensitivity