Female sex and obesity increase photophobic behavior in mice

Abstract

Migraine affects predominantly women. Furthermore, epidemiological studies suggest that obesity is a risk factor for migraine and this association is influenced by sex. However, the biological basis for this bias is unclear. To address this issue, we assessed light avoidant behavior, a surrogate of photophobia, in female C57BL/6J mice fed regular diet (RD) or high fat diet (HFD, 60% kcal from fat). We first assessed sex differences in basal photophobia in 20-25 week old mice and found that both obese and lean females spent significantly less time in light than their male counterparts. Next, we assessed photophobia evoked by trigeminal stimulation with intradermal capsaicin. Females at 20-25 weeks of age did not display capsaicin-evoked photophobic behavior unless they had diet-induced obesity. When we tested 8-11 week old females to determine if the diet alone could be responsible for this effect, we found that both HFD and RD 8-11 week old females exhibit capsaicin-evoked photophobic behavior. This is in contrast to what we have previously shown in males and indicates a sex difference in the photophobic behavior of mice. Comparison of 20-25 week old RD mice with 8-11 week old RD mice suggests that age or age-related weight gain may contribute to capsaicin-evoked photophobic behavior in males, but not in females. These findings suggest that obesity exacerbates photophobia in both sexes, but additional work is needed to understand the sex- and age-specific mechanisms that may contribute to photophobia and trigeminal pain.

Frequent mild head injury promotes trigeminal sensitivity concomitant with microglial proliferation, astrocytosis, and increased neuropeptide levels in the trigeminal pain system

“…Sensory information traveling from periosteal, meningeal, cutaneous or bony tissues of the head potentially undergoing inflammatory processes after concussion follow the same path and have points of convergence within the trigeminal pathway as that of the vibrissae, which are used by rodents to explore their environment. A connection between the whiskers and the trigeminal pain system has been demonstrated behaviorally in mice [ 52 ]. Convergence of neurons between the potentially inflamed structures and those not injured or inflamed (ie.…”

Understanding the link between obesity and headache- with focus on migraine and idiopathic intracranial hypertension

“…Several animal studies have explored the effects of obesity on migraine-like behaviour in mice, where photophobia and nocifensive behaviours have been assessed. It was demonstrated that both obese female and male mice develop a very modest basal photophobia that was accentuated by facial administration of capsaicin, a TRPV1 agonist and nociceptive [98,99]. The degree of photophobia was weight dependent in high fat diet males, but not in female mice [98,99].…”

“…It was demonstrated that both obese female and male mice develop a very modest basal photophobia that was accentuated by facial administration of capsaicin, a TRPV1 agonist and nociceptive [98,99]. The degree of photophobia was weight dependent in high fat diet males, but not in female mice [98,99]. This photophobic phenotype is replicated in genetically obese ob/ob mice on a normal diet, whereas lean mice on a high fat diet did not exhibit this behaviour, suggesting that excess adiposity confers a photophobic phenotype rather than a high fat diet [98].…”

Body composition status and the risk of migraine

“…32 Further, recent animal data have demonstrated that obesity is associated with both an augmented basal and acute trigeminovascular response to stimulation and may be capable of priming the trigeminovascular system to be responsive to otherwise innocuous stimuli. 38,39 Finally, it is also possible other factors such as changes in physical activity, medications, the presence of comorbidities (e.g., depression), or other medical conditions contribute to the relationship between migraine and obesity and underweight status.…”