In cluster headache (CH), pathogenesis has been emphasized the role of the posterior hypothalamus. It is part of a supraspinal network involved in the descending control of pain, including the diffuse noxious inhibitory control (DNIC), which in turn modulates the pain processing. We hypothesized that CH during the active phase facilitated temporal pain processing supported by abnormal functioning of the DNIC. We studied the functional activity of the DNIC by evaluating the effect of the cold pressor test (CPT) on the temporal summation threshold (TST) of the nociceptive withdrawal reflex. Ten subjects with episodic CH (2 women, 8 men) and 10 healthy subjects were recruited. Each subject underwent neurophysiological evaluation (nociceptive withdrawal reflex TST and related painful sensation) at baseline, then before (control session), during (pain session), and 5 min after (aftereffect) the CPT (immersing hand in a 4 degrees C water bath for 4-5 min). Patients had been studied during both the active and remission phases. During the active phase, CH revealed a significant facilitation in temporal processing of pain stimuli (reduction of TST), which reverted during the remission phase. The CPT activating the DNIC did not produce any significant inhibitory effect of pain responses in CH during the active phase, whereas it induced a clear inhibition during the remission phase. We hypothesized that in CH, a dysfunction of the supraspinal control of pain related to the clinical activity of the disease, possibly supported by an abnormal hypothalamic function, leads to a facilitation in pain processing and a predisposition to pain attacks. (C) 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.