Headaches

Mechanism: The leading model involves Cortical Spreading Depression (CSD), a wave of intense neural activity followed by suppression, which is linked to aura and triggers the trigeminovascular system. This activation releases neuropeptides like Calcitonin Gene-Related Peptide (CGRP), leading to neurogenic inflammation, vasodilation, and the severe, often unilateral, throbbing pain characteristic of migraine. The brainstem and hypothalamus are also involved, modulating pain sensitivity and contributing to premonitory symptoms.

Prognosis: Migraine is typically a chronic condition with episodic attacks that can vary in frequency and severity. For some, frequency can increase over time, transitioning to chronic migraine (≥15 headache days per month). Onset is most common before age 40.

Treatment:

• Acute: Triptans (e.g., Rizatriptan), which are 5-HT1B/1D receptor agonists, work by constricting cranial blood vessels and inhibiting neuropeptide release. Due to their vasoconstrictive action, they are contraindicated in patients with cardiovascular disease. Newer options include “gepants” (oral CGRP receptor antagonists) and “ditans” that target the 5-HT1F receptor without causing vasoconstriction.
• Preventive: For frequent attacks, options include beta-blockers, antidepressants, anti-seizure medications, and the CGRP-targeted monoclonal antibodies and gepants.

Mechanism: The pathophysiology is multifactorial and not fully resolved, i.e. we don’t really know. It is thought to involve both peripheral and central mechanisms. In episodic TTH, peripheral factors like increased pericranial muscle tenderness are key. In chronic TTH, central sensitization of pain pathways in the central nervous system (CNS) appears more dominant, meaning the CNS becomes more efficient at processing pain signals.

Prognosis: The prognosis is generally good. Episodic TTH can often be managed with simple analgesics and lifestyle adjustments. A subset of individuals may develop chronic TTH, which can be more debilitating and challenging to treat.

Treatment:

• Acute: Simple analgesics like NSAIDs (ibuprofen, naproxen) and acetaminophen are the first line of treatment. Limiting use to twice a week is crucial to avoid medication-overuse headache.
• Preventive: For chronic TTH, the tricyclic antidepressant amitriptyline is a well-established prophylactic treatment. Non-pharmacological approaches, including physical therapy, stress management, and cognitive behavioral therapy, are also central to management.

Mechanism: While the exact cause is unknown, imaging studies point to the hypothalamus as a key player, explaining the remarkable circadian and circannual periodicity of attacks (occurring at the same time of day or year). This hypothalamic activation leads to secondary activation of the trigeminal and cranial autonomic systems, causing the characteristic pain and accompanying symptoms like a watering eye, nasal congestion, and a sense of restlessness or agitation.

Prognosis: About 90% of individuals have episodic cluster headache, with periods of frequent attacks (“clusters”) lasting weeks to months, followed by remission periods. The remaining 10% have the chronic form, with no significant remission. The pain is considered one of the most severe known to medicine.

Treatment:

• Acute: The two mainstays are high-flow oxygen (100% O2 via a non-rebreather mask), which is effective for most patients within 15 minutes, and injectable or nasal triptans.
• Preventive: Verapamil, a calcium channel blocker, is the first-line prophylactic treatment. For transitional periods, greater occipital nerve blocks can provide relief. Newer options include the CGRP monoclonal antibody galcanezumab.