Chronic Migraine: Pathophysiology, Clinical Presentation, Current Management, and Emerging Translational Therapies

Abstract

Chronic migraine is a debilitating neurological condition that affects millions worldwide. People with this disorder experience headaches on at least 15 days each month for more than three months, with at least eight of those days having migraine features. This condition doesn't develop from a single cause but rather emerges from a complex interplay of genetic predisposition, nervous system dysfunction, inflammation, and environmental triggers.

Mental health conditions, sleep problems, obesity, medication overuse, and life stress can all make chronic migraine worse and harder to treat. Doctors diagnose chronic migraine through careful clinical evaluation using the International Classification of Headache Disorders criteria, and only order additional tests when they spot unusual features or "red flags."

Treatment today combines medications for acute attacks, preventive therapies, lifestyle changes, and sometimes neuromodulation techniques. The development of drugs targeting CGRP (calcitonin gene-related peptide) has expanded treatment options significantly. However, responses vary widely among patients, and access, cost, long-term safety questions, and practical implementation remain significant hurdles.

Exciting new approaches like nanotechnology-based drug delivery and CRISPR gene editing show scientific promise, but they're still largely in early research stages for migraine. For these technologies to benefit patients, they'll need to demonstrate they can reach the right tissues safely, be manufactured reliably, and meet regulatory standards. This review examines what we currently understand about chronic migraine, acknowledges the gaps in our knowledge, and discusses the obstacles that prevent promising discoveries from reaching patients (Ferrari et al., 2022; Puledda et al., 2023).