title: Acetylsalicylic acid inhibits cerebral cortical vasodilatation caused by superior sagittal sinus stimulation in the cat*.
abstract: Acetylsalicylic acid (ASA; aspirin) is one of the most widely used pain reliefs in the world and is certainly effective in the treatment of acute attacks of migraine of moderate severity. It has usually been considered that the action of ASA in migraine is related to peripheral inhibition of mediators of inflammation. Migraine involves episodic head pain that is thought generally to involve intracranial pain structures innervated by the ophthalmic (first) division of the trigeminal nerve, particularly vascular structures that have come to be known as the trigeminovascular system. In this study the effect of ASA on the cerebrovascular effects of the trigeminovascular system were assessed directly with measurements of cerebral blood flow. The trigeminovascular system was activated by stimulation of the superior sagittal sinus (SSS), a midline large venous sinus that is pain sensitive in humans. The SSS was stimulated electrically and cerebral blood flow measured using laser Doppler flowmetry (CBFLDF ). Stimulation of the SSS resulted in a stimulus-locked frequency-dependent increase in CBFLDF that reached a mean maximum at 2 Hz with a 60 ± 6% reduction in calculated cerebrovascuiar resistance. Administration of ASA (30 mg/kg i.v.) resulted in a small non-sustained increase in blood pressure but no change in resting CBFLDF . The CBFLDF response to SSS stimulation was reduced at all but one frequency of stimulation to a maximum of a 43 ± 10% reduction in cerebrovascular resistance. Since electrical stimulation involves consecutive depolarization of trigeminovascular axons and bypasses the peripheral nerve vessel interaction it is likely that this effect of ASA is mediated in the central nervous system. Such a possibility draws attention to a possibly novel therapeutic locus of action for ASA and to the importance of central nervous system processing of trigeminovascular inputs that are integral to the clinical expression of migraine.
authors.affiliation: Department of Neurology, The Prince Henry Hospital, Little Bay, Sydney, NSW 2036, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Kaube
authors.forename: K L
authors.initials: KL
authors.lastname: Hoskin
authors.forename: P J
authors.initials: PJ
authors.lastname: Goadsby