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

Zhale  Salami; Saeed  Irian; Mansoureh  Togha; Elham  Jafari; Delara  Hazegh-Fetratjoo

doi:10.18502/cjn.v24i3.21595

Zhale Salami Department of Cellular and Molecular Biology, School of Biological Sciences, Kharazmi University, Tehran, Iran
Saeed Irian Department of Cellular and Molecular Biology, School of Biological Sciences, Kharazmi University, Tehran, Iran
Mansoureh Togha Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
Elham Jafari Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
Delara Hazegh-Fetratjoo School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/cjn.v24i3.21595

Keywords: Chronic Migraine; Medication Overuse Headache; AbobotulinumtoxinA; Gene Expression; NTRK2; Case Series

Abstract

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.