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.
Zihua Gong  1  2  3 ,  Chunxiao Yang  1  4 ,  Wei Dai  1 ,  Shuai Miao  1 ,  Yingyuan Liu  1  2 ,  Zhiyang Jiao  5 ,  Bozhi Li  1 ,  Wei Xie  1  2 ,  Wei Zhao  1  2 ,  Xun Han  1 ,  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.
PMID: 37867938 DOI: 10.1016/j.isci.2023.108153
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.
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