Migraine and obesity are associated in several ways. First, both are prevalent 
and disabling disorders influenced by genetic and environmental risk factors. 
Second, migraine with aura, as obesity, seems to be a risk factor for 
cardiovascular events. Finally, large population-based studies suggest that 
obesity is a risk factor for chronic migraine after adjusting for comorbidities. 
In this article, we discuss plausible mechanisms that may account for this 
association. Several of the inflammatory mediators that are increased in obese 
individuals are important in migraine pathophysiology, including interleukins 
and calcitonin gene-related peptide (CGRP). These mediators may increase the 
frequency, severity, and duration of migraine attacks per se, which in turn 
would cause central sensitization. Repeated central sensitization may be 
associated with permanent neuronal damage close to the periaqueductal gray area, 
with poor modulation to pain. Obesity is also a state of sympathetic activation, 
which may contribute to increase in headache frequency. Furthermore, the levels 
of adiponectin are decreased in obesity. At low but not normal levels, 
adiponectin is nociceptive. Shared biologic predisposition may also play a major 
role. Orexins modulate both pain and metabolism. Dysfunction in the orexins 
pathways seems to be a risk factor for both conditions. Finally, conditions that 
are comorbid to both states (e.g., depression, sleep apnea) may also make the 
relationship between both diseases more complex.