2. Academic Validation
  3. Compromised PGF2α signaling in the paraventricular hypothalamic nucleus contributes to the central sensitization of the nitroglycerin-induced chronic migraine in male mice

Compromised PGF2α signaling in the paraventricular hypothalamic nucleus contributes to the central sensitization of the nitroglycerin-induced chronic migraine in male mice

  • J Headache Pain. 2025 Aug 6;26(1):179. doi: 10.1186/s10194-025-02124-x.
Xianrong Hu # 1,  Lunquan Wu # 2,  Li Wang 1,  Congxue Peng 1,  Yunyun Tian 3,  Qian Zhu 3,  Hongwei Zhu 4,  Liang Nie 2,  Li Yin 5,  Yuehui Zhang 6,  Jiang Bian 7 8
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Panzhihua Central Hospital, Panzhihua, 617000, China.
  • 2 Department of Anesthesiology, Fushun People's Hospital, Zigong, 643200, China.
  • 3 Clinical Research Center, Panzhihua Central Hospital, Panzhihua, 617000, China.
  • 4 Department of Dermatology, Panzhihua Central Hospital, Panzhihua, 617000, China.
  • 5 Clinical Research Center, Panzhihua Central Hospital, Panzhihua, 617000, China. 425281415@qq.com.
  • 6 Department of Neurology, Panzhihua Central Hospital, Panzhihua, 617000, China. zyh18096306699@163.com.
  • 7 Department of Anesthesiology, Panzhihua Central Hospital, Panzhihua, 617000, China. 1105593984@qq.com.
  • 8 Neuropsychiatry Research Institute, School of Basic Medicine, Qingdao University, Qingdao, 266000, China. 1105593984@qq.com.
  • # Contributed equally.
PMID: 40770605 DOI: 10.1186/s10194-025-02124-x
Abstract

Impaired descending inhibitory controls are now understood to exacerbate central sensitization of chronic migraine, yet the underlying neural and molecular mechanisms remain largely elusive. Herein, a paraventricular hypothalamic nucleus (PVN) oxytocin (OXT) → trigeminal nucleus caudalis (TNC) GABA neural circuit was identified through the application of a rigorous anterograde tracing strategy and RNAscope in situ hybridization techniques, involved in regulating trigeminal nociceptive transmission. In both episodic and chronic migraine mouse models induced by nitroglycerin (NTG) injections, increased activity of the PVN OXT → TNC GABA circuit was observed. However, the activity of PVN OXT neurons decreased in chronic migraine mice when compared to episodic migraine mice. Chemogenetic activation of PVN OXT neurons alleviated migraine hyperalgesia and enhanced the release of OXT and GABA in TNC in chronic migraine mice, while these beneficial effects were abrogated by the intra-TNC administration of OXT receptor antagonist. Interestingly, the expression of prostaglandin F2α receptor (FP) in PVN OXT neurons decreased with the chronification of migraine despite upregulation of PVN prostaglandin F2α (PGF2α) levels. Targeting FP overexpression in PVN OXT neurons restored neuronal activity and ameliorated chronic migraine hyperalgesia. Overall, our study reveals a novel neural and molecular mechanism for descending modulation of trigeminal central sensitization, thereby providing a basis for treating chronic migraine.

Keywords

Central sensitization; Chronic migraine; Descending pain modulation; PGF2α signaling.

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