Annexin A1 exerts analgesic effect in a mouse model of medication overuse headache

Zihua Gong; Chunxiao Yang; Wei Dai; Shuai Miao; Yingyuan Liu; Zhiyang Jiao; Bozhi Li; Wei Xie; Wei Zhao; Xun Han; Shengyuan Yu; Zhao Dong

doi:10.1016/j.isci.2023.108153

Annexin A1 exerts analgesic effect in a mouse model of medication overuse headache

iScience. 2023 Oct 6;26(11):108153. doi: 10.1016/j.isci.2023.108153. eCollection 2023 Nov 17.

Authors

Zihua Gong^{1

2

3}, Chunxiao Yang^{1

4}, Wei Dai¹, Shuai Miao¹, Yingyuan Liu^{1

2}, Zhiyang Jiao⁵, Bozhi Li¹, Wei Xie^{1

2}, Wei Zhao^{1

2}, Xun Han¹, Shengyuan Yu^{1

2}, Zhao Dong^{1

2}

Affiliations

¹ Department of Neurology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China.
² Medical School of Chinese PLA, Beijing 100853, China.
³ Department of Medical Oncology, Bethune International peace Hospital, Shijiazhuang, Hebei 050082, China.
⁴ School of Medicine, Nankai University, Tianjin 300071, China.
⁵ Department of Outpatient, Shijiazhuang Fourth Retired Cadre Sanatorium of Hebei province Military Region, Shijiazhuang, Hebei 050082, China.

Abstract

Medication overuse headache (MOH) is a serious global condition. The interaction between headache attacks and medication overuse complicates the understanding of its pathophysiology. In this study, we developed a preclinical MOH model that incorporates these two key factors by overusing rizatriptan benzoate (RIZ, 4 mg/kg, i.g.) in a glyceryl trinitrate (GTN, 10 mg/kg, i.p.) induced chronic migraine mouse model. We observed that RIZ overuse aggravated GTN-induced cutaneous allodynia and caused a prolonged state of latent sensitization. We also detected a significant upregulation of Annexin-A1 (ANXA1), a protein mainly expressed in the microglia of the spinal trigeminal nucleus caudalis (SPVC), in GTN+RIZ mice. Intracerebroventricular injection of ANXA1-derived peptide Ac2-26 trifluoroacetic acid (TFA) (5 μg/mouse) inhibited bright light stress (BLS) induced acute allodynia via the formyl peptide receptor (FPR) in GTN+RIZ mice. These results suggest that ANXA1 may have an analgesic effect in triptan-associated MOH and could potentially serve as a therapeutic target.

Keywords: Biological sciences; Natural sciences; Pharmacologic activity in systems toxicology; Pharmacology; Physiology; Toxicology.