Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Scandinavian Journal of Pain

Official Journal of the Scandinavian Association for the Study of Pain

Editor-in-Chief: Breivik, Harald


CiteScore 2018: 0.85

SCImago Journal Rank (SJR) 2018: 0.494
Source Normalized Impact per Paper (SNIP) 2018: 0.427

Online
ISSN
1877-8879
See all formats and pricing
More options …
Volume 19, Issue 1

Issues

Exercise-induce hyperalgesia, complement system and elastase activation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – a secondary analysis of experimental comparative studies

Andrea Polli
  • Corresponding author
  • Pain in Motion Research Group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussels, Laarbeeklaan 103, 1090 Jette, Brussels, Belgium, Phone/Fax: +32 (0) 2 477 45 29
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jessica Van Oosterwijck
  • Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
  • Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mira Meeus
  • Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
  • Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, Ghent University, Antwerp, Belgium
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Luc Lambrecht / Jo Nijs
  • Pain in Motion Research Group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussels, Laarbeeklaan 103, 1090 Jette, Brussels, Belgium
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Kelly Ickmans
  • Pain in Motion Research Group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussels, Laarbeeklaan 103, 1090 Jette, Brussels, Belgium
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2018-10-16 | DOI: https://doi.org/10.1515/sjpain-2018-0075

Abstract

Background and aims

The interaction between the immune system and pain has been thoroughly explored in the recent decades. The release of inflammatory mediators from immune cells has the capability of activating neurons and glial cells, in turn sensitizing the nervous system. Both immune system alterations and pain modulation dysfunctions have been shown in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) following exercise. However, no studies tried to explore whether these two phenomena are linked and can explain exercise-induced symptoms worsening in people with ME/CFS. We hypothesized that exercise-induced changes in descending pain modulation is associated to changes in immune system functions. We used complement system product C4a and elastase activity as indicators of immune system activity.

Methods

The study design was a secondary analysis of controlled experimental studies. Twenty-two patients with ME/CFS and 22 healthy sedentary controls were enrolled. In experiment 1, subjects performed an aerobic submaximal exercise test; in experiment 2 they underwent a self-paced exercise test. One week of rest period were set between the two exercise tests. Before and after each experiment, subjects underwent clinical assessment, pain thresholds (PPTs) measurement, and blood sampling. Immune system function was assessed measuring complement system C4a products and elastase activity.

Results

Changes in elastase activity were not associated to changes in PPTs. Associations were observed in the ME/CFS group between changes in PPTs and C4a products, following both types of exercise. After submaximal exercise, the change in C4a products was associated with the change in PPT at the thumb in patients (r=0.669, p=0.001). Similarly, after self-paced exercise the change in C4a products was associated witht the change in PPT at the calf in patients (r=0.429, p=0.047). No such correlations were found in healthy controls. Regression analysis showed that C4a changes after the submaximal exercise significantly predicted the change in PPTs (R2=0.236; p=0.02).

Conclusions

Moderate associations between exercise-induced changes in PPTs and immune system activity were found only in ME/CFS. The change in the complement system following submaximal exercise might be able to explain part of the change in patient’s pain thresholds, providing evidence for a potential link between immune system alteration and dysfunctional endogenous pain modulation. These results have to be taken with caution, as only one out of three measures of PPTs was found associated with C4a changes. We cannot reject the hypothesis that C4a might therefore be a confounding factor, and changes during exercise might be mediated by other mechanism.

Implications

Immune system changes following exercise might contribute to exercise-induced symptoms worsening in patients with ME/CFS. However, the role of the complement system is questionable.

Keywords: pain; immune system; exercise; chronic fatigue syndrome; pain threshold; hyperalgesia

References

  • [1]

    Marchand F, Perretti M, McMahon SB. Role of the immune system in chronic pain. Nat Rev Neurosci 2005;6:521–32.CrossrefPubMedGoogle Scholar

  • [2]

    McMahon SB, La RF, Bennett DLH. Crosstalk between the nociceptive and immune systems in host defence and disease. Nat Rev Neurosci 2015;16:389–402.CrossrefPubMedGoogle Scholar

  • [3]

    Ren K, Dubner R. Interactions between the immune and nervous systems in pain. Nat Med 2010;16:1267–76.PubMedCrossrefGoogle Scholar

  • [4]

    Grace PM, Hutchinson MR, Maier SF, Watkins LR. Pathological pain and the neuroimmune interface. Nat Rev Immunol 2014;3:217–31.Google Scholar

  • [5]

    Bobinski F, Teixeira JM, Sluka KA, Soares Santos AR. IL-4 mediates the analgesia produced by low-intensity exercise in mice with neuropathic pain. Pain 2017;159:437–50.Google Scholar

  • [6]

    Cheng YY, Kao CL, Ma HI, Hung CH, Wang CT, Liu DH, Chen PY, Tsai KL. SIRT1-related inhibition of pro-inflammatory responses and oxidative stress are involved in the mechanism of nonspecific low back pain relief after exercise through modulation of Toll-like receptor 4. J Biochem 2015;158:299–308.CrossrefPubMedGoogle Scholar

  • [7]

    Rajeevan MS, Dimulescu I, Murray J, Falkenberg VR, Unger ER. Pathway-focused genetic evaluation of immune and inflammation related genes with chronic fatigue syndrome. Hum Immunol 2015;76:553–60.CrossrefPubMedGoogle Scholar

  • [8]

    Generaal E, Vogelzangs N, Macfarlane GJ, Geenen R, Smit JH, Dekker J, Penninx BWJH. Basal inflammation and innate immune response in chronic multisite musculoskeletal pain. Pain 2014;155:1605–12.CrossrefPubMedGoogle Scholar

  • [9]

    Bote ME, Garcia JJ, Hinchado MD, Ortega E. Fibromyalgia: anti-inflammatory and stress responses after acute moderate exercise. PLoS One 2013;8:e74524.PubMedCrossrefGoogle Scholar

  • [10]

    Blundell S, Ray KK, Buckland M, White PD. Chronic fatigue syndrome and circulating cytokines: a systematic review. Brain Behav Immun 2015;50:186–95.PubMedCrossrefGoogle Scholar

  • [11]

    Keech A, Vollmer-Conna U, Barry BK, Lloyd AR. Gene expression in response to exercise in patients with chronic fatigue syndrome: a pilot study. Front Physiol 2016;7:421.PubMedGoogle Scholar

  • [12]

    Nijs J, Nees A, Paul L, De Kooning M, Ickmans K, Meeus M, Van Oosterwijck J. Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review. Exerc Immunol Rev 2014;20: 94–116.PubMedGoogle Scholar

  • [13]

    Carroll MC. The complement system in regulation of adaptive immunity. Nat Immunol 2004;5:981–6.CrossrefPubMedGoogle Scholar

  • [14]

    Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol 2010;11:785–97.PubMedCrossrefGoogle Scholar

  • [15]

    Dunkelberger JR, Song W. Complement and its role in innate and adaptive immune responses. Cell Res 2010;20:34–50.PubMedCrossrefGoogle Scholar

  • [16]

    DeLeo JA, Yezierski RP. The role of neuroinflammation and neuroimmune activation in persistent pain. Pain 2001;90:1–6.PubMedCrossrefGoogle Scholar

  • [17]

    Jang JH, Clark JD, Li X, Yorek MS, Usachev YM, Brennan TJ. Nociceptive sensitization by complement C5a and C3a in mouse. Pain 2010;148:343–52.PubMedCrossrefGoogle Scholar

  • [18]

    Zhao P, Lieu TM, Barlow N, Sostegni S, Haerteis S, Korbmacher C, Liedtke W, Jimenez-Vargas NN, Vanner SJ, Bunnett NW. Neutrophil elastase activates protease-activated receptor-2 (PAR2) and transient receptor potential vanilloid 4 (TRPV4) to cause inflammation and pain. J Biol Chem 2015;290:13875–87.PubMedCrossrefGoogle Scholar

  • [19]

    Demettre E, Bastide L, D’Haese A, De Smet K, De Meirleir K, Tiev KP, Englebienne P, Lebleu B. Ribonuclease L proteolysis in peripheral blood mononuclear cells of chronic fatigue syndrome patients. J Biol Chem 2002;277:35746–51.CrossrefPubMedGoogle Scholar

  • [20]

    Nijs J, De Meirleir K, Meeus M, McGregor NR, Englebienne P. Chronic fatigue syndrome: intracellular immune deregulations as a possible etiology for abnormal exercise response. Med Hypotheses 2004;62:759–65.PubMedCrossrefGoogle Scholar

  • [21]

    Skalniak L, Mizgalska D, Zarebski A, Wyrzykowska P, Koj A, Jura J. Regulatory feedback loop between NF-kappaB and MCP-1-induced protein 1 RNase. FEBS J 2009;276:5892–905.CrossrefPubMedGoogle Scholar

  • [22]

    Meffert MK, Chang JM, Wiltgen BJ, Fanselow MS, Baltimore D. NF-kappa B functions in synaptic signaling and behavior. Nat Neurosci 2003;6:1072–8.CrossrefPubMedGoogle Scholar

  • [23]

    Perkins ND. Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 2007;8:49–62.CrossrefPubMedGoogle Scholar

  • [24]

    Döring G. The role of neutrophil elastase in chronic inflammation. Am J Respir Crit Care Med 1994;150(6 Pt 2):S114–7.CrossrefPubMedGoogle Scholar

  • [25]

    Trzybulska D, Olewicz-Gawlik A, Graniczna K, Kisiel K, Moskal M, Cieślak D, Hrycaj P. Quantitative analysis of elastase and cathepsin G mRNA levels in peripheral blood CD14+ cells from patients with rheumatoid arthritis. Cell Immunol 2014;292:40–4.PubMedCrossrefGoogle Scholar

  • [26]

    Aslakson E, Vollmer-Conna U, White PD. An empirical delineation of the heterogeneity of chronic unexplained fatigue in women. Pharmacogenomics 2006;7:355–64.CrossrefPubMedGoogle Scholar

  • [27]

    Van Oosterwijck J, Nijs J, Meeus M, Lefever I, Huybrechts L, Lambrecht L, Paul L. Pain inhibition and postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: an experimental study. J Intern Med 2010;268:265–78.PubMedCrossrefGoogle Scholar

  • [28]

    Naugle KM, Fillingim RB, Riley JL. A meta-analytic review of the hypoalgesic effects of exercise. J Pain 2012;13:1139–50.CrossrefPubMedGoogle Scholar

  • [29]

    Meeus M, Roussel NA, Truijen S, Nijs J. Reduced pressure pain thresholds in response to exercise in chronic fatigue syndrome but not in chronic low back pain: an experimental study. J Rehabil Med 2010;42:884–90.CrossrefPubMedGoogle Scholar

  • [30]

    Meeus M, Hermans L, Ickmans K, Struyf F, Van Cauwenbergh D, Bronckaerts L, De Clerck LS, Moorken G, Hans G, Grosemans S. Endogenous pain modulation in response to exercise in patients with rheumatoid arthritis, patients with chronic fatigue syndrome and comorbid fibromyalgia, and healthy controls: a double-blind randomized controlled trial. Pain Pract 2015;15:98–106.PubMedCrossrefGoogle Scholar

  • [31]

    Lorusso L, Mikhaylova SV, Capelli E, Ferrari D, Ngonga GK, Ricevuti G. Immunological aspects of chronic fatigue syndrome. Autoimmun Rev 2009;8:287–91.PubMedCrossrefGoogle Scholar

  • [32]

    Sorensen B, Jones J, Vernon S. Transcriptional control of complement activation in an exercise model of chronic fatigue syndrome. Molecular 2009;15:34–42.Google Scholar

  • [33]

    Light AR, Bateman L, Jo D, Hughen RW, Vanhaitsma TA, White AT, Light KC. Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome. J Intern Med 2012;271:64–81.CrossrefPubMedGoogle Scholar

  • [34]

    Sorensen B, Streib JE, Strand M, Make B, Giclas PC, Fleshner M, Jones JF. Complement activation in a model of chronic fatigue syndrome. J Allergy Clin Immunol 2003;112:397–403.CrossrefGoogle Scholar

  • [35]

    Nijs J, Van Oosterwijck J, Meeus M, Lambrecht L, Metzger K, Frémont M, Paul L. Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1beta. J Intern Med 2010;267:418–35.PubMedCrossrefGoogle Scholar

  • [36]

    Nijs J, Meeus M, McGregor NR, Meeusen R, De Schutter G, Van Hoof E, De meirleir K. Chronic fatigue syndrome: exercise performance related to immune dysfunction. Med Sci Sport Exerc 2005;37:1647–54.CrossrefGoogle Scholar

  • [37]

    Englebienne P. RNase L in health and disease-what did we learn recently? J Chronic Fatigue Syndr 2003;11:97–109.CrossrefGoogle Scholar

  • [38]

    Vanderweeën L, Oostendorp RAB, Vaes P, Duquet W. Pressure algometry in manual therapy. Man Ther 1996;1:258–65.CrossrefPubMedGoogle Scholar

  • [39]

    Neziri AY, Limacher A, Jüni P, Radanov BP, Andersen OK, Arendt-Nielsen L, Curatolo M. Ranking of tests for pain hypersensitivity according to their discriminative ability in chronic neck pain. Reg Anesth Pain Med 2013;38:308–20.PubMedCrossrefGoogle Scholar

  • [40]

    Cantarero-villanueva I, Rey U, Carlos J. Widespread mechanical pain hypersensitivity as a sign of central sensitization after breast cancer surgery: comparison between mastectomy and lumpectomy. Pain Med 2017;12:72–8.Google Scholar

  • [41]

    Arendt-Nielsen L, Svensson P, Sessle BJ, Cairns BE, Wang K. Interactions between glutamate and capsaicin in inducing muscle pain and sensitization in humans. Eur J Pain 2008;12:661–70.CrossrefPubMedGoogle Scholar

  • [42]

    Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med 1994;121:953–9.CrossrefGoogle Scholar

  • [43]

    Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990;33:160–72.CrossrefPubMedGoogle Scholar

  • [44]

    Mork PJ, Holtermann A, Nilsen TIL. Effect of body mass index and physical exercise on risk of knee and hip osteoarthritis: longitudinal data from the Norwegian HUNT Study. J Epidemiol Community Heal 2012;66:678–83.CrossrefGoogle Scholar

  • [45]

    Stewart AL, Hays RD, Wells KB, Rogers WH, Spritzer KL, Greenfield S. Long-term functioning and well-being outcomes associated with physical activity and exercise in patients with chronic conditions in the medical outcomes study. J Clin Epidemiol 1994;47:719–30.PubMedCrossrefGoogle Scholar

  • [46]

    Wise EA, Price DD, Myers CD, Heft MW, Robinson ME. Gender role expectations of pain: relationship to experimental pain perception. Pain 2002;96:335–42.CrossrefPubMedGoogle Scholar

  • [47]

    Mogil JS, Bailey AL. Sex and gender differences in pain and analgesia. Prog Brain Res 2010;186:141–57.PubMedGoogle Scholar

  • [48]

    Wallman K, Goodman C, Morton A, Grove R, Dawson B. Test-retest reliability of the aerobic power index component of the tri-level fitness profile in a sedentary population. J Sci Med Sport 2003;6:443–54.CrossrefGoogle Scholar

  • [49]

    Wallman K, Goodman C, Morton A, Grove R, Dawson B. Test-retest reliability of the aerobic power index test in patients with chronic fatigue syndrome. J Chronic Fatigue Syndr 2004;11:19–32.Google Scholar

  • [50]

    Telford RD, Minikin BR, Hahn AG, Hooper LA. A simple method for the assessment of general fitness: the tri-level profile. Aust J Sci Med Sport 1989;21:6–9.Google Scholar

  • [51]

    Nijs J, Paul L, Wallman K. Chronic fatigue syndrome: an approach combining self-management with graded exercise to avoid exacerbations. J Rehabil Med 2008;40:241–7.PubMedCrossrefGoogle Scholar

  • [52]

    Denman M, Larun L. Review: exercise therapy reduces fatigue in chronic fatigue syndrome. Ann Intern Med 2016;164:JC55.CrossrefPubMedGoogle Scholar

  • [53]

    Ohashi K, Yamamoto Y, Natelson BH. Activity rhythm degrades after strenuous exercise in chronic fatigue syndrome. Physiol Behav 2002;77:39–44.CrossrefPubMedGoogle Scholar

  • [54]

    Hawk C, Jason LA, Torres-Harding S. Differential diagnosis of chronic fatigue syndrome and major depressive disorder. Int J Behav Med 2006;13:244–51.CrossrefPubMedGoogle Scholar

  • [55]

    Komaroff AL. An examination of the working case definition of chronic fatigue syndrome. Am J Med 1996;100:56–64.CrossrefPubMedGoogle Scholar

  • [56]

    Liszewski MK, Atkinson JP. Complement regulators in human disease: lessons from modern genetics. J Intern Med 2015;277:294–305.PubMedCrossrefGoogle Scholar

  • [57]

    Ting E, Guerrero ATG, Cunha TM, Verri WA, Taylor SM, Woodruff TM, Cunha FQ, Ferreira SH. Role of complement C5a in mechanical inflammatory hypernociception: potential use of C5a receptor antagonists to control inflammatory pain. Br J Pharmacol 2008;153:1043–53.PubMedGoogle Scholar

  • [58]

    Griffin RS, Costigan M, Brenner GJ, Ma CH, Scholz J, Moss A, Allchorne AJ, Stahl GL, Woolf CJ. Complement induction in spinal cord microglia results in anaphylatoxin C5a-mediated pain hypersensitivity. J Neurosci 2007;27:8699–708.CrossrefPubMedGoogle Scholar

  • [59]

    Levin ME, Jin JG, Ji RR, Tong JF, Pomonis JD, Lavery DJ, Miller SW, Chiang LW. Complement activation in the peripheral nervous system following the spinal nerve ligation model of neuropathic pain. Pain 2008;137:182–201.CrossrefPubMedGoogle Scholar

  • [60]

    Scully LJ, Toze C, Sengar DP, Goldstein R. Early-onset autoimmune hepatitis is associated with a C4A gene deletion. Gastroenterology 1993;104:1478–84.CrossrefPubMedGoogle Scholar

  • [61]

    Sjöholm AG, Jönsson G, Braconier JH, Sturfelt G, Truedsson L. Complement deficiency and disease: an update. Mol Immunol 2006;43:78–85.CrossrefPubMedGoogle Scholar

  • [62]

    Arason GJ, Kolka R, Hreidarsson AB, Gudjonsson H, Schneider PM, Fry L, Arnason A. Defective prevention of immune precipitation in autoimmune diseases is independent of C4A*Q0. Clin Exp Immunol 2005;140:572–9.CrossrefPubMedGoogle Scholar

  • [63]

    Rigby WFC, Wu YL, Zan M, Zhou B, Rosengren S, Carlson C, Hilton W, Yu CY. Increased frequency of complement C4B deficiency in rheumatoid arthritis. Arthritis Rheum 2012;64: 1338–44.PubMedCrossrefGoogle Scholar

  • [64]

    Traustadottir KH, Sigfusson A, Steinsson K, Erlendsson K. C4A deficiency and elevated level of immune complexes: the mechanism behind increased susceptibility to systemic lupus erythematosus. J Rheumatol 2002;29: 2359–66.PubMedGoogle Scholar

  • [65]

    Brenu EW, Huth TK, Hardcastle SL, Fuller K, Kaur M, Johnston S, Ramos SB, Staines DR, Marshall-Gradisnik SM. Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis. Int Immunol 2014;26:233–42.CrossrefPubMedGoogle Scholar

  • [66]

    Maes M, Mihaylova I, Kubera M, Leunis JC, Twisk FNM, Geffard M. IgM-mediated autoimmune responses directed against anchorage epitopes are greater in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) than in major depression. Metab Brain Dis 2012;27:415–23.CrossrefPubMedGoogle Scholar

  • [67]

    Loebel M, Grabowski P, Heidecke H, Bauer S, Hanitsch LG, Wittke K, Meisel C, Reinke P, Volk H-D, Fluge Ø, Mella O, Scheibenbogen C. Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome. Brain Behav Immun 2015;52:32–9.PubMedGoogle Scholar

  • [68]

    Chapman CR, Tuckett RP, Song CW. Pain and stress in a systems perspective: reciprocal neural, endocrine, and immune interactions. J Pain 2008;9:122–45.CrossrefGoogle Scholar

  • [69]

    Light AR, White AT, Hughen RW, Light KC. Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects. J Pain 2009;10:1099–112.PubMedCrossrefGoogle Scholar

About the article

aPain in Motion International Research Group, www.paininmotion.be


Received: 2018-04-26

Revised: 2018-08-17

Accepted: 2018-08-20

Published Online: 2018-10-16

Published in Print: 2019-01-28


Authors’ statements

Research funding: The study was funded by ME Research UK, a national charity funding biomedical research into myalgic encephalomyelitis/chronic fatigue syndrome. Jo Nijs is holder of the Chair “Exercise immunology and chronic fatigue in health and disease” funded by the Berekuyl Academy, The Netherlands. Kelly Ickmans is a postdoctoral research fellow of the Agency for Innovation by Science and Technology (IWT) – Applied Biomedical Research Program (TBM), Belgium. Jessica Van Oosterwijck is a Postdoctoral Fellow funded by the Research Foundation – Flanders (FWO). Andrea Polli is a PhD research fellow founded by ME Research UK, for research into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Conflict of interest: Authors declare no conflict of interests.

Informed consent: All subjects were well informed about the aim of the study and the procedures and provided written informed consent before data collection was initiated.

Ethical approval: The Ethics Committee of our University Hospital approved the study protocol.


Citation Information: Scandinavian Journal of Pain, Volume 19, Issue 1, Pages 183–192, ISSN (Online) 1877-8879, ISSN (Print) 1877-8860, DOI: https://doi.org/10.1515/sjpain-2018-0075.

Export Citation

©2018 Scandinavian Association for the Study of Pain. Published by Walter de Gruyter GmbH, Berlin/Boston. All rights reserved.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Anna Gregorowski, Jane Simpson, and Terry Y. Segal
Current Opinion in Pediatrics, 2019, Volume 31, Number 4, Page 462
[2]
Vegard Bruun Bratholm Wyller
Scandinavian Journal of Pain, 2019, Volume 19, Number 1, Page 5

Comments (0)

Please log in or register to comment.
Log in