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Volume 26
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10.3390/ijms262411983
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

LPS-Induced Neuroinflammation Increases Serotonin-Evoked Activity of Trigeminal Afferents and Aggravates Mechanical Allodynia and Photophobic Behavior in Rat Migraine Model

by
Svetlana Svitko
1,
Elisaveta Ermakova
1,
Karina Gilizhdinova
1,
Ksenia Bogatova
1,
Nazgul Gaifutdinova
1,
Dinara Nurmieva
1,
Egor Nevsky
1,
Anton Ananev
1,
Olga Yakovleva
1,
Albert Sufianov
2,3,
Galina Z. Sufianova
4,
Artyom Baev
5,
Kseniia Shaidullova
1,
Albert Rizvanov
6,7,
Aliya Yakubova
7,8,*,† and
Guzel Sitdikova
1,*,†
1
Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia
2
Petrovsky National Research Center of Surgery, 119435 Moscow, Russia
3
The Research and Educational Institute of Neurosurgery, Peoples’ Friendship University of Russia (RUDN), 117198 Moscow, Russia
4
Department of Pharmacology, Tyumen State Medical University, 625023 Tyumen, Russia
5
Laboratory of Experimental Biophysics, Centre for Advanced Technologies, Tashkent 100174, Uzbekistan
6
Division of Medical and Biological Sciences, Tatarstan Academy of Sciences, 420111 Kazan, Russia
7
Department of Gene and Cell Technology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420021 Kazan, Russia
8
Department of Pathophysiology, Kyrgyz State Medical Academy, Bishkek 720020, Kyrgyzstan
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2025, 26(24), 11983; https://doi.org/10.3390/ijms262411983
Submission received: 5 November 2025 / Revised: 1 December 2025 / Accepted: 3 December 2025 / Published: 12 December 2025
(This article belongs to the Section Molecular Biology)
Versions Notes

Abstract

Migraine is characterized by severe pain and somatic symptoms like allodynia and photophobia, driven by neuroinflammation that sensitizes the trigeminal vascular system (TVS). This study investigated how neuroinflammation induced by systemic lipopolysaccharide (LPS) affects migraine-related nociceptive signaling. Using a chronic migraine model in rats with nitroglycerin (NTG), we compared prenatal and acute postnatal LPS administration. Rats with prenatal LPS exhibited lower mechanical thresholds and enhanced allodynia and photophobia after NTG. Acute LPS also increased allodynia, but not photophobia. Both LPS groups showed increased mast cell degranulation in the dura mater. Plasma CGRP after NTG administration was elevated in the acute LPS group. Electrophysiology revealed enhanced trigeminal afferent responses to serotonin in both acutely and prenatally LPS-treated rats. Calcium imaging demonstrated increased neuronal responses to serotonin and capsaicin, suggesting an upregulation of serotonin and TRPV1 receptors. Our findings show that LPS-induced neuroinflammation, whether prenatal or acute, promotes sensitization of peripheral and central nociceptive pathways, involving serotoninergic mechanisms.
Keywords: neuroinflammation; migraine; sensitization; LPS; trigeminal system; mechanical allodynia; photophobia; mast cell; CGRP neuroinflammation; migraine; sensitization; LPS; trigeminal system; mechanical allodynia; photophobia; mast cell; CGRP

Share and Cite

MDPI and ACS Style

Svitko, S.; Ermakova, E.; Gilizhdinova, K.; Bogatova, K.; Gaifutdinova, N.; Nurmieva, D.; Nevsky, E.; Ananev, A.; Yakovleva, O.; Sufianov, A.; et al. LPS-Induced Neuroinflammation Increases Serotonin-Evoked Activity of Trigeminal Afferents and Aggravates Mechanical Allodynia and Photophobic Behavior in Rat Migraine Model. Int. J. Mol. Sci. 2025, 26, 11983. https://doi.org/10.3390/ijms262411983

AMA Style

Svitko S, Ermakova E, Gilizhdinova K, Bogatova K, Gaifutdinova N, Nurmieva D, Nevsky E, Ananev A, Yakovleva O, Sufianov A, et al. LPS-Induced Neuroinflammation Increases Serotonin-Evoked Activity of Trigeminal Afferents and Aggravates Mechanical Allodynia and Photophobic Behavior in Rat Migraine Model. International Journal of Molecular Sciences. 2025; 26(24):11983. https://doi.org/10.3390/ijms262411983

Chicago/Turabian Style

Svitko, Svetlana, Elisaveta Ermakova, Karina Gilizhdinova, Ksenia Bogatova, Nazgul Gaifutdinova, Dinara Nurmieva, Egor Nevsky, Anton Ananev, Olga Yakovleva, Albert Sufianov, and et al. 2025. "LPS-Induced Neuroinflammation Increases Serotonin-Evoked Activity of Trigeminal Afferents and Aggravates Mechanical Allodynia and Photophobic Behavior in Rat Migraine Model" International Journal of Molecular Sciences 26, no. 24: 11983. https://doi.org/10.3390/ijms262411983

APA Style

Svitko, S., Ermakova, E., Gilizhdinova, K., Bogatova, K., Gaifutdinova, N., Nurmieva, D., Nevsky, E., Ananev, A., Yakovleva, O., Sufianov, A., Sufianova, G. Z., Baev, A., Shaidullova, K., Rizvanov, A., Yakubova, A., & Sitdikova, G. (2025). LPS-Induced Neuroinflammation Increases Serotonin-Evoked Activity of Trigeminal Afferents and Aggravates Mechanical Allodynia and Photophobic Behavior in Rat Migraine Model. International Journal of Molecular Sciences, 26(24), 11983. https://doi.org/10.3390/ijms262411983

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