Investigation of Nocifensive and Cellular Effects of Dihydroergotamine in a Model of Chronic Migraine
Date of Graduation
Master of Science in Biology
The goal of my study was to investigate the nocifensive behavioral and cellular effects of dihydroergotamine (DHE) and sumatriptan in a model of sustained trigeminal activation. Trigeminal nerves provide sensory innervation to the head and face and their activation has been implicated in migraine pathology. The most commonly prescribed medications for migraine treatment are the triptan class of drugs. However, triptans are not an effective therapy for all migraine patients and some develop triptan resistance. Ergot-derivatives, including DHE, could be a potential alternative for this subpopulation of patients. To cause activation of the trigeminal system, adult male Sprague Dawley rats were given an inflammatory injection of complete Freund's adjuvant (CFA) or saline as a vehicle control in the temporomandibular joint capsule. Three and four days post-CFA-injection, intraperitoneal injections of DHE, sumatriptan, or vehicle control were delivered. I found that DHE, but not sumatriptan, was able to transiently inhibit CFA-mediated increases in nocifensive withdrawal behavior. Within the spinal cord, DHE was shown to inhibit CFA stimulated levels of the signaling protein PKA, which is known to promote central sensitization, and Iba1, a marker of activated microglial cells. However, both DHE and sumatriptan were able to inhibit stimulated levels of GFAP, a protein used as a marker of activated astrocytes. Results from my study provide evidence that DHE, but not sumatriptan, can inhibit nociception caused by prolonged activation of trigeminal neurons and the inhibitory effect is likely to involve suppressing development of central sensitization. I propose that DHE may be therapeutically beneficial by blocking ongoing peripheral and central sensitization as characteristic of frequent episodic and chronic migraine.
migraine, trigeminal, central sensitization, inflammation, nociception
© Jennifer Elise Denson
Denson, Jennifer Elise, "Investigation of Nocifensive and Cellular Effects of Dihydroergotamine in a Model of Chronic Migraine" (2015). MSU Graduate Theses. 1350.