The Journal of Headache and Pain

Official Journal of the "European Headache Federation" and of "Lifting The Burden - The Global Campaign against Headache"

The Journal of Headache and Pain Cover Image

Volume 16 Supplement 1

1st Joint ANIRCEF-SISC Congress

Open Access

O044. Frequency-dependent habituation deficit of the nociceptive blink reflex in migraine with and without aura

  • Maria Grazia Anastasio1, 2Email author,
  • Armando Perrotta1,
  • Gianluca Coppola2,
  • Anna Ambrosini1,
  • Giorgio Sandrini3,
  • Roberto De Icco3 and
  • Francesco Pierelli2
The Journal of Headache and Pain201516(Suppl 1):A59

Published: 28 September 2015

The Erratum to this article has been published in The Journal of Headache and Pain 2017 18:11


MigraineStimulation FrequencyMigraine Without AuraAbnormal ProcessingConsecutive Block


The habituation phenomenon is a frequency-dependent form of non-associative learning which reflects the excitability level of both sensory and pain systems. We previously demonstrated a frequency-dependent deficit of habituation of the conventional blink reflex in migraine[1]. We investigated the habituation of the trigeminal nociceptive system by studying the habituation of the late component (R2) of the nociceptive blink reflex (nBR) in a wide range of stimulation frequencies in subjects with migraine without aura (MWoA) and with aura (MWA).


We studied, interictally, 25 MWoA and 17 MWA subjects, as well as 20 healthy control subjects. We delivered a series of 26 electrical stimuli, at different and randomly chosen stimulation frequencies (0.05, 0.1, 0.2, 0.3, 0.5, and 1Hz), subsequently subdivided into five consecutive blocks of five averaged and rectified responses for each stimulation frequency. Habituation was measured as the percentage decrease of the mean area under the curve of the R2 component across the blocks.


A significant habituation deficit in the R2 component of the nBR was diffusely found at higher (1Hz and 0.5Hz) and intermediate (0.3 and 0.2Hz) frequencies in MWoA when compared to controls. MWA showed a significant habituation deficit at intermediate (0.3 and 0.2Hz) frequencies when compared to controls. No differences in habituation rate were found at lower (0.1 and 0.05Hz) frequencies between patients and controls.


A frequency-dependent habituation deficit in trigeminal nociception was clearly detected in MWoA at higher and intermediate frequencies. It indicates a wide abnormal processing of painful stimuli at the trigeminal level during the interictal period. On the contrary, MWA showed a clear habituation deficit at intermediate (0.3 and 0.2Hz) frequencies, only revealing a less impaired trigeminal nociceptive excitability during the interictal period. Our data provide further evidence for functional differences between MWoA and MWA.

Written informed consent to publication was obtained from the patient(s).


Authors’ Affiliations

Headache Clinic, IRCCS INM Neuromed, Pozzilli, Italy
Department of Medical and Surgical Sciences and Biotechnologies, “Sapienza" University of Rome Polo Pontino, Rome, Italy
IRCCS Neurological National Institute C. Mondino, Pavia, Italy


  1. Perrotta A, Serrao M, Sandrini G, Bogdanova D, Tassorelli C, Bartolo M, Coppola G, Pierelli F, Nappi G: Reduced habituation of trigeminal reflexes in patients with episodic cluster headache during cluster period. Cephalalgia. 2008, 28 (9): 950-9. 10.1111/j.1468-2982.2008.01631.x.View ArticlePubMedGoogle Scholar


© Anastasio et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.