Measures of altered hormone are reported in chronic migraine patients (including prolactin, cortisol, and melatonin), which is indicative of abnormalities

in circadian biology (Peres et al., 2001). Thus, the hypothalamus may control systems that could have many functional implications through such alterations in hormone and autonomic function, impinging on many organ systems, including the brain. One example is that of the association of obesity and migraine (Peterlin et al., 2010). Alterations in hypothalamic control Selleckchem Y 27632 may be manifest and contribute to both syndromes, because alterations in neurotransmitters and hypothalamic peptides may be abnormal in both conditions. Given that there may be multiple stressors that contribute to the allostatic load (Figure 4) and increased disease burden with chronification selleck products (Figure 5), ideally, one could evaluate and quantify each and provide a rational approach to devolving, uncoupling, diminishing direct inputs onto systems that modulate the allostatic load and directly impact those systems that have been altered. A new approach to defining and measuring the relative contributions

and their cumulative or additive effects would bring opportunities to improve diseases such as migraine where we only have a limited response in terms of preventing the attacks and/or treating chronic migraine. Specifically, the following principles would seem to be salient: (1) intervene as early as possible to prevent the negative cascade; (2) top-down interventions (e.g., exercise, social support, stress reduction, diet, etc. [see McEwen and Gianaros, 2011]) to help reestablish systemic and brain “balance,”

which may include plastic changes and neuronal connectivity (Castrén, 2005); (3) pharmacotherapy may contribute to the top-down process and may be more efficacious in the context of other modulators of allostasis. One example in support of interactive others effects is the use of antidepressants in the context of a positive therapeutic environment and the notion that multiple therapies may be more beneficial than a single treatment (March et al., 2004). Another example in support of our proposal is the efficacy of antidepressants, along with physiotherapy, in recovery of motor function after stroke (Chollet et al., 2011). (4) On the other hand, as noted above, some medications may contribute to the allostatic overload and make the condition worse. Thus, targeting treatments in the context of modification of multiple neurobiological systems would seem like a rational process to implement at a clinical level. Specific targets include behavioral targets (including sleep and stress modification), but also those directed at brain systems, as noted below.