Trait- and Frequency-Dependent Dysfunctional Habituation to Trigeminal Nociceptive Stimulation in Trigeminal Autonomic Cephalalgias

We investigated whether the stimulation frequency, the pain phases and different diagnoses of trigeminal autonomic cephalalgias (TACs) may influence the habituation to pain. We studied the habituation of the nociceptive blink reflex (nBR) R2 responses at different stimulation frequencies (SF, 0.05, 0.1, 0.2, 0.3, 0.5, 1Hz), in 28 episodic cluster headache (ECH), 16 during (ECH-in) and 12 outside (ECH-out) the bout; they were compared with 16 episodic paroxysmal hemicrania (EPH) during the bout and 21 healthy subjects (HS). We delivered 26 electrical stimuli and subdivided stimuli 2-26 in five blocks of five responses for each SF. Habituation values for each SF were expressed as the percentages of the mean area value of 2nd-5th block respect to the first one. A significant lower mean percentage decrease of the R2 area across all blocks was found at 0.2-1 Hz SF in ECH-in, ECH-out and EPH when compared to HS. We demonstrated a common frequency-dependent deficit of habituation of trigeminal nociceptive responses at higher SF in ECH and EPH patients, independently from the disease phase. This abnormal temporal pattern of pain processing may suggest a trait-dependent dysfunction of some underlying pain-related subcortical structures, rather than a state-dependent functional abnormality due to the recurrence of the headache attacks during the active period. PERSPECTIVE: Trigeminal autonomic cephalagias showed a frequency-related defective habituation of nociceptive trigeminal responses at the higher stimulation frequencies, irrespectively of the diagnosis and/or the disease phase. We demonstrated that the clinical similarities in the different subtypes of TACs are in parallel with a trait-dependent dysfunction in pain processing.