title: Indomethacin, alone and combined with prochlorperazine and caffeine, but not sumatriptan, abolishes peripheral and central sensitization in in vivo models of migraine.
abstract: Recently it has been proposed that the throbbing pain of migraine is mediated by sensitization of peripheral trigeminovascular neurons, and that cutaneous allodynia of migraine is mediated by sensitization of central trigeminovascular neurons, and, moreover, that the triptans are less effective in aborting a migraine attack if the central sensitization is already established. The combination of indomethacin, prochlorperazine, and caffeine (IndoProCaf) is a drug of well-established use in the acute treatment of migraine. The aim of this study was to investigate whether the 3 active principles of IndoProCaf, alone and combined, compared to sumatriptan, were able to abolish the peripheral sensitization induced by kainic acid and the central sensitization induced by N-methyl-D-aspartate (NMDA) in in vivo models of hyperalgesia. The study showed that indomethacin or IndoProCaf is able to abolish both the kainic acid-induced and the NMDA-induced hyperalgesia. If administered at different times, IndoProCaf was always effective in reversing the kainic acid-induced hyperalgesia. Sumatriptan was not able to reverse either the kainic acid-induced or the NMDA-induced hyperalgesia. The efficacy of indomethacin, alone and combined with prochlorperazine and caffeine, in abolishing peripheral and central sensitization in in vivo models of hyperalgesia is a further explanation of the clinical efficacy of IndoProCaf in the treatment of migraine.
  
  
  CONCLUSIONS
  This study suggests that, although triptans were shown to be able to abort migraine attacks only if given before the establishment of cutaneous allodynia and central sensitization, IndoProCaf should be able to abort migraine attacks independently from the time of administration, because it is able to abolish an already established peripheral and central sensitization.
authors.affiliation: Department of Preclinical and Clinical Pharmacology, University of Florence, Firenze, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Ghelardini
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Galeotti
authors.forename: Irene
authors.initials: I
authors.lastname: Grazioli
authors.forename: Carla
authors.initials: C
authors.lastname: Uslenghi
mesh_terms: D000818:Animals; D002110:Caffeine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D007213:Indomethacin / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008881:Migraine Disorders / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D010525:Peripheral Nerves / Q000187:drug effects / Q000502:physiology; D011346:Prochlorperazine / Q000008:administration & dosage*; D018170:Sumatriptan / Q000008:administration & dosage*; D014276:Trigeminal Nerve / Q000187:drug effects / Q000502:physiology
chemical_list: D002110:Caffeine; D018170:Sumatriptan; D007213:Indomethacin; D011346:Prochlorperazine