Terminating Migraine With Allodynia and Ongoing Central Sensitization Using Parenteral Administration of COX1/COX2 Inhibitors

The study's objective is to determine whether delayed infusion of COX1/COX2 inhibitors will stop migraine in patients, and suppress ongoing sensitization in central trigeminovascular neurons in rats. Migraine patients were divided in two groups of 14 each: group 1 received delayed sumatriptan injection 4 hours after onset of attack, which failed to render them pain free-and ketorolac infusion 2 hours later. Group 2 received delayed ketorolac monotherapy 4 hours after onset of attack.

Pain intensity and skin sensitivity were measured when the patients were migraine free; 4 hours after onset of migraine (just before treatment); 2 hours after sumatriptan; 1 hour after ketorolac. In the rat, the researchers tested whether ketorolac or indomethacin will block ongoing sensitization in peripheral and central trigeminovascular neurons. Seventy-one percent and 64% of the patients in groups 1 and 2, respectively, were rendered free of pain and allodynia within 60 minutes of ketorolac infusion. Nonresponders from both groups, in contrast to the responders, had had a history of opioid treatment. In the rat, infusion of COX1/COX2 inhibitors blocked sensitization in meningeal nociceptors and suppressed ongoing sensitization in spinal trigeminovascular neurons.

The researchers concluded that termination of migraine with ongoing allodynia using COX1/COX2 inhibitors is achieved through the suppression of central sensitization. Although impractical as routine migraine therapy, parenteral administration of COX1/COX2 inhibitors should be the rescue therapy of choice for patients seeking emergency care for migraine. These patients should never be treated with opioids, particularly if they had no prior opioid exposure. Jakubowski M, Levy D, Goor-Aryeh I, Collins B, Bajwa Z, Burstein R. Adapted from Headache 2005;45:850-861.

PMID: 15985101