A machine learning-driven transcriptomic study reveals the key role of Romo1 in reversing central sensitization through stellate ganglion block in migraine: An interventional study based on a recurrent migraine rat model.

Abstract

OBJECTIVES/BACKGROUND: This study utilized a nitroglycerin (NTG)-induced chronic migraine rat model to explore the therapeutic effects and underlying mechanisms of stellate ganglion block (SGB), aiming to clarify the potential pathogenesis of migraine. Central sensitization is key to chronic migraine development. SGB effectively treats chronic pain by reducing sympathetic tone and inhibiting central sensitization. Although SGB is a promising treatment for migraine based on several observational studies, its mechanisms of action remain partially understood. METHODS: Migraine was experimentally induced in rats by administering repeated injections of NTG. Ultrasound-guided SGB was used as the intervention. Hyperalgesia was evaluated through measurements of paw mechanical hyperalgesia, periorbital mechanical threshold, and paw withdrawal latency. The impact of SGB on migraine was assessed by measuring c-fos and calcitonin gene-related peptide (CGRP) levels in the trigeminal nucleus caudalis using Western blotting and immunohistochemistry. Differentially expressed downstream genes were identified through bulk transcriptome sequencing, potential biological mechanisms were explored using gene ontology enrichment analysis, and phenotype characteristic genes were identified through various machine learning algorithms. The expression of key genes was validated using quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry. RESULTS: Repeated NTG treatment increased c-fos and CGRP expression, along with chronic mechanical and thermal hypersensitivity. SGB treatment alleviated hyperalgesic symptoms and decreased CGRP and c-fos levels in the trigeminal nucleus caudalis. Machine learning analysis revealed a significant increase in Romo1 (reactive oxygen species modulator 1) expression in the migraine model, which notably decreased after SGB treatment. Quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry confirmed Romo1's significant role in migraine pathophysiology. CONCLUSION: SGB mitigates central sensitization and reduces migrainelike symptoms in a rat model of migraine induced by repeated NTG exposure. Our results suggest that Romo1 is associated with the effects of SGB, and based on our statistical analysis, is an interesting target for future studies.