Indomethacin has no effect on trigeminally provoked parasympathetic output

BACKGROUND: Unlike other non-steroidal anti-inflammatory drugs, indomethacin has been shown to be highly effective in two forms of trigeminal autonomic cephalalgias, hemicrania continua and paroxysmal hemicrania and in some forms of idiopathic stabbing headaches. This specificity is unique in the headache field. Previous findings suggest the involvement of the trigeminal autonomic reflex to play an important role in the pathophysiology of these diseases. METHODS: 22 healthy participants were enrolled in a double-blind, three-day within-subject design. The participants received indomethacin, ibuprofen or placebo in a randomized order. After an incubation period of 65 min the baseline lacrimation and the lacrimation during intranasal stimulation evoked by kinetic oscillation stimulation were assessed using Schirmer II lacrimation tests. The lacrimation difference in mm was calculated and compared in a repeated measures ANOVA. RESULTS: No significant differences were found between the three conditions. CONCLUSION: In our study, neither indomethacin nor ibuprofen had an inhibitory effect on the trigeminal autonomic reflex. We suggest that blocking this reflex may not be the treatment mechanism of indomethacin.