title: Oxygen inhibits neuronal activation in the trigeminocervical complex after stimulation of trigeminal autonomic reflex, but not during direct dural activation of trigeminal afferents.
abstract: OBJECTIVE
  To understand the mechanism of action of oxygen treatment in cluster headache.
  
  
  BACKGROUND
  Trigeminal autonomic cephalalgias, including cluster headache, are characterized by unilateral head pain in association with ipsilateral cranial autonomic features. They are believed to involve activation of the trigeminovascular system and the parasympathetic outflow to the cranial vasculature from the superior salivatory nucleus (SuS) projections through the sphenopalatine ganglion, via the greater petrosal nerve of the VIIth (facial) cranial nerve. Cluster headache is remarkably responsive to treatment with oxygen, and yet our understanding of its mode of action is unknown.
  
  
  METHODS
  Combining models of trigeminovascular nociception and a novel approach that activates the trigeminal-autonomic reflex, using SuS/facial nerve stimulation, we explored the effect of oxygen on trigeminal nerve activation as well as on autonomic responses through blood flow observations of the lacrimal duct/sac.
  
  
  RESULTS
  Meningeal vasodilation and neuronal firing in the trigeminocervical complex (TCC), in response to dural electrical stimulation, was unaffected by treatment with 100% oxygen. Stimulation of the SuS via the facial nerve caused only marginal changes in dural blood vessel diameter, but did result in evoked firing in the TCC. Two populations of neurons were characterized, those responsive to 100% oxygen treatment, with a maximal inhibition of 33%, 20 minutes after the start of oxygen treatment (t(15) = 4.4, P < .0001). A second population of neurons were not inhibited by oxygen and tended to have shorter latency. Oxygen also inhibited evoked blood flow changes in the lacrimal sac/duct caused by SuS stimulation.
  
  
  CONCLUSIONS
  The data provide the first systematic, experimental evidence for a mechanism of action of oxygen in cluster headache. The data show oxygen has no direct effect on trigeminal afferents, acting specifically on the parasympathetic/facial nerve projections to the cranial vasculature to inhibit both evoked trigeminovascular activation and activation of the autonomic pathway during cluster headache attacks. Moreover, the studies begin to characterize a novel laboratory model for the most painful primary headache syndrome known--cluster headache.
authors.affiliation: Headache Group, Department of Neurology, University of California, San Francisco, San Francisco, CA 94143-0114, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Akerman
authors.forename: Philip R
authors.initials: PR
authors.lastname: Holland
authors.forename: Michele P
authors.initials: MP
authors.lastname: Lasalandra
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goadsby
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002536:Cerebral Arteries / Q000294:innervation / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D003027:Cluster Headache / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004388:Dura Mater / Q000503:physiopathology; D004558:Electric Stimulation / Q000009:adverse effects; D005154:Facial Nerve / Q000033:anatomy & histology / Q000503:physiopathology; D008297:Male; D010100:Oxygen / Q000494:pharmacology* / Q000627:therapeutic use; D010275:Parasympathetic Nervous System / Q000033:anatomy & histology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012021:Reflex, Abnormal / Q000187:drug effects* / Q000502:physiology; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects* / Q000503:physiopathology; D014276:Trigeminal Nerve / Q000187:drug effects* / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D010100:Oxygen