Similarly, Lu et al

Similarly, Lu et al. nociceptor activity by sex hormones at the transcriptional, translational, and functional levels. Data are being accumulated on the effect of sex hormones on TRP channels such as TRPV1 that make pivotal contributions to nociceptor excitability and sensitization in migraine and other chronic pain syndromes. These data suggest that modulation of TRP channels’ expression and/or activity by gonadal hormones provide novel pathways for drug intervention that may be useful for targeting the sex dimorphism observed in migraine. or modulators of headache attacks through regulation of thermoTRP channels. Although both have separately been proposed as therapeutic targets for migraine intervention, the interrelation of sex hormones and thermoTRPs in the etiology of the disease has not been resolved in depth. Here, we review the role of sex hormones in the activation, modulation, and regulation of the main thermoTRP channels involved in the pathophysiology of migraine. Nonetheless, we should mention that sex differences in migraine, and other chronic pain syndromes, will also be influenced by gonadal-independent X-linked gene expression that contributes to inborn sex differences in organs, tissues, and cells (immune, endothelial, and neurons), as well as by other factors (i.e., psychological and interpersonal) (review in Mogil, 2012; Bartley and Fillingim, 2013). The available information on the influence of these gonadal-independent factors around the pathophysiology of migraine, especially around the expression and activity of TRP channels, is very scarce, thus preventing us from properly addressing it in this evaluate. Accordingly, we focus on Helioxanthin 8-1 the information regarding the direct conversation and modulation of thermoTRP channels by sex hormones, which may, at least in part, underlie the greater prevalence of the disease in women. We suggest that thermoTRPs may symbolize potential therapeutic targets for migraine intervention and other pain syndromes that exhibit sex dimorphism. Influence of sex hormones in migraine Cumulative evidence indicates that migraine is usually a chronic Helioxanthin 8-1 pain disease linked to sex hormones. Firstly, ~15% of the population suffer from this, including children; however, the prevalence in women is usually up to three times higher than in men. Although a peak of incidence appears in individuals in the age range of 25C55 years in both genders, this remains higher in women (Stewart et al., 1992; Lipton et al., 2001, 2007; Mathers et al., 2008; Vetvik and MacGregor, 2017). Second of all, the migraine prevalence changes across the age range. In 2003, a National Health Interview Survey, in which more than 40,000 US-citizens (70% adults and 30% children) were interviewed, showed that boys and girls shared a similar 1-12 months prevalence until puberty, thereafter it increased in both genders, being two or three times greater in women (Victor et al., 2010). This study also found that the largest difference in migraine prevalence occurred at the age of 30.2 years, declining from the age of 42 years (Victor et al., 2010). In women, the prevalence sharply decreased at menopause (Vetvik and MacGregor, 2017). The sex difference in the disease incidence between 15 and 50 years is probably related to the higher level of sex hormones during this age range. Most studies showed a protective role of testosterone and progesterone against migraine crisis, while the data for estrogens were more controversial. You will find studies reporting that low levels of estrogens may be related to an increase in the number of migraine attacks, whereas others suggest that the application of estrogens promotes migraine episodes (observe below). In addition to the higher prevalence of migraine in females, it has also been reported that women experience more frequent, longer-lasting, and more intense attacks than men (Celentano et al., 1990; Boardman et al., 2003). The constant obtaining was that women, in comparison to men, have longer-lasting migraine attacks (Kallela et al., 1999; Steiner et al., 2003; Wober-Bingol et al., 2004; Kelman, 2006; Murtaza et al., 2009; Franconi et al., 2014; Bolay et al., 2015), as well as longer photophobia, phonophobia, nausea, vomiting, and cutaneous allodynia (Steiner et al., 2003; Murtaza et Helioxanthin 8-1 al., 2009; Bolay et al., 2015). One study, which analyzed 2,082 migraine adult patients (1,804 women and 278 men), reported that this headache intensity in FLJ21128 women changed in an age-dependent manner and the period and intensity of.