Headache and Migraine — A Bell That Rings Easily, a Threshold That Falls as Attacks Grow Frequent

The Painkiller in the Drawer

The desk drawer of a 42-year-old office worker always holds painkillers. When afternoon meetings run long, his head tightens, and a couple of times a month, one side of his head throbs so badly he has to turn off the lights and lie down. Lately, the days he takes medicine have increased compared to before. A colleague says, "Everyone gets headaches," and the internet lines up frightening disease names.

Headaches are common to that degree. In an analysis gathering 357 surveys, people suffering from headache disorders made up about 52% of the global population, and if you slice up a single day, about 15.8% of people had a headache that day. Most of the surveys came from high-income countries (PMID 35410119). In the United States, nine out of ten people experience a headache at least once in their lives (PMID 33974014).

Common does not mean light. Headaches are mostly diseases in themselves, and rarely, signals of other illnesses. This article looks in turn at how headaches are divided, how the most studied headache happens inside the head, and what medications do and when they invite headaches instead.

Two Paths of Headaches

Headaches are first divided into two types. Primary headaches are headaches where there is no other illness, and the headache itself is the disease. Secondary headaches are headaches that occur because of another illness, as a symptom of that illness. Vascular disease, tumors, infections, and changes in pressure inside the head are cited as causes of secondary headaches (PMID 33974014).

Primary headaches are divided into four groups (PMID 33974014). The names and diagnostic criteria of headaches follow the International Classification of Headache Disorders (ICHD), and they are currently diagnosed using its third edition (PMID 36732518). The best-known primary headache is migraine. A migraine is a primary headache that frequently involves recurring throbbing attacks on one side of the head, accompanied by nausea or sensitivity to light and sound. An attack in the context of headaches refers to a single episode from the time a headache arrives until it subsides.

The vast majority of headaches are primary headaches (PMID 38419454). Although people suffering from secondary headaches make up a small proportion, failing to tell them apart from primary headaches greatly worsens the risk of illness and death (PMID 37456555). Therefore, the first question in examining a headache is, "Is this headache primary or secondary?" (PMID 33974014).

This distinction is made mainly through a conversation. Headache care relies heavily on asking when and how it started, how often it occurs, where it hurts, and what the pain feels like. Listening to the story in a structured way allows for an accurate diagnosis and often avoids the need for unnecessary tests (PMID 38568485).

Most headaches are primary headaches where the headache itself is the disease, and their names are sorted out mainly through the stories heard in the examination room.

Headaches to Check Promptly

Among rare secondary headaches, some are a race against time. A thunderclap headache is a very severe headache that begins suddenly, as if bursting, and peaks within one minute. It has multiple causes, and the most concerning among them is subarachnoid hemorrhage (PMID 30334463). Subarachnoid hemorrhage is bleeding where blood leaks into the space beneath the membrane wrapping the brain. This bleeding is the most common secondary cause of a thunderclap headache (PMID 33661161), and because the risk of illness and death is high, a thunderclap headache requires a prompt search for its cause (PMID 30334463).

Signals that raise suspicion of a secondary headache go beyond the thunderclap headache. Sudden onset, very intense pain, a change in the pattern of a pre-existing headache, neurological symptoms or seizures such as weakness on one side of the body, systemic symptoms like fever, and a headache that starts during physical exertion are those signals (PMID 37456555). When the membrane wrapping the brain becomes inflamed, adults and older children may experience a stiff neck, fever, headache, and altered consciousness together, and if bacteria are the cause, guidelines recommend starting treatment within one hour of arriving at the hospital (PMID 41839077). Having cancer, an immune-compromised state, or a headache that occurs when changing positions are also counted as signals to examine promptly (PMID 33974014). A headache that has newly developed and continues every day is as well (PMID 15617293). Older individuals including those 50 and older, pregnant women, and people with compromised immunity face a higher risk of secondary headaches, leading doctors to set different criteria for initiating tests (PMID 33974014, PMID 33896523).

A secondary headache can strike even someone who already has a headache (PMID 37456555). Even if it is a familiar, recurring headache, if its pattern has changed, that change is a signal.

Recognizing the signals is something anyone can do, but sorting out the cause requires a medical exam and tests. One review article recommends that every patient with a thunderclap headache undergo a brain CT (computed tomography) scan (PMID 30334463). The subsequent test is chosen by the medical team based on when the CT was taken after the headache began and the degree of suspicion (PMID 33661161). In the absence of red flags, a primary headache is likely (PMID 38419454).

Secondary headaches are rare, but a headache that begins suddenly like an explosion, or one accompanied by neurological symptoms or fever, is checked promptly through a medical exam and tests.

The Disease Called Migraine

Migraine pain is characterized by throbbing strongly on one side (PMID 30982963), and sensitivity to light and sound, nausea and vomiting, and pain that worsens with movement are the most common symptoms (PMID 38043959). An attack goes through multiple stages: the premonitory phase before the headache, the headache phase, and the postdromal phase after the headache clears (PMID 38043959).

In an analysis pooling 357 surveys, migraines were present in 14.0% of the global population (PMID 35410119). Among primary headaches, migraine causes the greatest disability, and it is the second leading cause of years lived with disability worldwide (PMID 33974014). It is two to three times more common in women, and women report attacks that are longer and more severe (PMID 40265504).

Migraine is a chronic disease that disrupts daily life with recurring attacks (PMID 35027572). Even though it is a common and highly disabling neurological disease, it is frequently unrecognized and untreated (PMID 30982963).

Between 15% and roughly a third of people with migraines experience an aura (PMID 34384631). An aura is a phenomenon where neurological symptoms, such as flashes of light before the eyes, appear gradually around the time of a migraine attack and then completely disappear. Visual auras account for over 90%, and they can also affect sensation or speech. Each individual symptom develops gradually, lasting no longer than an hour, and usually precedes the headache (PMID 34384631).

There are also emergencies that resemble an aura. If an aura is absent and only other neurological symptoms occur, if multiple symptoms occur all at once, or if the symptoms match the area supplied by a single blood vessel in the brain, clinicians urgently check whether blood flow to the brain was briefly blocked. Symptoms lasting over an hour, a first-ever aura appearing at an older age, and a sudden, sharp increase in the frequency of auras are also targets for evaluation. When experiencing an aura for the first time, it is sometimes difficult even for the person themselves to tell whether it came on gradually or suddenly (PMID 34384631).

Migraines are a neurological disease that disrupts daily life, and a portion of those affected experience an aura.

How Migraines Happen in the Head

Migraines were long explained as a disease caused by blood vessels in the head widening. Our current understanding is different. The widening of blood vessels is a secondary phenomenon, and the action of narrowing blood vessels is not what makes migraine medication work (PMID 35027572).

Nerve cells are the basic cells of the brain and nerves that receive electrical signals and pass them on to the next cell. The cerebral cortex is the thin layer covering the outer surface of the brain, a place spread out with zones that divide up movement, speech, and sensation. Aura appears to come from a phenomenon where the electrical state of nerve cells spreads like a wave along this cerebral cortex (PMID 34384631). There is also the possibility that this wave awakens the sensory nerves of the head, kicking off the headache (PMID 35027572).

That sensory nerve is the trigeminal nerve. The trigeminal nerve is a nerve that carries sensations from the face, the front of the head, and the membranes wrapping the brain up to the brain. The cells of this nerve possess both branches stretching out alongside the blood vessels of the membranes wrapping the brain and endings that pass signals on toward the brain (PMID 30982963). In 1979, a hypothesis emerged that this nerve plays a central role in migraines, and 40 years later, there is broad agreement that this nerve and its branches alongside blood vessels play a foundational role in migraines (PMID 31160203).

CGRP is a small protein released by the nerve cells of the trigeminal nerve, which widens blood vessels and participates in processing pain signals. The name is an acronym for calcitonin gene-related peptide. Evidence that CGRP is involved in migraines has also come from humans. During a migraine attack, CGRP is released into the venous blood coming from the head, and injecting CGRP intravenously into someone with migraines produces symptoms similar to a migraine (PMID 28485848). Even during times without an attack, CGRP has been found to be higher in the blood of people with migraines than in healthy people (PMID 38307640).

There is also an explanation that CGRP's job does not end with widening blood vessels. One review article summarizes that CGRP can make the trigeminal nerve sensitive, keep that sensitivity going, and even make the nerve cells receiving signals on the brain side sensitive (PMID 30982963). The evidence obtained from humans has led to drugs that block CGRP, but there is still much to learn about what exact role CGRP plays in headaches and at which site it acts (PMID 28485848).

A brain with migraines can be compared to a bell. Just as the intensity at which it begins to ring differs for each bell, migraines have a threshold where an attack begins, and the explanation is that certain underlying factors and frequent headaches lower that threshold, which is the path to more frequent migraines (PMID 27389092). If the threshold is low, even a light tap makes the bell ring, and once it rings, that resonance spreads through the trigeminal nerve and CGRP into the head. The limits of the metaphor are also clear. A bell is singular, but in migraines, multiple sites of the brain and nerves are intertwined together like a net (PMID 37029836), and what taps the bell has not yet been fully revealed.

The center of a migraine is the trigeminal nerve and the CGRP released by that nerve, while the widening of blood vessels is secondary.

Drugs That Quench Attacks, Drugs That Cut Their Frequency

Headache medications are divided into two main branches (PMID 33767185, PMID 41572863). Acute treatment is therapy used when a headache attack arrives, intended to quiet that attack. Preventive treatment is therapy used steadily even on days without an attack, intended to reduce how often attacks come and how intense they are. When attacks are frequent or severe, preventive treatment is considered (PMID 41572863).

Nonsteroidal anti-inflammatory drugs are a group of anti-inflammatory painkillers widely used to reduce pain, fever, and inflammation. For mild or moderate migraine attacks, common fever reducers and nonsteroidal anti-inflammatory drugs are used first (PMID 40238974). Triptans are a family of acute treatment medications designed specifically to target migraine attacks. They are the drugs used first for moderate-to-severe attacks (PMID 40238974).

A placebo is a fake medicine that looks identical but contains no active medical ingredients. In an analysis gathering 137 randomized trials and 89,445 participants, all 17 oral acute treatment drugs had more people whose pain disappeared two hours later than a placebo did, and the triptans—the group with the best effectiveness—were more effective even than newer drugs. The authors concluded that people with high cardiovascular risk should be evaluated cautiously while considering these drugs as the preferred acute treatment (PMID 39293828).

Still, only 20% to 30% of people have their pain completely disappear within two hours of taking a triptan, and about 25% briefly experience side effects such as a hot flush or a tightening sensation in the upper body. Because this family has the property of narrowing blood vessels, it is avoided by people who have cardiovascular disease or are at high risk for it (PMID 33974014). Newer acute treatments—including oral drugs that block CGRP—are not linked to blood vessel spasms or increased cardiovascular risk, opening another path for adults with migraines who have a high cardiovascular risk of more than 20% (PMID 38568487). However, their effectiveness was smaller than that of the triptans, which work best (PMID 39293828), and data on people who already have or recently experienced vascular disease are still sparse (PMID 40537071).

In its 2025 guidelines, the American College of Physicians (ACP) recommends that doctors add triptans for adults (excluding pregnant women) who have moderate or worse attacks that are not adequately helped by pain relievers alone (PMID 40096690). Because no single drug suits everyone, people sometimes try several different ones before finding the right match (PMID 38568487).

For a long time, preventive treatments borrowed drugs originally made for other conditions (PMID 38466028). These belong to blood pressure medication, epilepsy medication, and antidepressant families (PMID 33974014). Injectable drugs blocking CGRP, used since 2018, are the first drugs built specifically from the start to prevent migraines (PMID 40121062).

The size of the effect is measured in days compared to a placebo. Preventive medications reduce migraine days by 1 to 3 days per month compared to a placebo (PMID 33974014). Among people who had an average of 8 migraine days a month, oral preventive drugs reduced 0.4 to 1.4 days per month compared to a placebo. Injectable drugs blocking CGRP reduced 0.7 to 3.8 days per month depending on the drug in trials examining people with occasional migraines and those with 15 or more days a month together, and they were effective even for people whom existing oral preventives failed to help (PMID 41572863). Because the baseline number of days differed at the start, these figures cannot be directly compared to the preceding numbers.

Safety can be seen in an analysis gathering 74 trials and 32,990 people. Drugs blocking CGRP did not increase the number of people stopping the drug due to side effects compared to a placebo, and the performance combining effectiveness and safety was best among preventive drugs for injectables, with oral drugs blocking CGRP following immediately behind (PMID 37208596). In 2024, the American Headache Society issued a position stating that these drugs should be viewed as preventive treatments that can be chosen from the outset—alongside existing first-choice drugs and without waiting for other drugs to fail (PMID 38466028).

There is also prevention without drugs. In a 2024 review, only two psychological and behavioral treatments were among the drug-free methods with established evidence. Although not quite reaching the level of being established, the evidence for aerobic endurance exercise was among the best for migraine prevention. It noted that drug-free methods should be recommended together even if preventive medications are used (PMID 38885654).

There are also limitations. A 2020 review noted that these drugs relieve symptoms in about half of patients, while the other half do not respond well (PMID 32003253). Although they have been surprisingly safe so far, a few side effects are coming to light (PMID 41296986), and data on people who already have or recently experienced vascular disease are still sparse (PMID 40537071). Long-term safety and value for money also require further study (PMID 40121062). In 2025, the International Headache Society (IHS) suggested that even if migraine days are cut in half, quality of life might not fully return, and proposed targeting the remaining number of days itself. The basis for this is that some individuals can reach a migraine-free state (PMID 39980456).

Drugs blocking CGRP are a new preventive treatment that reduces days per month compared to a placebo, and they do not work for everyone.

Two Other Primary Headaches

Tension-type headache is a primary headache where both sides of the head feel a mild to moderate pressing or tightening pain, which does not get worse with everyday movement. It is the most common neurological disorder in the world (PMID 33767185), and an analysis combining 357 surveys found it in 26.0% of the world's population (PMID 35410119). Diagnosis is made by listening to the story of the headache and ruling out other causes (PMID 33767185). People with this headache tend to have tighter muscles and are more tender when pressed, but whether this is a cause or an effect is not clear (PMID 34599406). For acute treatment, simple painkillers are used first, and if headaches are frequent, preventive treatment is considered (PMID 33767185).

Migraine and tension-type headache share overlapping features. Both often start in the twenties, are triggered by psychological factors like stress, and the trigeminal nerve and its blood vessel branches are involved in the mechanisms of both. There is no test or biomarker to tell the two apart, and both can occur together in the same person (PMID 37474899).

Cluster headache is a rare primary headache where excruciating pain around one eye lasts from 15 minutes to 3 hours, accompanied by tearing or redness in the same eye. The pain strictly stays on one side, and female patients describe individual attacks as more painful than childbirth (PMID 29493566). Periods when attacks cluster and periods of remission alternate, and if the remission period is less than three months, it is classified as chronic (PMID 40437707).

The hypothalamus is a small area deep beneath the brain that receives nerve signals and releases hormones. In cluster headache, this hypothalamus is pointed to as the site that triggers both the pain and symptoms like tearing (PMID 29493566). Breathing oxygen and injectable triptans are most effective for stopping an attack, but the overall evidence for cluster headache treatments is limited (PMID 40437707). One of the injectable drugs blocking CGRP was approved in the United States for the preventive treatment of cluster headache with remission periods of three months or longer, but the same effect was not repeated in chronic cluster headache (PMID 38876749). The effect of this class of drugs in cluster headache is rated as low to moderate (PMID 40121062).

Tension-type headache is the most common and cluster headache is rare but the most intense, and both differ from migraine in their treatment.

When Medicine Brings on Headaches

Acute treatment medications carry a trap. Medication-overuse headache is a condition where a person who originally had headaches uses acute treatment medications so often that their headaches become frequent, occurring on 15 or more days a month. The original headache is usually a migraine or a tension-type headache, and medication-overuse headache is classified as a secondary headache caused by medication (PMID 36732518). It is estimated to affect 1 to 2% of the population (PMID 38816828). Triptans are also among the drugs that can trigger this headache (PMID 29226741). In an American observational study, the number of days that increased the risk of shifting toward more frequent headaches varied by drug class, and some classes increased the risk even with fewer days of use (PMID 22868543). Just how much use is excessive varies by drug and by person, and is evaluated together with your treating doctor.

Medication-overuse headache is closely intertwined with chronic migraine (PMID 38568489). Chronic migraine is a condition where a person has headaches on 15 or more days a month, with at least 8 of those days featuring the characteristics of a migraine. It usually develops as headaches slowly become more frequent over the course of several months to years (PMID 24662044). About 8% of people with migraines and 1 to 2% of the general population fall into this category, and episodic migraines transition to chronic ones at a rate of about 3% each year (PMID 27389092). Using acute treatment medications too frequently, acute treatments that do not work well, obesity, depression, and high life stress are cited as modifiable risk factors among them. Chronic migraines can also reverse, with about 26% of chronic migraines calming down again within two years (PMID 27389092).

Central sensitization is a state where pain circuits in the spinal cord and brain become hypersensitive, reacting more strongly to the same signals and even perceiving normally painless stimuli as painful. In medication-overuse headache, the descending control that dampens pain from above is altered, central sensitization develops, and physical and behavioral factors work together (PMID 36732518). When compared to a bell, this aligns with the earlier explanation that the more frequent the headaches, the lower the threshold at which the bell begins to ring.

Medication-overuse headache is preventable and treatable (PMID 36732518). The core of treatment is reducing or stopping the frequency of the medication that was being used too often, alongside preventive treatment. When treated properly, the effectiveness is usually very good, reducing both headaches and medication use (PMID 36732518). Because treatment includes a bridge therapy to help endure headaches during the reduction period, alongside long-term preventive treatment (PMID 15617293), which medication to reduce, when, and how is decided together with your treating doctor. A 2012 review summarized the combined treatment as establishing preventive treatment, stopping the medication that was used too frequently, and strictly limiting the days on which new acute treatment medications are used. The tapering method may be done gradually on an outpatient basis or all at once, and difficult cases may be referred to a day hospital or inpatient care (PMID 22868543). Which method to choose is also determined by your treating doctor. Education directed at both healthcare providers and patients has been effective in reducing this headache (PMID 38568489).

Taking painkillers too often can actually make headaches more frequent, and a plan to reduce those medications should be made with a doctor.

What the Records Tell Us

A headache diary is a log where you write down the days you had a headache and the days you took medication. Headache diary apps contain calendars that help track how well treatments work and find triggers (PMID 38568485). Since both chronic migraine and medication-overuse headache are defined by the number of days in a month, this record becomes information used immediately in medical exams.

Factors known to provoke migraines include stress, hormonal changes, sleep disruption, and food (PMID 40040266). Regarding factors linked to more frequent migraines, quite a bit of evidence has accumulated for things like sleep disruption and individual-specific triggers. However, studies testing whether actually avoiding or changing those factors makes migraines less frequent are rare, so the discussion relies mostly on expert opinion (PMID 37615752). The evidence gathered in this article does not support saying that any specific food triggers migraines for everyone.

Headache diaries are used to count days and medications, and tests of how much help avoiding triggers provides are still rare.

Once Again, the Painkiller in the Drawer

Let us return to the office worker from the beginning. There are headaches that tighten every afternoon and throbbing headaches a couple of times a month, and the days of taking medication have increased.

The first question is whether these headaches have signs of a secondary headache (PMID 33974014). Examples of such signs are whether it began suddenly like an explosion, whether neurological symptoms or fever accompanied it, or whether the headache pattern changed from the usual one (PMID 37456555). If such signs are present, one should promptly receive an examination and tests, and if not, the likelihood of a primary headache increases (PMID 38419454).

If it is a primary headache, a name is attached while listening to stories in the clinic (PMID 38568485). Sometimes two types of primary headaches occur together in one person, making the task of sorting out the names even trickier (PMID 37474899). If the records show that the days of taking medication are frequent, medication-overuse headache is also checked (PMID 36732518). At that time, a plan to reduce medication and preventive treatment are matters to decide together with a doctor.

As the colleague said, headaches are common, and like the scary disease names on the internet, rarely there are headaches that require urgent attention. Migraine has now firmly established itself as a treatable disease of the nervous system (PMID 41296986), and headaches that require urgency have recognizable signs.

Where to Look Next

More research is still needed on when to stop or switch medications that block CGRP, and whether they are safe when used long-term (PMID 40121062).

Conditions where blood to the brain is blocked or bursts continue in "What a Stroke Actually Is — Blocked, Burst, and the Clock", and central sensitization, where pain circuits become sensitive, in "What Is Chronic Pain? — A Microphone and an Amplifier, a Sound That Rings On Past Three Months". Disrupted sleep is covered in "Sleep Loss — A Debt Built Night by Night, Reminders That Lag Behind". How to read numbers about days reduced per month can be found in "If the Risk Was Cut in Half, How Many Fewer People Got Sick? — Relative and Absolute Risk".

The way nerve cells pass signals continues in "How Do Nerve Cells Send Signals? — A Burning Fuse, a Gap Crossed by Ferry", and the locations of the cerebral cortex and deep brain structures in "The Map of the Brain — Neighborhoods with Their Own Jobs, a City Joined by Roads". Other diseases of the brain and nerves continue in "What Is Parkinson's Disease? — An Orchestra Whose Conductor Is Fading, a First Beat That Comes In Late", "What Is Epilepsy? — Windows Lit One by One, Lights That Flash All at Once", and "Numbness and Peripheral Neuropathy — The Long Supply Line That Runs Short at the Farthest Village, the Sock That Climbs From the Toes".

Source Papers

• "The global prevalence of headache: an update, with analysis of the influences of methodological factors on prevalence estimates." (2022) — PMID 35410119 — 357 studies, mostly high-income countries, active headache 52.0%, migraine 14.0%, tension-type 26.0%, 15.8% with daily headache, temporal trends and regional differences uncertain due to methodology.
• "Diagnosis and Management of Headache: A Review." (2021) — PMID 33974014 — Lifetime prevalence in the US roughly 90%, migraine is second in YLDs, primary and secondary definitions and four primary groups, tension-type 38%, migraine 12% (studies over 100,000 people), red flags (sudden onset, neurological signs, age over 50, cancer/immunocompromised, activity/position triggered), triptans 2-hour pain-free 20–30%, side effects 25%, avoided in cardiovascular risk, preventive drugs reduce 1 to 3 days per month compared to placebo.
• "Medication overuse headache." (2023) — PMID 36732518 — Medication overuse headache is a secondary headache caused by acute medication overuse in an underlying headache (usually migraine or tension-type), ICHD-3 diagnosis, changes in descending pain modulation, central sensitization, biobehavioral factors, preventable and treatable, reducing/stopping the overused drug + preventive treatment usually very effective.
• "Headache Disorders: Differentiating Primary and Secondary Etiologies." (2024) — PMID 38419454 — Mostly primary headaches, screening for red flags is essential, high likelihood of primary headache if no red flags are present.
• "Secondary headaches - red and green flags and their significance for diagnostics." (2023) — PMID 37456555 — Secondary headaches are a small percentage but failure to differentiate worsens morbidity and mortality, red flags (sudden onset, high intensity, change in existing headache pattern, focal neurological signs/seizures, systemic signs, physical activity induced), existing headache does not rule out secondary headache.
• "Approach to the Patient With Headache." (2024) — PMID 38568485 — Headache evaluation relies heavily on history, structured history reduces accurate diagnosis and unnecessary tests, headache app calendars help track treatment response and identify triggers.
• "Thunderclap headache: an update." (2018) — PMID 30334463 — Thunderclap headache peaks within 1 minute, most concerning cause is subarachnoid hemorrhage, urgent evaluation, brain CT in all patients, lumbar puncture if non-diagnostic.
• "Evaluating thunderclap headache." (2021) — PMID 33661161 — Most common secondary cause of thunderclap headache is subarachnoid hemorrhage, second is reversible cerebral vasoconstriction syndrome, consequences of a missed diagnosis are large, justifying thorough evaluation.
• "The patient with daily headaches." (2004) — PMID 15617293 — Newly onset daily headaches, pattern changes, neurological/systemic symptoms warrant pathological causes, medication overuse treated with cessation of symptomatic drugs, transition therapy, long-term prevention.
• "Headache Emergencies." (2021) — PMID 33896523 — Mostly benign primary headaches but symptoms overlap, identify dangerous conditions with red flags and neurological exam, older age, pregnancy, immunocompromised have higher risk of secondary headaches, changing evaluation thresholds.
• "CGRP and the Trigeminal System in Migraine." (2019) — PMID 30982963 — Migraine is a strong, throbbing one-sided headache, underrecognized and undertreated, trigeminal ganglion neurons connect meningeal blood vessels and central terminals, CGRP causes and maintains peripheral sensitization and can lead to central sensitization, treatments blocking CGRP are effective.
• "Migraine without aura." (2023) — PMID 38043959 — Migraine without aura is most common, diagnosed with ICHD-3, multi-phase attack of prodrome, headache, postdrome, light/sound sensitivity, nausea, vomiting, worsened by movement are common symptoms.
• "Migraine in women: a review." (2025) — PMID 40265504 — Migraine is 2 to 3 times more common in women, and women report longer and more severe attacks.
• "Migraine." (2022) — PMID 35027572 — A chronic disorder with recurrent disabling attacks, spreading depolarization likely causes aura and triggers trigeminal activation, vasodilation is secondary and vasoconstriction is not required for efficacy.
• "Migraine with aura." (2021) — PMID 34384631 — 15% to one-third of migraine patients have aura, develops gradually, under 1 hour per symptom, fully reversible, visual aura over 90%, cortical spreading depression is the mechanism, emergency evaluation for transient ischemic attack if no visual symptoms, simultaneous onset, or vascular territory match, check for symptoms over 1 hour, late onset, rapid escalation.
• "Migraine and the trigeminovascular system-40 years and counting." (2019) — PMID 31160203 — 1979 trigeminal hypothesis, 40 years later fundamental role of trigeminovascular system broadly accepted, led to CGRP antibody treatment.
• "The Trigeminovascular Pathway: Role of CGRP and CGRP Receptors in Migraine." (2017) — PMID 28485848 — CGRP release into cranial venous outflow during migraine and cluster headache attacks, intravenous CGRP infusion induces migraine-like symptoms, led to development of CGRP-inhibiting treatments, much still unknown.
• "CGRP monoclonal antibodies and CGRP receptor antagonists (Gepants) in migraine prevention." (2024) — PMID 38307640 — CGRP is a strong vasodilator and involved in pain processing, plasma CGRP increases during and between attacks, two classes of migraine-specific first preventive drugs.
• "Chronic migraine: risk factors, mechanisms and treatment." (2016) — PMID 27389092 — Chronic migraine is 1–2% of the population, roughly 8% of migraine patients, converts about 3% per year, about 26% remission within 2 years, modifiable risk factors (acute medication overuse, ineffective acute treatment, obesity, depression, stressful life events), frequent headaches lower the attack threshold as a threshold problem.
• "Migraine: from pathophysiology to treatment." (2023) — PMID 37029836 — Migraine is complex neurobiology involving multiple regions and networks of the central and peripheral nervous systems.
• "Tension-type headache." (2021) — PMID 33767185 — Most common neurological disorder, mild to moderate, bilateral, pressing or tightening quality, not worsened by routine physical activity, diagnosed by history and exclusion of other diagnoses, divided into acute and preventive treatments.
• "Current Understanding of the Pathophysiology and Approach to Tension-Type Headache." (2021) — PMID 34599406 — Tension-type headache patients have stiffer muscles and more tenderness but causality is unclear, both peripheral and central mechanisms involved.
• "Debate: differences and similarities between tension-type headache and migraine." (2023) — PMID 37474899 — Commonalities such as onset in twenties, stress triggers, both involve trigeminovascular system, no specific tests or biomarkers, can coexist.
• "Cluster headache." (2018) — PMID 29493566 — Strictly one-sided, 15 to 180 minutes, ipsilateral tearing, conjunctival injection, female patients describe it as more painful than childbirth, hypothalamus identified as source of pain and autonomic symptoms.
• "15. Cluster Headache." (2025) — PMID 40437707 — Rare primary headache, episodic or chronic (pain-free periods less than 3 months), oxygen and subcutaneous triptans most effective abortive treatments, evidence is limited.
• "Recent advances in diagnosing, managing, and understanding the pathophysiology of cluster headache." (2024) — PMID 38876749 — CGRP-targeted antibody approved in the US as first specific preventive treatment for episodic cluster headache, not replicated in chronic cluster headache.
• "Drugs for Migraine Prophylaxis." (2026) — PMID 41572863 — Frequent or severe attacks are indication for prevention, oral preventive drugs reduce 0.44 to 1.4 days per month compared to placebo in episodic migraine with baseline 8 days per month, CGRP antibodies reduce 0.7 to 3.8 days depending on the drug, effective even in patients unresponsive to existing drugs.
• "Acute Migraine Headache: Treatment Strategies." (2025) — PMID 40238974 — Simple analgesics and NSAIDs are first-line treatment for mild to moderate attacks, triptans are first-line for moderate to severe attacks, new acute drug classes are second-line, opioid analgesic classes are not recommended.
• "Comparative effects of drug interventions for the acute management of migraine episodes in adults: systematic review and network meta-analysis." (2024) — PMID 39293828 — 137 trials, 89,445 participants, all 17 oral drugs superior to placebo for 2-hour pain-free, most effective triptans have larger effect than new drugs, caution for high cardiovascular risk.
• "Acute Treatment of Migraine." (2024) — PMID 38568487 — New acute drugs (oral CGRP-blocking class, new acute drug class) not associated with vasoconstriction or cardiovascular risk, over 20% of adults with migraine have increased cardiovascular risk, no single drug fits everyone, multiple trials needed.
• "Pharmacologic Treatments of Acute Episodic Migraine Headache in Outpatient Settings: A Clinical Guideline From the American College of Physicians." (2025) — PMID 40096690 — Strong recommendation (moderate certainty) to add triptans for non-pregnant adults with insufficient response to NSAIDs.
• "Calcitonin gene-related peptide-targeting therapies are a first-line option for the prevention of migraine: An American Headache Society position statement update." (2024) — PMID 38466028 — Existing first-line preventive drugs developed for other indications, substantial evidence for CGRP-targeted therapy, serious adverse reactions rare, considered as first-line prevention even without failure of other drugs.
• "Calcitonin gene-related peptide-targeted therapy in migraine: current role and future perspectives." (2025) — PMID 40121062 — CGRP-targeted antibodies since 2018, first drugs designed specifically for migraine prevention, low to moderate efficacy in cluster headache, long-term safety, cost-effectiveness, discontinuation, and switching studies needed.
• "The comparative effectiveness of migraine preventive drugs: a systematic review and network meta-analysis." (2023) — PMID 37208596 — 74 trials, 32,990 participants, CGRP antibodies, oral CGRP-blocking drugs, and an antiseizure medication class increase the rate of 50% or greater reduction (high certainty), CGRP class does not increase discontinuations due to adverse events, CGRP antibodies have highest efficacy and safety profile, oral CGRP-blocking drugs closely behind.
• "Calcitonin gene-related peptide (CGRP): role in migraine pathophysiology and therapeutic targeting." (2020) — PMID 32003253 — CGRP-targeted drugs relieve symptoms in half of patients while the other half do not respond, safety is exceptional.
• "CGRP and Migraine: Real-World Insights and Future Therapeutic Directions." (2026) — PMID 41296986 — Remarkably safe so far, but some adverse events are being revealed.
• "CGRP-Targeted Migraine Therapies in Patients With Vascular Risk Factors or Stroke: A Review." (2025) — PMID 40537071 — Cardiovascular safety appears favorable in patients without major risk factors, but data for patients with preexisting vascular disease or recent vascular events are sparse and long-term effects remain a concern.
• "Setting higher standards for migraine prevention: A position statement of the International Headache Society." (2025) — PMID 39980456 — 50% reduction in monthly migraine days may not fully restore quality of life, proposing absolute targets based on remaining days.
• "Medication-overuse headache: a narrative review." (2024) — PMID 38816828 — Defined as 1–2% of population, headache 15 or more days per month + acute medication overuse, patient education is core, preventable.
• "Side effects associated with current and prospective antimigraine pharmacotherapies." (2018) — PMID 29226741 — Ergot class and triptans can cause medication overuse headache, triptan side effects (nausea, dizziness, coronary vasoconstriction).
• "Medication-Overuse Headache." (2024) — PMID 38568489 — Prevalence 1–2%, closely tied to chronic migraine, reduction/cessation of overused drugs and preventive treatment, clinician and patient education effective.
• "Chronic migraine." (2014) — PMID 24662044 — 2% of population, headache 15 or more days per month with at least 8 days meeting migraine criteria, frequency gradually increases over months to years.
• "Mechanistic approach and therapeutic strategies in menstrual and non-menstrual migraine." (2025) — PMID 40040266 — Stress, hormonal changes, sleep disturbances, diet, gut health cited as triggers.
• "Risk factors for migraine disease progression: a narrative review for a patient-centered approach." (2023) — PMID 37615752 — Progression risk factors (optimized acute treatment not achieved, acute medication overuse, sleep disturbances, personal triggers, etc.), protective behaviors preventing progression hardly studied, relying on expert opinion, interventional studies needed.
• "Aseptic and Bacterial Meningitis: Diagnosis, Treatment, and Prevention." (2026) — PMID 41839077 — Meningitis is inflammation of the membranes wrapping the brain, adults and older children may present with neck stiffness, fever, headache, altered consciousness, center of diagnosis is lumbar puncture.
• "Medication-overuse headache." (2012) — PMID 22868543 — Frequent acute medications convert headache to 15 or more days a month, US observational study (AMPP) shows conversion-prone days differ by drug class, some classes increase risk with minor use, treatment is preventive treatment + stopping overused drugs + strict restriction of new acute drugs, outpatient slowly or at once, or day hospital/admission if difficult.
• "[Non-medical Approaches to Headache Prevention: What is the Evidence?]." (2024) — PMID 38885654 — Among non-pharmacological preventions, only cognitive behavioral therapy and biofeedback have established evidence, aerobic endurance exercise has best evidence for migraine prevention, combining non-pharmacological with drug prevention recommended.