Abnormal trigeminal sensory processing in obese mice

Obesity is associated with several pain disorders including headache. The effects of obesity on the trigeminal nociceptive system, which mediates headache, remain unknown. We used 2 complementary mouse models of obesity (high-fat diet and leptin deficiency) to examine this. We assessed capsaicin-induced nocifensive behavior and photophobia in obese and control mice. Calcium imaging was used to determine the effects of obesity on the activity of primary trigeminal afferents in vitro. We found that obese mice had a normal acute response to a facial injection of capsaicin, but they developed photophobic behavior at doses that had no effect on control mice. We observed higher calcium influx in cultured trigeminal ganglia neurons from obese mice and a higher percentage of medium to large diameter capsaicin-responsive cells. These findings demonstrate that obesity results in functional changes in the trigeminal system that may contribute to abnormal sensory processing. Our findings provide the foundation for in-depth studies to improve the understanding of the effects of obesity on the trigeminal system and may have implications for the pathophysiology of headache disorders.