Indomethacin and acetylsalicylic acid block neurogenic plasma protein extravasation in rat dura mater.
Leakage of 125I-bovine serum albumin was measured in rat dura mater, conjunctiva, eyelid and lip, after unilateral electrical stimulation of the trigeminal ganglion. In one animal, 99Tc-human serum albumin leakage was imaged in ipsilateral facial tissues. Pretreatment with indomethacin 1 mg/kg i.p. decreased leakage in dura mater but not in extracranial tissues. When extravasation was expressed as a ratio of stimulated to unstimulated sides, indomethacin 1 mg/kg, or acetylsalicylic acid 50 mg/kg decreased this ratio from 1.80 to 1.27 (P less than 0.01) or from 1.84 to 1.21 (P less than 0.01), respectively. Dexamethasone (1 mg/kg i.p. tid X 1 day) caused only a very small decrease. Only large doses of indomethacin (10 mg/kg) or acetylsalicylic acid (50 mg/kg) reduced substance P (SP)-induced leakage in the dura. The latter results suggest that both drugs block plasma extravasation by acting on neuropeptides-induced changes in vascular permeability and/or smooth muscle contractility. However, inhibition of SP release from sensory axons cannot be excluded at concentrations which block neurogenic plasma extravasation but not SP-induced plasma leakage. Together, these results provide a possible mechanism for the therapeutic effects of indomethacin and acetylsalicylic acid in headache.
Department of Surgery, Massachusetts General Hospital, Harvard Medical School Boston, MA 02114.
M G
MG
Buzzi
D E
DE
Sakas
M A
MA
Moskowitz
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001798:Blood Proteins / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004388:Dura Mater / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D005119:Extravasation of Diagnostic and Therapeutic Materials; D005260:Female; D005724:Ganglia / Q000187:drug effects / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D009420:Nervous System / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013668:Technetium Tc 99m Aggregated Albumin; D014276:Trigeminal Nerve / Q000187:drug effects
D001798:Blood Proteins; D013668:Technetium Tc 99m Aggregated Albumin; D003907:Dexamethasone; D015232:Dinoprostone; D001241:Aspirin; D007213:Indomethacin