Abstract
BackgroundThe development of new anti-migraine treatments is limited by the difficulty inassessing migraine pain in laboratory animals. Depression of activity is one of the few diagnostic criteria formigraine that can be mimicked in rats. The goal of the present study was to test the hypothesis thatdepression of home cage wheel running is a reliable and clinically relevant method to assess migraine painin rats.MethodsAdult female rats were implanted with a cannula to inject allyl isothiocyanate (AITC) onto the dura to induce migraine pain, as has been shown before. Rats recovered from implantation surgery for 8 days in cages containing a running wheel. Home cage wheel running was recorded 23 h a day. AITC and the migraine medication sumatriptan were administered in the hour prior to onset of the dark phase.ResultsAdministration of AITC caused a concentration-dependent decrease in wheel running that lasted 3 h. The duration and magnitude of AITC-induced depression of wheel running was consistent following three repeated injections spaced 48 h apart. Administration of sumatriptan attenuated AITC-induced depressionof wheel running when a large dose (1 mg/kg) was administered immediately following AITC administration. Wheel running patterns did not change when sumatriptan was given to naïve rats.ConclusionsThese data indicate that home cage wheel running is a sensitive, reliable, and clinically relevant method to assess migraine pain in the rat.
Highlights
The development of new anti-migraine treatments is limited by the difficulty inassessing migraine pain in laboratory animals
Experiment 1: allyl isothiocyanate (AITC) concentration-response Microinjection of AITC onto the dura caused a concentration-dependent reduction in wheel running
The highest concentration of AITC (10%) caused a pronounced depression of wheel running that lasted for 3 h (Fig. 1a)
Summary
The development of new anti-migraine treatments is limited by the difficulty inassessing migraine pain in laboratory animals. A number of studies have used depression of activity (e.g., locomotor activity, feeding, rearing) to assess pain resulting from headache in humans [18] and rodents [7, 9, 17, 20, 28]. The problem with these studies is that assessment was limited to 60 min or less making it impossible to quantify the full duration and magnitude of the migraine. The time course for the headache phase of migraine can last from 4 to 72 h
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