Chronic Migraine – Modern Scientific Answers to the Most Important Patient Questions

Introduction This article is based on the peer-reviewed scientific review “Chronic Migraine Pathophysiology and Treatment: A Review of Current Perspectives,” published in 2021 in Frontiers in Pain Research. The authors of the publication are Tiffany J. Mungoven, Luke A. Henderson, and Noemi Meylakh – researchers from the Department of Anatomy and Histology at the Brain and Mind Centre, University of Sydney, Australia. The review provides an in-depth overview of the current understanding of chronic migraine – its clinical features, pathophysiology, chronification factors, structural and functional brain changes, as well as current and emerging treatment options.

The following questions and answers summarize key findings from the article, aimed at patients seeking scientifically grounded yet accessible information about chronic migraine.

Expert Insights

1. What is chronic migraine, and how serious is this condition? “Chronic migraine is a disabling neurological disorder that imposes a significant burden on individual health and socio-economic outcomes. Chronic migraine is defined as having headaches on at least 15 days per month, with at least 8 of those days meeting the criteria for migraine headache. It often develops from episodic migraine due to increased attack frequency and/or the presence of various risk factors.”

Context: This definition highlights that chronic migraine is much more than “frequent headaches”—it has specific diagnostic criteria and a profound impact on quality of life and a person’s ability to function socially and economically.

2. What are the main mechanisms behind the development and persistence of chronic migraine? “Chronic migraine is likely a distinct clinical entity with its own unique features and pathophysiology, differentiating it from episodic migraine… At its core are functional and structural changes in the brain, central sensitization, and neuroinflammation.”

Context: Unlike milder forms, chronic migraine is associated with structural and functional brain changes, including processes like central sensitization (increased sensitivity of the nervous system to pain) and inflammation in nerve tissues.

3. Why is treatment often unsuccessful, and what are the new approaches? “Current treatment options for chronic migraine include modification of risk factors, acute and preventive therapy, established medications such as onabotulinumtoxinA, topiramate, and newly developed monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor… Unfortunately, treatment is often ineffective in terminating attacks or reducing their intensity and frequency, and poor adherence to preventive medications remains a major challenge. New methods such as neuromodulation offer promising alternatives that require further research.”

Context: The main issue is that most treatments only work partially and are often not used long enough or correctly. New drug classes and device-based therapies offer hope, but more research and individualized care are needed.

4. What are the most common risk factors for developing chronic migraine? “Risk factors for progression include high initial attack frequency in episodic migraine, overuse of acute medications, obesity, stressful life events, female gender, and lower socio-economic status… Comorbid psychiatric conditions such as anxiety and depression are also more common in patients with chronic migraine and worsen prognosis.”

Context: These factors are crucial for prevention and effective treatment. Especially important is timely behavioral correction (reducing medication use, managing stress, maintaining a healthy weight), as well as identifying and treating mental health disorders.

5. What are the experts’ recommendations and future perspectives? “While topiramate, onabotulinumtoxinA, and the newer anti-CGRP monoclonal antibodies are currently the only proven options for preventing chronic migraine, neuromodulation is creating new and promising treatment opportunities. Further studies are needed to determine whether effective therapies can prevent or reverse the structural and functional brain changes observed in chronic migraine. The development of new models and advances in neuroimaging techniques will support the discovery of individualized treatment strategies.”

Context: Leading researchers believe the future lies in personalized therapies based on a deeper understanding of brain changes in chronic migraine. This means more research, more individualized approaches, and likely better treatment outcomes.

Q&A Section

1. How can I tell if I have chronic migraine and not just frequent headaches? Answer: To be diagnosed with chronic migraine, you must have headaches on at least 15 days per month, with at least 8 of those days meeting the criteria for migraine (i.e., throbbing, severe pain, often one-sided, accompanied by symptoms like nausea, sensitivity to light and sound). This must continue for at least three consecutive months. Migraines often occur in different phases – a “prodrome” phase (mood changes, fatigue, neck stiffness 24–48 hours before the attack), the headache itself, and a “postdrome” phase with symptoms like exhaustion and difficulty concentrating.

2. What is “central sensitization,” and why is it important in chronic migraine? Answer: Central sensitization means your nervous system becomes overly sensitive to pain signals. In chronic migraine, the brain – particularly areas like the trigeminal system – starts to overreact to otherwise mild or normal stimuli. This results in a lower pain threshold, more frequent and intense attacks, and pain from normally non-painful stimuli (known as allodynia – for example, pain when brushing your hair or touching your face). This hypersensitivity is a key reason why migraines become chronic and worsen over time.

3. What is “medication overuse headache,” and why should I be cautious with medications? Answer: Medication overuse headache (MOH) is a form of chronic migraine that develops when painkillers are used too frequently—such as triptans, opioids, or combination analgesics. Risks increase if you have a family history or a tendency toward dependency. In many patients, stopping or limiting these medications leads to improvement and can even reverse some brain changes. That’s why it’s important not to use painkillers more than 2 days a week and to consult a neurologist about alternative preventive strategies.

4. What brain changes are seen in chronic migraine? Answer: Chronic migraine is associated with both functional and structural brain changes. Studies show increased gray matter volume in areas like the amygdala, putamen, and periaqueductal gray (PAG), and decreased volume in regions such as the anterior cingulate cortex, temporal and occipital lobes, brainstem, and cerebellum. Functional MRI studies also reveal disrupted connectivity between different brain networks, increased activity in pain-processing systems, and higher excitability in the visual cortex—even between attacks. These changes are linked to more frequent and intense episodes and greater disability in chronic migraine.

5. Are there any alternative (non-pharmacological) treatments I can discuss with my doctor if medications aren’t helping? Answer: Yes, there are new non-pharmacological approaches being actively studied for chronic migraine. One of the most promising is neuromodulation, which involves using different devices to stimulate specific nerves or brain regions. Non-invasive techniques include transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and non-invasive vagus nerve stimulation (nVNS), as well as invasive methods using implanted devices. Early results are encouraging, but more research is needed to assess long-term effectiveness and safety. Patients who don’t respond to standard medications can talk to their neurologist about these therapies or participation in clinical trials.

Conclusion Chronic migraine is a complex and highly disabling condition, where patients face not only frequent and painful attacks but also numerous risk factors, comorbid conditions, and treatment challenges. The scientific review by Mungoven, Henderson, and Meylakh emphasizes that successful management of the disorder requires an integrated approach—from early diagnosis and addressing medication overuse, to tackling mental health and social factors, and applying personalized treatment strategies that include both medications and non-drug therapies. Advances in neuroscience and modern medicine are gradually leading to more effective, individualized treatment options—offering hope to patients with chronic migraine and their loved ones.

All information in this section is based entirely on the scientific publication by Mungoven, Henderson & Meylakh (2021), providing the most up-to-date and evidence-based data on this often misunderstood condition.

Source: Mungoven TJ, Henderson LA, Meylakh N. Chronic Migraine Pathophysiology and Treatment: A Review of Current Perspectives. Frontiers in Pain Research, 2021;2:705276.