CGRP–uric acid axis in migraine: A redox–inflammatory framework linking neurovascular signaling and metabolic regulation
Year: 2026
Type: article
Abstract: Migraine arises from a complex interplay between neuronal, vascular, inflammatory, and metabolic processes. Calcitonin gene-related peptide (CGRP) is widely recognized as a major mediator within the trigeminovascular system, while accumulating evidence suggests that uric acid (UA) may influence redox balance and inflammatory signaling. However, these mechanisms are often discussed separately. This review summarizes current evidence regarding CGRP signaling, oxidative stress, and UA metabolism, and proposes a hypothesis-generating CGRP-UA redox-inflammatory framework in migraine. Within this conceptual model, CGRP-associated oxidative stress may contribute to neuronal sensitization and neurogenic inflammation, whereas oxidative stress may link neuropeptide activity with downstream immune and metabolic responses. UA exhibits context-dependent effects, functioning as an extracellular antioxidant through radical scavenging, lipid peroxidation chain-breaking, and metal chelation, while potentially contributing to oxidative stress and inflammasome activation following intracellular accumulation. These pathways appear to converge on shared mediators, including reactive oxygen species, nuclear factor kappa B, and the NLRP3 inflammasome, suggesting possible interactions within the trigeminovascular system. However, much of the current mechanistic evidence is indirect and derived from non-migraine experimental systems. Therefore, the proposed CGRP-UA framework should be regarded as conceptual and hypothesis-generating rather than mechanistically established. This integrative perspective may nevertheless help guide future studies investigating biomarker interpretation, redox biology, and therapeutic targeting in migraine.
Source: Biomedicine & Pharmacotherapy
Authors: Chien-Lin Lu, Yu-Chen Cheng, Kuo-Cheng Lu
Institutions: Fu Jen Catholic University, Taipei Tzu Chi Hospital
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,610
OpenAlex ID: W7165775088