Cluster headache attacks are characterized by extreme unilateral pain mostly in the first trigeminal branch and an ipsilateral activation of the cranial parasympathetic system, pointing to a relevant role of the cranial parasympathetic system in the pathophysiology, and therapy of cluster headache. Based on animal experiments and several interventions of the sphenopalatine ganglion (such as an aesthetic or alcoholic blocks and radiofrequency ablation) in cluster headache patients, stimulation of the sphenopalatine ganglion (SPGS) as the major efferent peripheral parasympathetic structure was established with an encouraging abortive effect on acute attacks and a frequency reduction over time. In this review, the clinical data and potentially underlying pathophysiological concepts of SPGS are discussed in detail, which in brief point to a relevant role of the parasympathetic system both in the induction and termination of attacks.
