A headache is a complex neurobiological event involving dramatic, measurable shifts in brain activity. While the experience is centered on an intense physical feeling, the underlying cause is not structural damage or injury within the brain. Instead, the pain represents a temporary malfunction in the brain’s processing and pain-signaling systems. This perspective focuses on how the brain’s function, chemistry, and electrical patterns change during an attack.
Structural Stability Versus Functional Change
Standard medical imaging, such as computed tomography (CT) or conventional magnetic resonance imaging (MRI), typically reveals a structurally normal brain during a headache. These structural scans are designed to detect physical issues like tumors, bleeding, or swelling, which are not the cause of primary headaches. The internal architecture of the brain, including its gray and white matter, remains physically intact throughout the episode.
The changes that define a headache are functional, involving alterations in how the brain operates and communicates. Advanced functional imaging techniques, including functional MRI (fMRI) and Positron Emission Tomography (PET) scans, capture these dynamic shifts. These scans track changes in blood flow, electrical activity patterns, and neurotransmitter release, providing a map of the brain’s functional disarray during an attack. The headache experience is a manifestation of temporarily altered brain chemistry and electrical signaling.
The Unique Neurological Events of Migraine
Migraine attacks feature the most pronounced functional changes, often originating from a region deep within the brainstem. This area, sometimes referred to as the “migraine generator,” includes nuclei like the locus coeruleus and dorsal raphe nucleus, which modulate arousal, mood, and pain. Activation in this brainstem area can be detected hours or even days before the onset of pain, corresponding with the premonitory phase.
A distinct phenomenon tied to migraine with aura is Cortical Spreading Depression (CSD), a slow wave of profound change in electrical activity that propagates across the cerebral cortex. CSD begins with a burst of intense neuronal activity followed by a prolonged period of electrical silence, traveling across the brain’s surface at a rate of about two to five millimeters per minute. This spreading wave is strongly linked to the visual and sensory disturbances that characterize the aura phase, such as shimmering zig-zag lines or blind spots. The electrical wave of CSD is immediately followed by a change in local blood flow: a brief increase followed by sustained oligemia, or reduced blood flow.
The Trigeminal System and Pain Signal Initiation
Regardless of the headache type, the sensation of pain is routed through the Trigeminal Vascular System (TVS). This system consists of sensory fibers of the trigeminal nerve that innervate the pain-sensitive structures of the head, most notably the meninges, the protective layers surrounding the brain. The fibers of the TVS wrap around the blood vessels, particularly the meningeal arteries.
When these trigeminal nerves are activated, they release potent chemical messengers, primarily Calcitonin Gene-Related Peptide (CGRP). CGRP acts as a powerful vasodilator, causing blood vessels to expand and inducing a localized inflammatory response in the meninges. This neurogenic inflammation and subsequent changes in the blood vessel wall contribute to the throbbing sensation associated with intense headache pain. The release of CGRP also sensitizes the surrounding nerve endings, making them more reactive to pain signals and intensifying the headache experience.
Central Processing: Mapping Headache Pain in the Brain
Once the pain signal is initiated, it travels into the brainstem where it is first processed in the Trigeminal Nucleus Caudalis (TNC). The TNC acts as the initial gatekeeper for all craniofacial pain signals before sending them upward. From the brainstem, the signal is routed to the Thalamus, the brain’s central sensory switchboard, which relays the incoming pain information to the appropriate cortical regions.
The final destination for the conscious perception of pain is the Somatosensory Cortex, where the location, intensity, and quality of the headache are registered and mapped. Functional imaging also shows activation in the Limbic System, including the amygdala and cingulate cortex. This involvement is responsible for associated symptoms like emotional distress, nausea, and heightened sensitivity to light and sound.
How Different Headache Types Differ Neurologically
The primary headache types—migraine, tension, and cluster—each have distinct neurological signatures, though they share the common pain pathway of the trigeminal system. Migraine is characterized by Cortical Spreading Depression (CSD) and the pronounced activation of the trigeminal system with CGRP release. This combination explains the intense, multi-symptom nature of the attacks.
Tension-type headaches, which are generally milder, appear linked to a heightened sensitivity of the central pain pathways and sustained low-level activation of the trigeminal system. They often occur without the unique CSD event seen in migraine. The mechanism is thought to involve increased muscle tension and generalized hypersensitivity.
In contrast, Cluster headaches have a strong connection to the Hypothalamus, the brain region that regulates the body’s internal clock. Activation near the hypothalamus is strongly associated with Cluster attacks, explaining their cyclical, time-locked, and seasonal patterns. This hypothalamic driver also triggers the intense autonomic symptoms—such as a drooping eyelid, tearing, and nasal congestion—that define Cluster headaches.