Experimental Brain Research

, Volume 236, Issue 2, pp 587–598 | Cite as

Acid-induced experimental knee pain and hyperalgesia in healthy humans

  • T. Asaki
  • Kelun Wang
  • Y. Luo
  • T. Arendt-Nielsen
  • T. Graven-Nielsen
  • L. Arendt-Nielsen
Research Article


Inflammation and the related acidity in peri-articular structures may be involved in pain generation and hyperalgesia in knee osteoarthritis. This study investigated pain and associated hyperalgesia provoked by infusion of acidic saline into the infrapatellar fat pad. Twenty-eight subjects participated in two sessions in which acidic saline (AS, pH 5) or neutral saline (NS, pH 7.4) were infused into the infrapatellar fat pad for 15 min. Pain intensity, pain area, mechanical and thermal sensitivity, and maximal voluntary knee extension force were recorded. Repeated infusions were performed in 14 subjects. Infusion of AS caused significantly higher pain intensity, larger pain areas, induced hyperalgesia around the infused knee, and reduced extension force. No significant pain facilitation or spreading of hyperalgesia was found after repeated infusions as compared with single infusions. Acidic saline infused into the infrapatellar fat pad provoked pain and localized mechanical hyperalgesia. Thus, this acid-induced pain model may mimic the early-stage responses to tissue injury of knee osteoarthritis.


Acid-induced pain Hyperalgesia Osteoarthritis Experimental pain Gender difference 



This study was funded by The Danish Rheumatism Association, The Danish National Advanced Technology Foundation, Aase and Ejnar Danielsen’s Foundation, Lions Club Denmark, and The Danish Council for Technology and Innovation (09-052174). The authors thank professor Brian Edwin Cairns for proofreading the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • T. Asaki
    • 1
  • Kelun Wang
    • 1
  • Y. Luo
    • 1
  • T. Arendt-Nielsen
    • 1
  • T. Graven-Nielsen
    • 1
  • L. Arendt-Nielsen
    • 1
  1. 1.SMI, Department of Health Science and Technology, Faculty of MedicineAalborg UniversityAalborgDenmark

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