Cluster headaches are associated with decreased habituation, the reduction in the perception of a stimulus after repeated exposures, of the nociceptors (pain receptors). The pain is caused by activation of the trigeminal system, which is indicated by higher levels of calcitonin gene related peptide (CGRP) during cluster headache episodes. Cluster headaches often occur in patterns, so the hypothalamus could play a role in activating the trigeminal system, as it is important for our "biological clock."