title: Temporal summation of the nociceptive withdrawal reflex involves deactivation of posterior cingulate cortex.
abstract: Temporal summation of pain sensation is pivotal both in physiological and pathological nociception. In humans, it develops in parallel with temporal summation of the nociceptive withdrawal reflex (NWR) of the lower limb, an objective representation of the temporal processing of nociceptive signals into the spinal cord.
  
  
  
  To study the contribution of cortical and subcortical structures in temporal summation of pain reflex responses, we compared the fMRI signal changes related to the temporal summation threshold (TST) of the NWR with that related to the single NWR response. We studied 17 healthy subjects using a stimulation paradigm previously determined to evoke both the TST of the NWR (SUMM) and the NWR single response (SING).
  
  
  
  We found a significant activation in left (contralateral) primary somatosensory cortex (SI), bilateral secondary somatosensory cortex (SII), bilateral insula, anterior cingulate cortex (ACC) and bilateral thalamus during both SUMM and SING conditions. The SUMM versus SING contrast revealed a significant deactivation in the posterior cingulate cortex (PCC) and bilateral middle occipital gyrus in SUMM when compared to SING condition.
  
  
  
  Our data support the hypothesis that temporal summation of nociceptive reflex responses is driven through a switch between activation and deactivation of a specific set of brain areas linked to the default mode network. This behaviour could be explained in view of the relevance of the pain processing induced by temporal summation, recognized as a more significant potential damaging condition with respect to a single, isolated, painful stimulation of comparable pain intensity.
  
  
  
  The study demonstrated that TST of the NWR involves a selective deactivation of PCC.
authors.affiliation: IRCCS Neuromed, Pozzilli (Isernia), Italy.
authors.forename: A
authors.initials: A
authors.lastname: Perrotta
authors.affiliation: Department of Neuroscience, Imaging and Clinical Sciences, University "G. d'Annunzio" of Chieti, Italy.|Institute for Advanced Biomedical Technologies (ITAB), University "G. d'Annunzio" of Chieti, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Chiacchiaretta
authors.affiliation: IRCCS Neuromed, Pozzilli (Isernia), Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Anastasio
authors.affiliation: IRCCS Neuromed, Pozzilli (Isernia), Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pavone
authors.affiliation: IRCCS Neuromed, Pozzilli (Isernia), Italy.|Department of Neurology and Psychiatry, "Sapienza" University of Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Grillea
authors.affiliation: IRCCS Neuromed, Pozzilli (Isernia), Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bartolo
authors.affiliation: IRCCS Neuromed, Pozzilli (Isernia), Italy.
authors.forename: E
authors.initials: E
authors.lastname: Siravo
authors.affiliation: IRCCS Neuromed, Pozzilli (Isernia), Italy.|Department of Neurology and Psychiatry, "Sapienza" University of Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Colonnese
authors.affiliation: C. Mondino National Neurological Institute, Department of Brain and Behavioral Sciences, University of Pavia, Italy.
authors.forename: R
authors.initials: R
authors.lastname: De Icco
authors.affiliation: Unit of Neurorehabilitation, Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, ICOT, Latina, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Serrao
authors.affiliation: C. Mondino National Neurological Institute, Department of Brain and Behavioral Sciences, University of Pavia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Sandrini
authors.affiliation: IRCCS Neuromed, Pozzilli (Isernia), Italy.|Unit of Neurorehabilitation, Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, ICOT, Latina, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Pierelli
authors.affiliation: Department of Neuroscience, Imaging and Clinical Sciences, University "G. d'Annunzio" of Chieti, Italy.|Institute for Advanced Biomedical Technologies (ITAB), University "G. d'Annunzio" of Chieti, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ferretti
mesh_terms: D000328:Adult; D005260:Female; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D059225:Nociception / Q000502:physiology*; D010146:Pain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D010147:Pain Measurement; D012018:Reflex / Q000502:physiology*; D055815:Young Adult