Role of transient receptor potential ankyrin 1 in light aversion of mice

Transient receptor potential ankyrin 1 (TRPA1) plays a pivotal role in migraine pathogenesis via regulating cortical spreading depression, neuroinflammation, hyperalgesia and trigeminovascular system activation and sensitization. However, whether TRPA1 could affect photophobia, a symptom that affects ~80% migraineurs, is unknown. In this study, we examined whether TRPA1 activation triggers photophobia, and displays a gender-specific difference in photophobia behavior. C57BL/6J mice were used to assess mouse behavior in both dark and light compartments of a chamber. The photophobia behavior was triggered by intranasal injection of the volatile TRPA1 activator umbellulone. After umbellulone or its vehicle was injected, total time spent in the light area and the transition times were analyzed at 30 minutes post-intranasal injection. The results showed that umbellulone significantly reduced total time in light and transition times in both male and female mice when respective control was compared. All mice showed reduced total time in light and transition times with full response rate indicating the drug a wide spectrum of inducing photophobia. The umbellulone-induced acute light aversion behavior did not display gender-specific difference, albeit in the control group, female mice were more sensitive than male to the intranasal injection of the vehicle with a marked reduction of the total time in light compared to control. The rapid onset and injury-free mouse model of photophobia by umbellulone is a significant contribution, not only offering new insights into the pivotal role of TRPA1 in migraine pathogenesis, but also presenting alternative photophobia models that are devoid of injury and exhibit a rapid-onset.