Origin of pain in migraine: evidence for peripheral sensitisation

Migraine is the most common neurological disorder affecting millions worldwide. Recent research has shed light on its complex mechanisms. The origin of pain in the trigeminal nerve remains uncertain, despite extensive study. While central sensitisation has received much attention, peripheral nociceptor activation seems crucial. Interestingly, migraine attacks might begin in deep-brain structures. However, the headache phase likely relies on signals from perivascular sensory nerve terminals. Evidence suggests that input from arteries plays a significant role, potentially more than that from veins. Studies indicate nociceptive input from extracranial, dural, and pial arteries. However, findings also challenge the significance of these areas. Ultimately, the activation of afferents likely occurs across all three regions. The importance of each area may vary among patients. Therefore, migraines can be explained as brain disorders, with headaches stemming from sensory fibres conveying pain signals. Clinical relevance: This research highlights the role of peripheral nerves in migraine pain, guiding better treatment approaches.