2. Academic Validation
  3. Activation of G-protein-coupled receptor 183 initiates inflammatory pain via macrophage CCL22 secretion

Activation of G-protein-coupled receptor 183 initiates inflammatory pain via macrophage CCL22 secretion

  • Eur J Pharmacol. 2023 Jun 21;954:175872. doi: 10.1016/j.ejphar.2023.175872.
Zhenhua Qi 1,  Weiqiang Zhong 1,  Boyu Jiao 2,  Kang Chen 1,  Xiaohua Yang 1,  Linjie Wang 3,  Weian Zeng 1,  Junting Huang 4,  Jingdun Xie 5
Affiliations

Affiliations

  • 1 Department of Anesthesiology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
  • 2 Department of Acupuncture, The First Affiliated Hospital, SunYat-sen University, Guangzhou, Guangdong, 510080, China.
  • 3 Department of Human Anatomy and Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
  • 4 Department of Human Anatomy and Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China. Electronic address: huangjt56@mail.sysu.edu.cn.
  • 5 Department of Anesthesiology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. Electronic address: xiejd6@mail.sysu.edu.cn.
PMID: 37353188 DOI: 10.1016/j.ejphar.2023.175872
Abstract

Chronic pain is a major public health problem with limited effective therapeutic options. G-protein-coupled receptors play a significant role in pain modulation; however, whether and how G-protein-coupled receptor 183 participates in pain regulation remain unclear. In the present study, we found that G-protein-coupled receptor 183 expression was specifically upregulated in the hind paws of mice in various inflammatory pain models. Activation of G-protein-coupled receptor 183 induced acute pain, whereas inhibition or silencing of this receptor alleviated mechanical allodynia and thermal hyperalgesia in complete Freund's Adjuvant (CFA) model. Mechanistically, activating G-protein-coupled receptor 183 triggers pain responses via the upregulation of C-C motif chemokine 22(CCL22) in macrophages while blocking the CCL22 receptor C-C motif Chemokine Receptor 4 (CCR4) attenuates pain hypersensitivity. Taken together, our findings indicate that the G-protein-coupled receptor 183-CCL22 axis has a critical role in the development and maintenance of inflammatory pain.

Keywords

CCL22; G-protein-coupled receptor 183; Inflammatory pain; Macrophage.

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