TY - JOUR
T1 - Involvement of peripheral P2Y1 receptors and potential interaction with IL-1 receptors in IL-1β-induced thermal hypersensitivity in rats
AU - Kwon, Soon Gu
AU - Roh, Dae Hyun
AU - Yoon, Seo Yeon
AU - Choi, Sheu Ran
AU - Choi, Hoon Seong
AU - Moon, Ji Young
AU - Kang, Suk Yun
AU - Beitz, Alvin J.
AU - Lee, Jang Hern
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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 100 ng), an endogenous IL-1R antagonist, prevented the IL-1β induced mechanical and thermal hypersensitivity. Pre-treatment with MRS2500 (i.pl, 1 and 3 nmol), 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, 0.1 nmol, sub-effective dose) together with IL-1ra (10 nmol, 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 (3 nmol, sub-effective dose) and IL-1ra (30 ng, 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.
AB - 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 100 ng), an endogenous IL-1R antagonist, prevented the IL-1β induced mechanical and thermal hypersensitivity. Pre-treatment with MRS2500 (i.pl, 1 and 3 nmol), 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, 0.1 nmol, sub-effective dose) together with IL-1ra (10 nmol, 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 (3 nmol, sub-effective dose) and IL-1ra (30 ng, 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.
KW - Inflammation
KW - Interleukin-1 receptor
KW - Interleukin-1β
KW - P2Y1 receptor
KW - Thermal hypersensitivity
UR - http://www.scopus.com/inward/record.url?scp=85012084027&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85012084027&partnerID=8YFLogxK
U2 - 10.1016/j.brainresbull.2017.01.019
DO - 10.1016/j.brainresbull.2017.01.019
M3 - Article
C2 - 28153540
AN - SCOPUS:85012084027
SN - 0361-9230
VL - 130
SP - 165
EP - 172
JO - Brain Research Bulletin
JF - Brain Research Bulletin
ER -