Brain Structure and Function

, Volume 224, Issue 3, pp 1119–1139 | Cite as

Brain resting-state connectivity in the development of secondary hyperalgesia in healthy men

  • Morten Sejer HansenEmail author
  • Lino Becerra
  • Jørgen Berg Dahl
  • David Borsook
  • Johan Mårtensson
  • Anders Christensen
  • Janus Damm Nybing
  • Inger Havsteen
  • Mikael Boesen
  • Mohammad Sohail Asghar
Original Article


Central sensitization is a condition in which there is an abnormal responsiveness to nociceptive stimuli. As such, the process may contribute to the development and maintenance of pain. Factors influencing the propensity for development of central sensitization have been a subject of intense debate and remain elusive. Injury-induced secondary hyperalgesia can be elicited by experimental pain models in humans, and is believed to be a result of central sensitization. Secondary hyperalgesia may thus reflect the individual level of central sensitization. The objective of this study was to investigate possible associations between increasing size of secondary hyperalgesia area and brain connectivity in known resting-state networks. We recruited 121 healthy participants (male, age 22, SD 3.35) who underwent resting-state functional magnetic resonance imaging. Prior to the scan session, areas of secondary hyperalgesia following brief thermal sensitization (3 min. 45 °C heat stimulation) were evaluated in all participants. 115 participants were included in the final analysis. We found a positive correlation (increasing connectivity) with increasing area of secondary hyperalgesia in the sensorimotor- and default mode networks. We also observed a negative correlation (decreasing connectivity) with increasing secondary hyperalgesia area in the sensorimotor-, fronto-parietal-, and default mode networks. Our findings indicate that increasing area of secondary hyperalgesia is associated with increasing and decreasing connectivity in multiple networks, suggesting that differences in the propensity for central sensitization, assessed as secondary hyperalgesia areas, may be expressed as differences in the resting-state central neuronal activity.


Pain Secondary hyperalgesia Central sensitization Resting-state fMRI MRI 



We wish to thank the staff of the Department of Radiology, Bispebjerg and Frederiksberg Hospitals for support in obtaining the MRI scans.

Author contributions

All authors contributed in the conception and design of the study, and critically revised the manuscript. All authors read and approved the final manuscript.


This work is supported by grants from the Augustinus foundation (Grant number: 14-3907), Toyota Fonden—Denmark (Grant number: OH/BG-8610), the Aase and Ejnar Danielsen’s foundation (Grant number: 10-001341), and the DASAIM pain research award. Dr. Borsook received funding from NIH Grant NINDS K24 NS064050. The funders had no role in the conception or design of the study, or on the decision to publish the results.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Supplementary material

429_2018_1819_MOESM1_ESM.docx (12 kb)
Supplementary material 1 (DOCX 12 KB)
429_2018_1819_MOESM2_ESM.docx (15 kb)
Supplementary material 2 (DOCX 14 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Morten Sejer Hansen
    • 1
    • 2
    Email author
  • Lino Becerra
    • 3
  • Jørgen Berg Dahl
    • 4
  • David Borsook
    • 5
    • 6
    • 7
  • Johan Mårtensson
    • 8
  • Anders Christensen
    • 2
  • Janus Damm Nybing
    • 2
  • Inger Havsteen
    • 2
  • Mikael Boesen
    • 9
  • Mohammad Sohail Asghar
    • 10
  1. 1.Department of Anaesthesiology, 4231, Centre of Head and OrthopaedicsRigshospitaletCopenhagenDenmark
  2. 2.Department of RadiologyCopenhagen University Hospital Bispebjerg and FrederiksbergCopenhagenDenmark
  3. 3.Invicro, A Konica Minolta CompanyBostonUSA
  4. 4.Department of AnaesthesiologyCopenhagen University Hospital Bispebjerg and FrederiksbergCopenhagenDenmark
  5. 5.Department of Radiology, Athinoula A. Martinos Center for Biomedical ImagingMassachusetts General HospitalCharlestownUSA
  6. 6.Department of Psychiatry, McLean HospitalHarvard Medical SchoolBostonUSA
  7. 7.Department of Psychiatry, Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  8. 8.Department of Clinical Sciences, Faculty of MedicineLund UniversityLundSweden
  9. 9.Department of Radiology and the Parker InstituteCopenhagen University Hospital Bispebjerg and Frederiksberg, Bispebjerg HospitalCopenhagenDenmark
  10. 10.Department of Neuroanaesthesiology, NeurocentreRigshospitaletCopenhagenDenmark

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