Chemokine receptor CXCR2 in primary sensory neurons of trigeminal ganglion mediates orofacial itch

Dong-Jin Li; Zhen-Juan Zhong; Xiao-Liang Wang; Na Wei; Si-Jia Zhao; Ting-Ting Shan; Ya-Ping Liu; Yao-Qing Yu

doi:10.3389/fnmol.2023.1279237

Chemokine receptor CXCR2 in primary sensory neurons of trigeminal ganglion mediates orofacial itch

Front Mol Neurosci. 2023 Oct 26:16:1279237. doi: 10.3389/fnmol.2023.1279237. eCollection 2023.

Authors

Dong-Jin Li^#^{1

2

3}, Zhen-Juan Zhong^#^{2

3}, Xiao-Liang Wang^#^{2

3}, Na Wei^{2

3}, Si-Jia Zhao^{2

3}, Ting-Ting Shan^{2

3}, Ya-Ping Liu^{2

3}, Yao-Qing Yu^{1

2

3}

Affiliations

¹ College of Life Sciences, Northwest University, Xi'an, China.
² Institute for Biomedical Sciences of Pain, Tangdu Hospital, Air Force Medical University, Xi'an, China.
³ Key Laboratory of Brain Stress and Behavior, People's Liberation Army, Xi'an, China.

^# Contributed equally.

Abstract

The CXCR2 chemokine receptor is known to have a significant impact on the initiation and control of inflammatory processes. However, its specific involvement in the sensation of itch is not yet fully understood. In this study, we aimed to elucidate the function of CXCR2 in the trigeminal ganglion (TG) by utilizing orofacial itch models induced by incision, chloroquine (CQ), and histamine. Our results revealed a significant up-regulation of CXCR2 mRNA and protein expressions in the primary sensory neurons of TG in response to itch stimuli. The CXCR2 inhibitor SB225002 resulted in notable decrease in CXCR2 protein expression and reduction in scratch behaviors. Distal infraorbital nerve (DION) microinjection of a specific shRNA virus inhibited CXCR2 expression in TG neurons and reversed itch behaviors. Additionally, the administration of the PI3K inhibitor LY294002 resulted in a decrease in the expressions of p-Akt, Akt, and CXCR2 in TG neurons, thereby mitigating pruritic behaviors. Collectively, we report that CXCR2 in the primary sensory neurons of trigeminal ganglion contributes to orofacial itch through the PI3K/Akt signaling pathway. These observations highlight the potential of molecules involved in the regulation of CXCR2 as viable therapeutic targets for the treatment of itch.

Keywords: CXCR2; incision; orofacial itch; trigeminal ganglion; virus.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study was supported by National Natural Science Foundation of China (grant 31871067) and AFMU (grant 2021HKYX29) (Y-QY).