title: Extracranial origin of headache.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: aDepartment of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center bDepartment of Anesthesia, Harvard Medical School, Boston, Massachusetts cHeadache Center of Greater Heights, Memorial Hermann Medical Group dRiver Oaks Plastic Surgery Center, Houston, Texas, USA.
authors.forename: Rami
authors.initials: R
authors.lastname: Burstein
authors.forename: Pamela
authors.initials: P
authors.lastname: Blake
authors.forename: Aaron
authors.initials: A
authors.lastname: Schain
authors.forename: Carlton
authors.initials: C
authors.lastname: Perry
mesh_terms: D019274:Botulinum Toxins, Type A / Q000627:therapeutic use; D020773:Headache Disorders / Q000209:etiology* / Q000503:physiopathology* / Q000517:prevention & control; D006801:Humans; D008881:Migraine Disorders / Q000209:etiology* / Q000503:physiopathology* / Q000517:prevention & control; D009465:Neuromuscular Agents / Q000627:therapeutic use
chemical_list: D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A