The hypothalamus: specific or nonspecific role in the pathophysiology of trigeminal autonomic cephalalgias?

The clinical features of trigeminal autonomic cephalalgias (TACs), such as trigeminal distribution of pain, circadian/circannual rhythmicity, and ipsilateral cranial autonomic features, suggest a crucial role of the hypothalamus in the underlying pathophysiology of these primary headache disorders. Hypothalamic involvement is supported by several neuroimaging, neuroendocrine, genetic, experimental pain, and animal studies. Unfortunately, these different studies were unable to resolve the paramount question of whether the detected hypothalamic alterations are pathognomonic for TACs or whether they merely represent an epiphenomenon of different pain conditions in general. This review summarizes studies on hypothalamic involvement in TAC pathophysiology, demonstrates hypothalamic activation in other painful diseases, and evaluates the role of the hypothalamus in the pathophysiologic mechanisms associated with these different conditions.