Changes in P2X4 receptor expression following AbobotulinumtoxinA treatment in patients with chronic migraine: A case...

Background: Chronic migraine (CM) is a debilitating neurological disorder often complicated by medication overuse (MO). While abobotulinumtoxinA (ABO-BoNT-A) is a well-established preventive treatment for CM, its molecular mechanisms are not fully understood. Emerging evidence suggests that neurotrophic tyrosine receptor kinase 2 (NTRK2), SRC kinase signaling inhibitor 1 (SRCIN1), and P2X4 purinergic receptor (P2X4R) are involved in migraine chronification and botulinum neurotoxin A (BoNT-A) function, but their roles in humans remain underexplored. This case series investigated changes in NTRK2, SRCIN1, and P2X4R gene expression in peripheral blood pre- and post-BoNT-A treatment and assessed associated clinical outcomes in patients. Methods: The messenger ribonucleic acid (mRNA) levels of NTRK2, SRCIN1, and P2X4R genes were analyzed in a sample of eight patients with CM and MO following BoNT-A treatment using quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, migraine characteristics were assessed using Migraine Disability Assessment Scale (MIDAS), Headache Impact Test-6 (HIT-6), and Patient Health Questionnaire-9 (PHQ-9). Results: The intervention resulted in early measurable improvements in migraine symptoms and disability. Post-treatment, P2X4R expression significantly increased (P < 0.05), while NTRK2 and SRCIN1 showed no significant changes. Conclusion: Findings indicate that P2X4R upregulation may be linked to the therapeutic effects of BoNT-A, while NTRK2 and SRCIN1 appear uninvolved. The trend in P2X4R expression suggests it may serve as a predictive biomarker and therapeutic target, but further validation in larger cohorts is necessary.