Skip to main content

Advertisement

Log in

Complex Regional Pain Syndrome Type I: Neuropathic or Not?

  • Published:
Current Pain and Headache Reports Aims and scope Submit manuscript

Abstract

Complex regional pain syndrome (CRPS) is clinically characterized by pain, abnormal regulation of blood flow and sweating, edema of skin and subcutaneous tissues, active and passive movement disorders, and trophic changes. It is classified as type I (reflex sympathetic dystrophy) and type II (causalgia). CRPS cannot be reduced to one system or to one mechanism only. In the past decades, there has been absolutely no doubt that complex regional pain syndromes have to be classified as neuropathic pain disorders. This situation changed when a proposal to redefine neuropathic pain states was recently published, which resulted in an exclusion of CRPS from neuropathic pain disorders. We analyzed the strength of the scientific evidence that supports the neuropathic nature of complex regional pain syndromes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Mitchell S: Injuries of Nerves and their Consequences. Dover: New York, 1865.

    Google Scholar 

  2. Sudeck P: Über die akute (trophoneurotische) Knochenatrophie nach Entzündungen und Traumen der Extremitäten. Deut Med Wschr 1902, 28:336–342.

    Article  Google Scholar 

  3. Evans JA: Reflex sympathetic dystrophy. Surg Clin North Am 1946, 26:435–448.

    Google Scholar 

  4. Sandroni P, Benrud-Larson LM, McClelland RL, Low PA: Complex regional pain syndrome type I: incidence and prevalence in Olmsted county, a population-based study. Pain 2003, 103:199–207.

    Article  PubMed  Google Scholar 

  5. de Mos M, de Bruijn AG, Huygen FJ, et al.: The incidence of complex regional pain syndrome: a population-based study. Pain 2007, 129:12–20.

    Article  PubMed  Google Scholar 

  6. Wasner G, Schattschneider J, Heckmann K, et al.: Vascular abnormalities in reflex sympathetic dystrophy (CRPS I): mechanisms and diagnostic value. Brain 2001, 124(Pt 3):587–599.

    Article  CAS  PubMed  Google Scholar 

  7. • Schattschneider J, Hartung K, Stengel M, et al.: Endothelial dysfunction in cold type complex regional pain syndrome. Neurology 2006, 67:673–675. The authors examined the endothelial function in cold-type chronic CRPS I. The results demonstrate impaired endothelial function in chronic CRPS I.

    Article  CAS  PubMed  Google Scholar 

  8. • Maihöfner C, Baron R, DeCol R, et al.: The motor system shows adaptive changes in complex regional pain syndrome. Brain 2007, 130(Pt 10):2671–2687. The results of this study suggest that substantial adaptive changes within the central nervous system may contribute to motor symptoms in CRPS.

    Article  PubMed  Google Scholar 

  9. van Rijn MA, Marinus J, Putter H, van Hilten JJ: Onset and progression of dystonia in complex regional pain syndrome. Pain 2007, 130:287–293.

    Article  PubMed  Google Scholar 

  10. Merskey H, Bogduk N: Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definition of Terms, edn 2. IASP Press, Seattle; 1994.

    Google Scholar 

  11. •• Treede RD, Jensen TS, Campbell JN, et al.: Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 2008, 70:1630–1635. This article presents a more precise definition of neuropathic pain developed by a group of experts from the neurology and pain fields.

    Article  CAS  PubMed  Google Scholar 

  12. Wasner G, Schattschneider J, Binder A, Baron R: Topical menthol–a human model for cold pain by activation and sensitization of C nociceptors. Brain 2004, 127(Pt 5):1159–1171.

    Article  PubMed  Google Scholar 

  13. Wasner G, Naleschinski D, Binder A, et al.: The effect of menthol on cold allodynia in patients with neuropathic pain. Pain Med 2008, 9:354–358.

    Article  PubMed  Google Scholar 

  14. Baron R, Levine JD, Fields HL: Causalgia and reflex sympathetic dystrophy: does the sympathetic nervous system contribute to the generation of pain? Muscle Nerve 1999, 22:678–695.

    Article  CAS  PubMed  Google Scholar 

  15. Baron R, Schattschneider J, Binder A, et al.: Relation between sympathetic vasoconstrictor activity and pain and hyperalgesia in complex regional pain syndromes: a case-control study. Lancet 2002, 359:1655–1660.

    Article  CAS  PubMed  Google Scholar 

  16. Ali Z, Raja SN, Wesselmann U, et al.: Intradermal injection of norepinephrine evokes pain in patients with sympathetically maintained pain. Pain 2000, 88:161–168.

    Article  CAS  PubMed  Google Scholar 

  17. • Oaklander AL, Rissmiller JG, Gelman LB, et al.: Evidence of focal small-fiber axonal degeneration in complex regional pain syndrome-I (reflex sympathetic dystrophy). Pain 2006, 120:235–243. The results of this article support the hypothesis that CRPS I is specifically associated with post-traumatic focal minimal distal nerve injury, affecting nociceptive small fibers.

    Article  PubMed  Google Scholar 

  18. Albrecht PJ, Hines S, Eisenberg E, et al.: Pathologic alterations of cutaneous innervation and vasculature in affected limbs from patients with complex regional pain syndrome. Pain 2006, 120:244–266.

    Article  PubMed  Google Scholar 

  19. Jänig W, Baron R: Is CRPS I a neuropathic pain syndrome? Pain 2006, 120:227–229.

    Article  PubMed  Google Scholar 

  20. Eisenberg E, Shtahl S, Geller R, et al.: Serum and salivary oxidative analysis in complex regional pain syndrome. Pain 2008, 138:226–232.

    Article  CAS  PubMed  Google Scholar 

  21. Baron R, Sommer C, Tölle TR, et al.: Diagnostik und Therapie neuropathischer Schmerzen. In Leitlinien für Diagnostik und Therapie in der Neurologie, edn 4. Edited by Diener HC, Putzki N, Berlit P. Thieme: Stuttgart; 2008, 622–639

  22. Uçeyler N, Eberle T, Rolke R, et al.: Differential expression patterns of cytokines in complex regional pain syndrome. Pain 2007, 132:195–205.

    Article  PubMed  Google Scholar 

  23. Huygen FJ, De Bruijn AG, De Bruin MT, et al.: Evidence for local inflammation in complex regional pain syndrome type 1. Mediators Inflamm 2002, 11:47–51.

    Article  CAS  PubMed  Google Scholar 

  24. Maihöfner C, Handwerker HO, Neundörfer B, Birklein F: Mechanical hyperalgesia in complex regional pain syndrome: a role for TNF-alpha? Neurology 2005, 65:311–313.

    Article  PubMed  Google Scholar 

  25. Alexander GM, van Rijn MA, van Hilten JJ, et al.: Changes in cerebrospinal fluid levels of pro-inflammatory cytokines in CRPS. Pain 2005, 116:213–219.

    Article  CAS  PubMed  Google Scholar 

  26. Wesseldijk F, Huygen FJ, Heijmans-Antonissen C, et al.: Tumor necrosis factor-alpha and interleukin-6 are not correlated with the characteristics of Complex Regional Pain Syndrome type 1 in 66 patients. Eur J Pain 2008, 12:716–721.

    Article  CAS  PubMed  Google Scholar 

  27. Bernateck M, Rolke R, Birklein F, et al.: Successful intravenous regional block with low-dose tumor necrosis factor-alpha antibody infliximab for treatment of complex regional pain syndrome 1. Anesth Analg 2007, 105:1148–1151, table of contents.

    Google Scholar 

  28. • Kohr D, Tschernatsch M, Schmitz K, et al.: Autoantibodies in complex regional pain syndrome bind to a differentiation-dependent neuronal surface autoantigen. Pain 2009, 143:246–251. This article discusses an autoimmune hypothesis in CRPS patients. The authors showed that about 30% to 40% of CRPS patients have surface-binding autoantibodies against an inducible autonomic nervous system autoantigen.

    Article  CAS  PubMed  Google Scholar 

  29. Blaes F, Tschernatsch M, Braeu ME, et al.: Autoimmunity in complex-regional pain syndrome. Ann N Y Acad Sci 2007, 1107:168–173.

    Article  CAS  PubMed  Google Scholar 

  30. Birklein F, Schmelz M, Schifter S, Weber M: The important role of neuropeptides in complex regional pain syndrome. Neurology 2001, 57:2179–2184.

    CAS  PubMed  Google Scholar 

  31. Weber M, Birklein F, Neundörfer B, Schmelz M: Facilitated neurogenic inflammation in complex regional pain syndrome. Pain 2001, 91:251–257.

    Article  CAS  PubMed  Google Scholar 

  32. Leitha T, Korpan M, Staudenherz A, et al.: Five phase bone scintigraphy supports the pathophysiological concept of a subclinical inflammatory process in reflex sympathetic dystrophy. Q J Nucl Med 1996, 40:188–193.

    CAS  PubMed  Google Scholar 

  33. Renier JC, Arlet J, Bregeon C, et al.: The joint in algodystrophy. Joint fluid, synovium, cartilage [in French]. Rev Rhum Mal Osteoartic 1983, 50:255–260.

    CAS  PubMed  Google Scholar 

  34. Graif M, Schweitzer ME, Marks B, et al.: Synovial effusion in reflex sympathetic dystrophy: an additional sign for diagnosis and staging. Skeletal Radiol 1998, 27:262–265.

    Article  CAS  PubMed  Google Scholar 

  35. Oyen WJ, Arntz IE, Claessens RM, et al.: Reflex sympathetic dystrophy of the hand: an excessive inflammatory response? Pain 1993, 55:151–157.

    Article  CAS  PubMed  Google Scholar 

  36. de Mos M, Huygen FJ, Stricker BH, et al.: The association between ACE inhibitors and the complex regional pain syndrome: suggestions for a neuro-inflammatory pathogenesis of CRPS. Pain 2009, 142:218–224.

    Article  PubMed  Google Scholar 

  37. Baron R, Jänig W: Complex regional pain syndromes–how do we escape the diagnostic trap? Lancet 2004, 364:1739–1741.

    Article  PubMed  Google Scholar 

Download references

Disclosure

Dr. Dennis Naleschinski has received speaker`s honoraria from Genzyme, Pfizer, and Grünenthal. Dr. Ralf Baron has received consultant speaker honoraria from Pfizer, Genzyme, Grünenthal, Mundipharma, Allergan, Sanofi Pasteur, Medtronic, Eisai, UCB, Eli Lilly, and Astellas, and grant research support from Pfizer, Genzyme, and Grünenthal.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ralf Baron.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Naleschinski, D., Baron, R. Complex Regional Pain Syndrome Type I: Neuropathic or Not?. Curr Pain Headache Rep 14, 196–202 (2010). https://doi.org/10.1007/s11916-010-0115-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11916-010-0115-9

Keywords

Navigation