METHODS: A "two-hit" priming model of
medication overuse headache was used. Female Sprague-Dawley rats received six oral doses of
sumatriptan 10 mg/kg over 2 weeks to induce latent sensitization (i.e. "priming"). Cutaneous
allodynia was measured periodically over 20 days in the periorbital and hindpaw regions using von Frey filaments. The rats were then subjected to a 1-hour bright light stress challenge on two consecutive days. At the start of the second bright light stress exposure, oral
sumatriptan 10 mg/kg, oral
ubrogepant 25, 50, or 100 mg/kg, or vehicle was administered; thereafter, cephalic and hindpaw sensory thresholds were monitored hourly over 5 hours to determine the efficacy of
ubrogepant in reversing bright light stress-induced cutaneous
allodynia. A dose of
ubrogepant effective in the
medication overuse headache model (100 mg/kg) was then selected to determine if repeated administration would produce latent sensitization. Rats were administered six oral doses of
ubrogepant 100 mg/kg,
sumatriptan 10 mg/kg (positive control), or vehicle over 2 weeks, and cutaneous
allodynia was evaluated regularly. Testing continued until mechanosensitivity returned to baseline levels. Rats were then challenged with bright light stress on days 20 and 21, and periorbital and hindpaw cutaneous
allodynia was measured. On days 28 to 32, the same groups received a
nitric oxide donor (
sodium nitroprusside 3 mg/kg, i.p.), and cutaneous
allodynia was assessed hourly over 5 hours.
RESULTS: CONCLUSIONS: