The search for non-evoked markers of pain in the GTN mouse model of migraine.

Rodent migraine models have been developed to study the underlying molecular mechanisms of migraine, but these need further development and validation to stay relevant. The glyceryl trinitrate (GTN) mouse model with tactile hypersensitivity as the primary readout, has been highly used to understand the pathophysiology of migraine. Nevertheless, this readout has questionable translatability to the experience of spontaneous pain and additional readouts are needed to improve this model. We explored the applicability of several spontaneous behaviours and burrowing activity as additional markers to detect effects of repeated GTN injections in mice. We used the Laboratory Animal Behaviour Observation Registration and Analysis System (LABORAS) test system to understand the potential effect of GTN on locomotion and other behavioral parameters in two different experiments. Burrowing was used to investigate the potential effect on GTN on a voluntary innate behavior of mice. We found no clear effect of GTN on either locomotion or burrowing in these experiments. With our experimental design, there was no significant difference between GTN and vehicle and neither locomotion nor burrowing activity will readily supplement the von Frey test. The search for additional none-evoked markers of pain in rodent migraine models will continue.