Jump to ContentJump to Main Navigation
Show Summary Details
More options …
New at De Gruyter

Scandinavian Journal of Pain

Official Journal of the Scandinavian Association for the Study of Pain

Editor-in-Chief: Breivik, Harald

4 Issues per year


CiteScore 2017: 0.84

SCImago Journal Rank (SJR) 2017: 0.401
Source Normalized Impact per Paper (SNIP) 2017: 0.452

Online
ISSN
1877-8879
See all formats and pricing
More options …

Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [11C]-D-deprenyl PET/CT

Mikko Aarnio
  • Corresponding author
  • Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, Uppsala University Hospital, Uppsala Sweden
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Lieuwe Appel
  • PET Centre, Department of Medical Imaging, Uppsala University Hospital, Uppsala Sweden
  • Section of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala Sweden
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mats Fredrikson
  • Department of Psychology, Uppsala University, Uppsala Sweden
  • Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Torsten Gordh
  • Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, Uppsala University Hospital, Uppsala Sweden
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Olof Wolf / Jens Sörensen
  • PET Centre, Department of Medical Imaging, Uppsala University Hospital, Uppsala Sweden
  • Section of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala Sweden
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Måns Thulin / Magnus Peterson
  • Department of Public Health and Caring Sciences, Section of Family Medicine and Preventive Medicine, Uppsala University, Uppsala Sweden
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Clas Linnman
  • Department of Anesthesiology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2017-12-29 | DOI: https://doi.org/10.1016/j.sjpain.2017.10.008

Graphical Abstract

Abstract

Background and aims

Positron emission tomography (PET) with the radioligand [11C]-D-deprenyl has shown increased signal at location of pain in patients with rheumatoid arthritis and chronic whiplash injury. The binding site of [11C]-D-deprenyl in peripheral tissues is suggested to be mitochondrial monoamine oxidase in cells engaged in post-traumatic inflammation and tissue repair processes. The association between [11C]-D-deprenyl uptake and the transition from acute to chronic pain remain unknown. Further imaging studies of musculoskeletal pain at the molecular level would benefit from establishing a clinical model in a common and well-defined injury in otherwise healthy and drug-naive subjects. The aim of this study was to investigate if [11C]-D-deprenyl uptake would be acutely elevated in unilateral ankle sprain and if tracer uptake would be reduced as a function of healing, and correlated with pain localizations and pain experience.

Methods

Eight otherwise healthy patients with unilateral ankle sprain were recruited at the emergency department. All underwent [11 C]-D-deprenyl PET/CT in the acute phase, at one month and 6-14 months after injury.

Results

Acute [11C]-D-deprenyl uptake at the injury site was a factor of 10.7 (range 2.9-37.3) higher than the intact ankle. During healing, [11C]-D-deprenyl uptake decreased, but did not normalize until after 11 months. Patients experiencing persistent pain had prolonged [11C]-D-deprenyl uptake in painful locations.

Conclusions and implications

The data provide further support that [11C]-D-deprenyl PET can visualize, quantify and follow processes in peripheral tissue that may relate to soft tissue injuries, inflammation and associated nociceptive signaling. Such an objective correlate would represent a progress in pain research, as well as in clinical pain diagnostics and management.

Keywords: Ankle injuries; Deprenyl; Inflammation; Pain; PET; Carbon-11

References

  • [1]

    Gendreau M, Hufford M, Stone A. Measuring clinical pain in chronic widespread pain: selected methodological issues. Best Pract Res Cli Rheumatol 2003;17:575–92.CrossrefGoogle Scholar

  • [2]

    Basu S, Zhuang H, Torigian D, Rosenbaum J, Chen W, Alavi A. Functional imaging of inflammatory diseases using nuclear medicine techniques. Semin Nucl Med 2009;39:124–45.CrossrefPubMedWeb of ScienceGoogle Scholar

  • [3]

    Gotthardt M, Bleeker-Rovers CP, Boerman OC, Oyen WJ. Imaging of inflammation by PET, conventional scintigraphy, and other imaging techniques. J Nucl Med 2010;51:1937–49.PubMedWeb of ScienceGoogle Scholar

  • [4]

    Ji RR, Chamessian A, Zhang YQ. Pain regulation by non-neuronal cells and inflammation. Science 2016;354:572–7.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [5]

    Lesniak A, Aarnio M, Jonsson A, Norberg T, Nyberg F, Gordh T. High-throughput screening and radioligand binding studies reveal monoamine oxidase-B as the primary binding target for D-deprenyl. Life Sci 2016;152:231–7.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [6]

    Danfors T, Bergstrom M, Feltelius N, Ahlstrom H, Westerberg G, Langstrom B. Positron emission tomography with 11 C-D-deprenyl in patients with rheumatoid arthritis. Evaluation of knee joint inflammation before and after intra-articular glucocorticoid treatment. Scand J Rheumatol 1997;26:43–8.Google Scholar

  • [7]

    Linnman C, Appel L, Fredrikson M, Gordh T, Soderlund A, Langstrom B, Engler H. Elevated [11C]-D-deprenyl uptake in chronic Whiplash Associated Disorder suggests persistent musculoskeletal inflammation. PLoS ONE 2011;6:e19182.CrossrefWeb of SciencePubMedGoogle Scholar

  • [8]

    Fowler JS, MacGregor RR, Wolf AP, Arnett CD, Dewey SL, Schlyer D, Christman D, Logan J, Smith M, Sachs H. Mapping human brain monoamine oxidase A and Bwith 11C-labeled suicide inactivators and PET. Science 1987;235:481–5.CrossrefGoogle Scholar

  • [9]

    Macgregor R, Fowler J, Wolf A, Halldin C, Langstrom B. Synthesis of suicide inhibitors of monoamine oxidase: carbon-11 labeled clorgyline, L-deprenyl and D-deprenyl. J Label Compd Radiopharm 1988;25:1–12.CrossrefGoogle Scholar

  • [10]

    Agresti A. Foundations of linear and generalized linear models. Wiley; 2015. p. 472.Google Scholar

  • [11]

    Nahmias C, Wahl L. Reproducibility of standardized uptake value measurements determined by 18F-FDG PET in malignant tumors. J Nucl Med 2008;49:1804–8.CrossrefPubMedGoogle Scholar

  • [12]

    Krak N, Boellaard R, Hoekstra O, Twisk J, Hoekstra C, Lammertsma A. Effects of ROI definition and reconstruction method on quantitative outcome and applicability in a response monitoring trial. Eur J Nucl Med Mol Imaging 2005;32:294–301.CrossrefGoogle Scholar

  • [13]

    Hamberg L, Hunter G, Alpert N, Choi N, Babich J, Fischman A. The dose uptake ratio as an index of glucose metabolism: useful parameter or over simplification? J Nucl Med 1994;35:1308–12.Google Scholar

  • [14]

    Keyes JJ. SUV: standard uptake or silly useless value? J Nucl Med 1995;36:1836–9.PubMedGoogle Scholar

  • [15]

    Huang S. Anatomy of SUV. Standardized uptake value.Nucl Med Biol 2000;27:643–6.CrossrefGoogle Scholar

  • [16]

    Konradsen L, Bech L, Ehrenbjerg M, Nickelsen T. Seven years follow-up after ankle inversion trauma. Scand J Med Sci Sports 2002;12:129–35.CrossrefPubMedGoogle Scholar

  • [17]

    vanRijn RM, vanOs AG, Bernsen RM, Luijsterburg PA, Koes BW, Bierma-Zeinstra SM. What is the clinical course of acute ankle sprains? A systematic literature review. Am J Med 2008;121, 324-31.e6.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [18]

    Hubbard T, Hicks-Little C. Ankle ligament healing after an acute ankle sprain: an evidence-based approach. JAthl Train 2008;43:523–9.CrossrefGoogle Scholar

  • [19]

    Hintermann B, Boss A, Schafer D. Arthroscopic findings in patients with chronic ankle instability. Am J Sports Med 2002;30:402–9.CrossrefPubMedGoogle Scholar

  • [20]

    Hirose K, Murakami G, Minowa T, Kura H, Yamashita T. Lateral ligament injury of the ankle and associated articular cartilage degeneration in the talocrural joint: anatomic study using elderly cadavers. J Orthop Sci 2004;9:37–43.CrossrefPubMedGoogle Scholar

  • [21]

    Fleming B, Hulstyn M, Oksendahl H, Fadale P. Ligament injury, reconstruction and osteoarthritis. CurrOpin Orthop 2005;16:354–62.Google Scholar

  • [22]

    Clay FJ, Watson WL, Newstead SV, McClure RJ. A systematic review of early prognostic factors for persisting pain following acute orthopedic trauma. Pain Res Manag 2012;17:35–44.PubMedCrossrefGoogle Scholar

  • [23]

    Anna L, Mikko A, Shanti D, Thomas N, Fred N, Torsten G. Characterization of the binding site for D-deprenyl in synovial membranes from arthritic patients; 2017. Unpublished work.Google Scholar

  • [24]

    Balsa MD, Gomez N, Unzeta M. Characterization of monoamine oxidase activity present in human granulocytes and lymphocytes. Biochim Biophys Acta 1989;992:140–4.CrossrefPubMedGoogle Scholar

  • [25]

    Cathcart MK, Bhattacharjee A. Monoamine oxidase A (MAO-A): a signature marker of alternatively activated monocytes/macrophages. Inflamm Cell Signal 2014;1.Google Scholar

  • [26]

    Magyar K, Vizi E, Ecseri Z, Knoll J. Comparative pharmacological analysis of the optical isomers of phenyl-isopropyl-methyl-propinylamine (E-250). Acta Physiol Acad Sci Hung 1967;32:377–87.PubMedGoogle Scholar

  • [27]

    Knoll J, Magyar K. Some puzzling pharmacological effects of monoamine oxidase inhibitors. Adv Biochem Psychopharmacol 1972;5:393–408.PubMedGoogle Scholar

  • [28]

    Robinson JB. Stereoselectivity and isoenzyme selectivity of monoamine oxidase inhibitors. Enantiomers of amphetamine, N-methylamphetamine and deprenyl.Biochem Pharmacol 1985;34:4105–8.CrossrefPubMedGoogle Scholar

About the article

Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, Uppsala University Hospital, ing 70 1 tr, 75185 Uppsala, Sweden


Received: 2017-10-05

Revised: 2017-10-09

Accepted: 2017-10-10

Published Online: 2017-12-29


Ethical issuesThe study was approved by the Ethics Committee of the Faculty of Medicine at Uppsala University, Sweden, and by the Radiation Ethics and Safety Committee of Uppsala University Hospital, Uppsala, Sweden. 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. Informed consent was obtained from all individual participants included in the study.

Conflicts of interestAll authors declare that they have no conflicts of interest.


Citation Information: Scandinavian Journal of Pain, Volume 17, Issue 1, Pages 418–424, ISSN (Online) 1877-8879, ISSN (Print) 1877-8860, DOI: https://doi.org/10.1016/j.sjpain.2017.10.008.

Export Citation

© 2017 Scandinavian Association for the Study of Pain.Get Permission

Comments (0)

Please log in or register to comment.
Log in