Extracranial origin of headache

Purpose of review To summarize recent clinical and preclinical studies on extracranial pathophysiologies in migraine. It challenges the opinion-based notion that the headache phase of migraine occurs without input from peripheral nociceptors or is caused solely by activation of intracranial nociceptors supplying dural and cerebral vasculature. Recent findings Data that support a scenario by which migraine can originate extracranially include the perception of imploding headache that hurts outside the cranium, the existence of a network of sensory fibers that bifurcate from parent axons of intracranial meningeal nociceptors and reach extracranial tissues such as periosteum and pericranial muscles by crossing the calvarial bones through the sutures, the discovery of proinflammatory genes that are upregulated and anti-inflammatory genes that are down regulated in extracranial tissue of chronic migraine patients, and evidence that administration of OnabotulinumtoxinA to peripheral tissues outside the calvaria reduces frequency of migraine headache. Summary These findings seeks to shift clinical practice from prophylactically treating chronic migraine solely with medications that reduce neuronal excitability to treating irritated nociceptors or affected tissues. The findings also seeks to shift current research from focusing solely on central nervous system alterations and activation of meningeal nociceptors as a prerequisite for studying migraine.