Several hypothalamic nuclei are involved in regulating energy balance. This regulation occurs through a complex pathway via afferent signals from the periphery to the hypothalamus. These signals are dependent on nutrient status as well as via efferent pathways from the sympathetic and parasympathetic systems.
12,15 While the sympathetic system promotes energy expenditure and decreases feeding, the parasympathetic system promotes energy storage and increases feeding.
In addition, feedback regulation of the central and peripheral signals are involved in achieving feeding and energy balance. For example, signals from adiponectin and leptin act on the arcuate nucleus to produce reciprocal activation or inhibition of the proopiomelanocortin and cocaine- and amphetamine-regulated transcript neurons while also inhibiting or activating the neuropeptide Y and agouti-related peptide neurons.
16,17
Proopiomelanocortin activation from peripheral signals triggers the release of α-melanocyte–stimulating hormone (α-MSH) from axon terminals. Alpha-MSH activates the melanocortin 4 receptor, resulting in suppression of food intake. Signals from the arcuate nucleus neurons are subsequently transmitted to several other hypothalamic nuclei (eg, paraventricular nucleus and lateral hypothalamus), which also play a role in energy regulation.
12,17
In the lateral hypothalamus, two groups of neurons participate in the regulation of feeding: the orexin and melanin-concentrating hormone neurons. The orexin neurons stimulate feeding while the melanin-concentrating hormone neurons inhibit food intake. Neurons project from these hypothalamic neurons to brainstem nuclei (ie, solitary nucleus and tract, dorsomotor nucleus of the vagus nerve) where the descending hypothalamic inputs are integrated with peripheral inputs from the liver and gastrointestinal tract.
12,15,18
Hypothalamic involvement in several headache disorders has been well described (eg, migraine, cluster headache, and other trigeminal autonomic cephalalgia).
13,19,20 The hypothalamic role in migraine was first suggested based on the clinical observations of premonitory symptoms in migraineurs: changes in alertness, thirst, food cravings, and mood or sleep disturbances.
19 More recently, functional imaging data using positron emission tomography supported these clinical observations, with hypothalamic activation being demonstrated during acute migraine attacks.
13 Thus, it is possible that the hypothalamic peptides activated in feeding are also activated in migraine.