Volume 16 Supplement 1

1st Joint ANIRCEF-SISC Congress

Open Access

O042. Phase-dependent defective functional activity of the default mode network and facilitated temporal processing of nociceptive stimuli in cluster headache

  • Armando Perrotta1Email author,
  • Maria Grazia Anastasio1, 2,
  • Luigi Pavone1,
  • Antonio Ferretti3,
  • Piero Chiacchiaretta3,
  • Giovanni Grillea1,
  • Marcello Bartolo1,
  • Emanuele Siravo1,
  • Gianluca Coppola2,
  • Anna Ambrosini1,
  • Roberto De Icco4,
  • Giorgio Sandrini4 and
  • Francesco Pierelli2
The Journal of Headache and Pain201516(Suppl 1):A90


Published: 28 September 2015

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


In cluster headache (CH) during the active period we described a facilitated temporal summation (TS) of nociceptive signals at spinal level linked to a defective suprapinal control of pain and followed by a normalization of the values during the remission period[1]. TS of sensory neuronal responses to nociceptive stimuli is a form of central plasticity that shifts the sensory information from tactile to nociceptive before transmitting the nociceptive information to brain areas mediating pain sensation. This feature of the sensory system results pivotal in physiological nociception, for discrimination between innocuous and potentially dangerous stimulation, as well as in pathological nociception, for induction and maintenance of the central sensitization, subsequently resulting in pain chronification[2]. In this study we sought to determine which brain sites are involved in the modulation of temporal processing of pain sensation in CH subjects during both the active and remission period. We utilized functional magnetic resonance imaging (fMRI) to compare the Blood Oxygenation Level Dependent (BOLD) signal changes related to the temporal summation threshold (TST) of the nociceptive withdrawal reflex (NWR). We used the single NWR response as control stimulus.


We studied 10 episodic CH patients during both active and remission period and 17 healthy subjects (HS). Two types of stimulation blocks were delivered during the fMRI scanning according to the stimulation paradigms previously determined to evoke both the TST of the NWR (SUMM) and the NWR single response (SING).


The analysis of the hemodynamic signals showed a comparable activation of sensory and pain related areas in both CH (during active and remission period) and HS. The most relevant differences emerged in the deactivation of both posterior cingulate cortex (PCC) and bilateral angular gyrus (AG) and in the activation of the anterior cingulate cortex (ACC). CH during the active phase showed a lack of deactivation of PCC and AG and a more relevant activation of the ACC when compared to CH during the remission phase and HS.


PCC, AG and ACC are considered to be pivotal in default mode network (DMN), with a high activity correlated to the rest and reactive deactivation during most tasks where the attention is directed externally. Our data have demonstrated that in CH during the active phase of the disease, the facilitation in temporal processing of nociceptive stimuli is linked to a defective functioning of the DMN. Interestingly, both these abnormalities are dependent on the clinical activity of the disease.

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


Authors’ Affiliations

IRCCS INM Neuromed
Department of Medical and Surgical Sciences and Biotechnologies, “Sapienza” University of Rome Polo Pontino
Department of Neuroscience, Imaging and Clinical Sciences, University “G. d'Annunzio”, Institute for Advanced Biomedical Technologies (ITAB)
IRCCS Neurological National Institute C. Mondino


  1. Perrotta A, Serrao M, Ambrosini A, Bolla M, Coppola G, Sandrini G, Pierelli F: Facilitated temporal processing of pain and defective supraspinal control of pain in cluster headache. Pain. 2013, 154 (8): 1325-32. 10.1016/j.pain.2013.04.012.View ArticlePubMedGoogle Scholar
  2. Perrotta A, Serrao M, Sandrini G, Burstein R, Sances G, Rossi P, Bartolo M, Pierelli F, Nappi G: Sensitisation of spinal cord pain processing in medication overuse headache involves supraspinal pain control. Cephalalgia. 2010, 30 (3): 272-84.PubMedGoogle Scholar


© Perrotta 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 (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.