Involvement of peripheral P2Y1 receptors and potential interaction with IL-1 receptors in IL-1β-induced thermal hypersensitivity in rats

Soon Gu Kwon, Dae Hyun Roh, Seo Yeon Yoon, Sheu Ran Choi, Hoon Seong Choi, Ji Young Moon, Suk Yun Kang, Alvin J. Beitz, Jang Hern Lee

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)165-172
Number of pages8
JournalBrain Research Bulletin
Volume130
DOIs
StatePublished - Apr 1 2017

Keywords

  • Inflammation
  • Interleukin-1 receptor
  • Interleukin-1β
  • P2Y1 receptor
  • Thermal hypersensitivity

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