The association between areas of secondary hyperalgesia and volumes of the caudate nuclei and other pain relevant brain structures—A 3-tesla MRI study of healthy men

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Introduction Central sensitization plays a pivotal role in maintenance of pain and is believed to be intricately involved in several chronic pain conditions. One clinical manifestation of central sensitization is secondary hyperalgesia. The degree of secondary hyperalgesia presumably reflects individual levels of central sensitization. The objective of this study was to investigate the association between areas of secondary hyperalgesia and volumes of the caudate nuclei and other brain structures involved in pain processing. Materials and methods We recruited 121 healthy male participants; 118 were included in the final analysis. All participants underwent whole brain magnetic resonance imaging (MRI). Prior to MRI, all participants underwent pain testing. Secondary hyperalgesia was induced by brief thermal sensitization. Additionally, we recorded heat pain detection thresholds (HPDT), pain during one minute thermal stimulation (p-TS) and results of the Pain Catastrophizing Scale (PCS) and Hospital Anxiety and Depression score (HADS). Results We found no significant associations between the size of the area of secondary hyperalgesia and the volume of the caudate nuclei or of the following structures: primary somatosensory cortex, anterior and mid cingulate cortex, putamen, nucleus accumbens, globus pallidus, insula and the cerebellum. Likewise, we found no significant associations between the volume of the caudate nuclei and HPDTs, p-TS, PCS and HADS. Conclusions Our findings indicate that the size of the secondary hyperalgesia area is not associated with the volume of brain structures relevant for pain processing, suggesting that the propensity to develop central sensitization, assessed as secondary hyperalgesia, is not correlated to brain structure volume.


  • Morten S. Hansen
  • Mohammad S. Asghar
  • Jørn Wetterslev
  • Christian B. Pipper
  • Johan Mårtensson
  • Lino Becerra
  • Anders Christensen
  • Janus D. Nybing
  • Inger Havsteen
  • Mikael Boesen
  • Jørgen B. Dahl
External organisations
  • Copenhagen University Hospital
  • University of Copenhagen
  • Invicro
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology
Original languageEnglish
Article numbere0201642
JournalPLoS ONE
Issue number8
Publication statusPublished - 2018 Aug 1
Publication categoryResearch