Skip to main content
Top
Published in: Current Pain and Headache Reports 2/2018

01-02-2018 | Other Pain (A Kaye and N Vadivelu, Section Editors)

Complex Regional Pain Syndrome, Current Concepts and Treatment Options

Authors: Ivan Urits, Abra H. Shen, Mark R. Jones, Omar Viswanath, Alan D. Kaye

Published in: Current Pain and Headache Reports | Issue 2/2018

Login to get access

Abstract

Purpose of Review

Complex regional pain syndrome (CRPS) refers to a chronic pain condition that is characterized by progressively worsening spontaneous regional pain without dermatomal distribution. The symptomatology includes pain out of proportion in time and severity to the inciting event. The purpose of this review is to present the most current information concerning epidemiology, diagnosis, pathophysiology, and therapy for CRPS.

Recent Findings

In recent years, discovery of pathophysiologic mechanisms of CRPS has led to significant strides in the understanding of the disease process.

Summary

Continued elucidation of the underlying pathophysiological mechanisms will allow for the development of more targeted and effective evidence-based therapy protocols. Further large clinical trials are needed to investigate mechanisms and treatment of the disorder.
Literature
1.
go back to reference Bruehl S, Bruehl S. Complex regional pain syndrome. BMJ. 2016;38:82–6. Bruehl S, Bruehl S. Complex regional pain syndrome. BMJ. 2016;38:82–6.
2.
go back to reference Van Velzen GAJ, Perez RSGM, Van Gestel MA, Huygen FJPM, Van Kleef M, Van Eijs F, et al. Health-related quality of life in 975 patients with complex regional pain syndrome type 1. Pain. 2014;155:629–34.CrossRefPubMed Van Velzen GAJ, Perez RSGM, Van Gestel MA, Huygen FJPM, Van Kleef M, Van Eijs F, et al. Health-related quality of life in 975 patients with complex regional pain syndrome type 1. Pain. 2014;155:629–34.CrossRefPubMed
3.
go back to reference Merskey H, Bogduk N. Classification of chronic pain. IASP Pain Terminol. 1994. Merskey H, Bogduk N. Classification of chronic pain. IASP Pain Terminol. 1994.
9.
go back to reference •• Harden RN, Maihofner C, Abousaad E, Vatine J, Kirsling A. Validation of the complex regional pain syndrome severity score. 2017;158:1430–6. Clinical use. •• Harden RN, Maihofner C, Abousaad E, Vatine J, Kirsling A. Validation of the complex regional pain syndrome severity score. 2017;158:1430–6. Clinical use.
10.
go back to reference 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(1–2):199–207.CrossRefPubMed 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(1–2):199–207.CrossRefPubMed
11.
go back to reference •• Elsharydah A, Loo NH, Minhajuddin A, Kandil ES. Complex regional pain syndrome type 1 predictors—epidemiological perspective from a national database analysis. J Clin Anesth. 2017;39:34–7. Nationwide epidemiological study.CrossRefPubMed •• Elsharydah A, Loo NH, Minhajuddin A, Kandil ES. Complex regional pain syndrome type 1 predictors—epidemiological perspective from a national database analysis. J Clin Anesth. 2017;39:34–7. Nationwide epidemiological study.CrossRefPubMed
14.
go back to reference Jellad A, Salah S, Ben Salah Frih Z. Complex regional pain syndrome type I: incidence and risk factors in patients with fracture of the distal radius. Arch Phys Med Rehabil. 2014;95:487–92.CrossRefPubMed Jellad A, Salah S, Ben Salah Frih Z. Complex regional pain syndrome type I: incidence and risk factors in patients with fracture of the distal radius. Arch Phys Med Rehabil. 2014;95:487–92.CrossRefPubMed
15.
go back to reference Beerthuizen A, Stronks DL, Van’T Spijker A, Yaksh A, Hanraets BM, Klein J, et al. Demographic and medical parameters in the development of complex regional pain syndrome type 1 (CRPS1): prospective study on 596 patients with a fracture. Pain. 2012;153:1187–92.CrossRefPubMed Beerthuizen A, Stronks DL, Van’T Spijker A, Yaksh A, Hanraets BM, Klein J, et al. Demographic and medical parameters in the development of complex regional pain syndrome type 1 (CRPS1): prospective study on 596 patients with a fracture. Pain. 2012;153:1187–92.CrossRefPubMed
16.
go back to reference Pons T, Shipton EA, Williman J, Mulder RT. Potential risk factors for the onset of complex regional pain syndrome type 1: a systematic literature review. Hindawi Publishing Corporation; 2015;2015. Pons T, Shipton EA, Williman J, Mulder RT. Potential risk factors for the onset of complex regional pain syndrome type 1: a systematic literature review. Hindawi Publishing Corporation; 2015;2015.
17.
go back to reference Brunner F, Bachmann LM, Perez RSGM, Marinus J, Wertli MM. Painful swelling after a noxious event and the development of complex regional pain syndrome 1: a one-year prospective study. Eur J Pain. 2017;21:1–7.CrossRef Brunner F, Bachmann LM, Perez RSGM, Marinus J, Wertli MM. Painful swelling after a noxious event and the development of complex regional pain syndrome 1: a one-year prospective study. Eur J Pain. 2017;21:1–7.CrossRef
20.
go back to reference Da Costa VV, De Oliveira SB, Fernandes M d CB, Saraiva RÂ. Incidence of regional pain syndrome after carpal tunnel release. Is there a correlation with the anesthetic technique? Rev Bras Anestesiol. 2011;61:425–33.CrossRefPubMed Da Costa VV, De Oliveira SB, Fernandes M d CB, Saraiva RÂ. Incidence of regional pain syndrome after carpal tunnel release. Is there a correlation with the anesthetic technique? Rev Bras Anestesiol. 2011;61:425–33.CrossRefPubMed
22.
go back to reference Marinus J, Moseley GL, Birklein F, Baron R, Maihöfner C, Kingery WS, et al. Clinical features and pathophysiology of complex regional pain syndrome. Lancet Neurol. 2011;10:637–48.CrossRefPubMedPubMedCentral Marinus J, Moseley GL, Birklein F, Baron R, Maihöfner C, Kingery WS, et al. Clinical features and pathophysiology of complex regional pain syndrome. Lancet Neurol. 2011;10:637–48.CrossRefPubMedPubMedCentral
23.
go back to reference Littlejohn G. Neurogenic neuroinflammation in fibromyalgia and complex regional pain syndrome. Nat Rev Rheumatol. 2015;11:639–48.CrossRefPubMed Littlejohn G. Neurogenic neuroinflammation in fibromyalgia and complex regional pain syndrome. Nat Rev Rheumatol. 2015;11:639–48.CrossRefPubMed
33.
go back to reference • Ne OC, Bm W, Mcauley J, Marston L, Gl M. Interventions for treating pain and disability in adults with complex regional pain syndrome—an overview of systematic reviews (Review). Cochrane Libr. 2013;1–68. Systematic review. • Ne OC, Bm W, Mcauley J, Marston L, Gl M. Interventions for treating pain and disability in adults with complex regional pain syndrome—an overview of systematic reviews (Review). Cochrane Libr. 2013;1–68. Systematic review.
35.
go back to reference Azqueta-Gavaldon M, Schulte-Göcking H, Storz C, Azad S, Reiners A, Borsook D, et al. Basal ganglia dysfunction in complex regional pain syndrome—a valid hypothesis? Eur J Pain (United Kingdom). 2017;21:415–24. Azqueta-Gavaldon M, Schulte-Göcking H, Storz C, Azad S, Reiners A, Borsook D, et al. Basal ganglia dysfunction in complex regional pain syndrome—a valid hypothesis? Eur J Pain (United Kingdom). 2017;21:415–24.
36.
go back to reference Hotta J, Saari J, Koskinen M, Hlushchuk Y, Forss N, Hari R. Abnormal brain responses to action observation in complex regional pain syndrome. J Pain Elsevier Inc. 2017;18:255–65. Hotta J, Saari J, Koskinen M, Hlushchuk Y, Forss N, Hari R. Abnormal brain responses to action observation in complex regional pain syndrome. J Pain Elsevier Inc. 2017;18:255–65.
39.
go back to reference • Di Pietro F, Mcauley JH, Parkitny L, Lotze M, Wand BM, Moseley GL, et al. Primary somatosensory cortex function in complex regional pain syndrome: a systematic review and meta-analysis. J Pain. 2013;14:1001–18. Systematic review. CrossRefPubMed • Di Pietro F, Mcauley JH, Parkitny L, Lotze M, Wand BM, Moseley GL, et al. Primary somatosensory cortex function in complex regional pain syndrome: a systematic review and meta-analysis. J Pain. 2013;14:1001–18. Systematic review. CrossRefPubMed
40.
go back to reference Goebel A, Blaes F. Complex regional pain syndrome, prototype of a novel kind of autoimmune disease. Autoimmun Rev. 2013;12:682–6.CrossRefPubMed Goebel A, Blaes F. Complex regional pain syndrome, prototype of a novel kind of autoimmune disease. Autoimmun Rev. 2013;12:682–6.CrossRefPubMed
41.
go back to reference Kohr D, Singh P, Tschernatsch M, Kaps M, Pouokam E, Diener M, et al. Autoimmunity against the β 2 adrenergic receptor and muscarinic-2 receptor in complex regional pain syndrome. Pain. 2011;152:2690–700.CrossRefPubMed Kohr D, Singh P, Tschernatsch M, Kaps M, Pouokam E, Diener M, et al. Autoimmunity against the β 2 adrenergic receptor and muscarinic-2 receptor in complex regional pain syndrome. Pain. 2011;152:2690–700.CrossRefPubMed
42.
go back to reference Guo T, Shi X, Li W, Wei T, David J, Kingery WS. Passive transfer autoimmunity in a mouse model of complex regional pain syndrome. 2017. Guo T, Shi X, Li W, Wei T, David J, Kingery WS. Passive transfer autoimmunity in a mouse model of complex regional pain syndrome. 2017.
43.
go back to reference Dubuis E, Thompson V, Leite MI, Blaes F, Maihöfner C, Greensmith D, et al. Longstanding complex regional pain syndrome is associated with activating autoantibodies against alpha-1a adrenoceptors. Pain. 2014;155:2408–17.CrossRefPubMed Dubuis E, Thompson V, Leite MI, Blaes F, Maihöfner C, Greensmith D, et al. Longstanding complex regional pain syndrome is associated with activating autoantibodies against alpha-1a adrenoceptors. Pain. 2014;155:2408–17.CrossRefPubMed
51.
go back to reference Evaniew N, Mccarthy C, Kleinlugtenbelt YV, Ghert M, Bhandari M. Vitamin C to prevent complex regional pain syndrome in patients with distal radius fractures: a meta-analysis of randomized controlled trials. J Orthop Trauma. 2015;29:235–41.CrossRef Evaniew N, Mccarthy C, Kleinlugtenbelt YV, Ghert M, Bhandari M. Vitamin C to prevent complex regional pain syndrome in patients with distal radius fractures: a meta-analysis of randomized controlled trials. J Orthop Trauma. 2015;29:235–41.CrossRef
53.
go back to reference • Smart K, Wand B, O’Connell N. A Cochrane systematic review of physiotherapy for pain and disability in adults with complex regional pain syndrome (CRPS). Univ Notre Dame Aust - Sch Physiother. 2015. Systematic review. • Smart K, Wand B, O’Connell N. A Cochrane systematic review of physiotherapy for pain and disability in adults with complex regional pain syndrome (CRPS). Univ Notre Dame Aust - Sch Physiother. 2015. Systematic review.
55.
go back to reference • Chevreau M, Romand X, Gaudin P, Juvin R, Baillet A. Bisphosphonates for treatment of complex regional pain syndrome type 1: a systematic literature review and meta-analysis of randomized controlled trials versus placebo. Jt Bone Spine Société Française de Rhumatologie. 2017;84(4):393–9. Large meta-analysis. https://doi.org/10.1016/j.jbspin.2017.03.009.CrossRef • Chevreau M, Romand X, Gaudin P, Juvin R, Baillet A. Bisphosphonates for treatment of complex regional pain syndrome type 1: a systematic literature review and meta-analysis of randomized controlled trials versus placebo. Jt Bone Spine Société Française de Rhumatologie. 2017;84(4):393–9. Large meta-analysis. https://​doi.​org/​10.​1016/​j.​jbspin.​2017.​03.​009.CrossRef
56.
go back to reference Straube S, Derry S, Moore RA, McQuay HJ. Cervico-thoracic or lumbar sympathectomy for neuropathic pain and complex regional pain syndrome. Cochrane Database Syst Rev. 2010;CD002918. Straube S, Derry S, Moore RA, McQuay HJ. Cervico-thoracic or lumbar sympathectomy for neuropathic pain and complex regional pain syndrome. Cochrane Database Syst Rev. 2010;CD002918.
62.
go back to reference Kriek N, Schreurs MWJ, Groeneweg JG, Dik WA, Tjiang GCH, Gültuna I, et al. Spinal cord stimulation in patients with complex regional pain syndrome: a possible target for immunomodulation? Neuromodulation Technol Neural Interface. 2017;2017 Kriek N, Schreurs MWJ, Groeneweg JG, Dik WA, Tjiang GCH, Gültuna I, et al. Spinal cord stimulation in patients with complex regional pain syndrome: a possible target for immunomodulation? Neuromodulation Technol Neural Interface. 2017;2017
67.
go back to reference Bennett GJ. Update on the neurophysiology of pain transmission and modulation: focus on the NMDA-receptor. J Pain Symptom Manag. 2000;19:S2–6.CrossRef Bennett GJ. Update on the neurophysiology of pain transmission and modulation: focus on the NMDA-receptor. J Pain Symptom Manag. 2000;19:S2–6.CrossRef
70.
go back to reference Beaudoin FL, Lin C, Guan W, Merchant RC. Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: results of a randomized, double-blind, clinical trial. Acad Emerg Med. 2014;21:1194–202.CrossRef Beaudoin FL, Lin C, Guan W, Merchant RC. Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: results of a randomized, double-blind, clinical trial. Acad Emerg Med. 2014;21:1194–202.CrossRef
72.
go back to reference Becerra L, Schwartzman RJ, Kiefer RT, Rohr P, Moulton EA, Wallin D, et al. CNS measures of pain responses pre- and post-anesthetic ketamine in a patient with complex regional pain syndrome. Pain Med (United States). 2015;16:2368–85. Becerra L, Schwartzman RJ, Kiefer RT, Rohr P, Moulton EA, Wallin D, et al. CNS measures of pain responses pre- and post-anesthetic ketamine in a patient with complex regional pain syndrome. Pain Med (United States). 2015;16:2368–85.
76.
go back to reference Puchalski P, Zyluk A. Results of the treatment of chronic, refractory CRPS with ketamine infusions: a preliminary report. Handchirurgie Mikrochirurgie Plast Chir. 2016;48:143–7.CrossRef Puchalski P, Zyluk A. Results of the treatment of chronic, refractory CRPS with ketamine infusions: a preliminary report. Handchirurgie Mikrochirurgie Plast Chir. 2016;48:143–7.CrossRef
77.
go back to reference Zuniga RE, Perera S, Abram SE. Intrathecal baclofen: a useful agent in the treatment of well-established complex regional pain syndrome. Reg Anesth Pain Med. 2002;27(1):90–3.PubMed Zuniga RE, Perera S, Abram SE. Intrathecal baclofen: a useful agent in the treatment of well-established complex regional pain syndrome. Reg Anesth Pain Med. 2002;27(1):90–3.PubMed
78.
go back to reference Penn R, Kroin J. Intrathecal baclofen alleviates spinal cord spasticity. Lancet. 1984;1078. Penn R, Kroin J. Intrathecal baclofen alleviates spinal cord spasticity. Lancet. 1984;1078.
80.
go back to reference van Rijn MA, Munts AG, Marinus J, Voormolen JHC, de Boer KS, Teepe-Twiss IM, et al. Intrathecal baclofen for dystonia of complex regional pain syndrome. Pain. 2009;143:41–7.CrossRefPubMed van Rijn MA, Munts AG, Marinus J, Voormolen JHC, de Boer KS, Teepe-Twiss IM, et al. Intrathecal baclofen for dystonia of complex regional pain syndrome. Pain. 2009;143:41–7.CrossRefPubMed
82.
83.
go back to reference Renier JC, Basle M, Arlet J, Seret P, Acquaviva P, Schiano A, et al. Bone and phosphoro-calcium metabolism in reflex sympathetic dystrophy. Rev Rhum Mal Osteoartic. 1983;50(1):23–31.PubMed Renier JC, Basle M, Arlet J, Seret P, Acquaviva P, Schiano A, et al. Bone and phosphoro-calcium metabolism in reflex sympathetic dystrophy. Rev Rhum Mal Osteoartic. 1983;50(1):23–31.PubMed
84.
go back to reference Varenna M, Adami S, Sinigaglia L. Bisphosphonates in complex regional pain syndrome type I: how do they work? Clin Exp Rheumatol. 2014;32(4):451–4.PubMed Varenna M, Adami S, Sinigaglia L. Bisphosphonates in complex regional pain syndrome type I: how do they work? Clin Exp Rheumatol. 2014;32(4):451–4.PubMed
87.
go back to reference O’Connell NE, Wand BM, McAuley J, Marston L, Moseley GL. Interventions for treating pain and disability in adults with complex regional pain syndrome—an overview of systematic reviews. In: O’Connell NE, editor. Cochrane database Syst. Rev. Chichester: John Wiley & Sons, Ltd; 2013. https://doi.org/10.1002/14651858.CD009416.pub2. O’Connell NE, Wand BM, McAuley J, Marston L, Moseley GL. Interventions for treating pain and disability in adults with complex regional pain syndrome—an overview of systematic reviews. In: O’Connell NE, editor. Cochrane database Syst. Rev. Chichester: John Wiley & Sons, Ltd; 2013. https://​doi.​org/​10.​1002/​14651858.​CD009416.​pub2.
88.
go back to reference Goebel A, Bisla J, Carganillo R, Cole C, Frank B, Gupta R, et al. A randomised placebo-controlled phase III multicentre trial: low-dose intravenous immunoglobulin treatment for long-standing complex regional pain syndrome (LIPS trial). A randomised placebo-controlled Phase III multicentre trial low-dose Intraven. immunoglobulin Treat. long-standing complex Reg. pain Syndr. (LIPS trial). NIHR J Libr. 2017. Goebel A, Bisla J, Carganillo R, Cole C, Frank B, Gupta R, et al. A randomised placebo-controlled phase III multicentre trial: low-dose intravenous immunoglobulin treatment for long-standing complex regional pain syndrome (LIPS trial). A randomised placebo-controlled Phase III multicentre trial low-dose Intraven. immunoglobulin Treat. long-standing complex Reg. pain Syndr. (LIPS trial). NIHR J Libr. 2017.
89.
go back to reference Jaiman A, Lokesh M, Neogi DS. Effect of vitamin C on prevention of complex regional pain syndrome type I in foot and ankle surgery. Foot Ankle Surg. 2011;207. Jaiman A, Lokesh M, Neogi DS. Effect of vitamin C on prevention of complex regional pain syndrome type I in foot and ankle surgery. Foot Ankle Surg. 2011;207.
90.
go back to reference Shibuya N, Humphers JM, Agarwal MR, Jupiter DC. Efficacy and safety of high-dose vitamin C on complex regional pain syndrome in extremity trauma and surgery—systematic review and meta-analysis. J Foot Ankle Surg. 2013;52:62–6.CrossRefPubMed Shibuya N, Humphers JM, Agarwal MR, Jupiter DC. Efficacy and safety of high-dose vitamin C on complex regional pain syndrome in extremity trauma and surgery—systematic review and meta-analysis. J Foot Ankle Surg. 2013;52:62–6.CrossRefPubMed
91.
95.
go back to reference Midbari A, Suzan E, Adler T, Melamed E, Norman D, Vulfsons S, et al. Amputation in patients with complex regional pain syndrome: a comparative study between amputees and non-amputees with intractable disease. Bone Joint J. 2016;98–B:548–54.CrossRefPubMed Midbari A, Suzan E, Adler T, Melamed E, Norman D, Vulfsons S, et al. Amputation in patients with complex regional pain syndrome: a comparative study between amputees and non-amputees with intractable disease. Bone Joint J. 2016;98–B:548–54.CrossRefPubMed
Metadata
Title
Complex Regional Pain Syndrome, Current Concepts and Treatment Options
Authors
Ivan Urits
Abra H. Shen
Mark R. Jones
Omar Viswanath
Alan D. Kaye
Publication date
01-02-2018
Publisher
Springer US
Published in
Current Pain and Headache Reports / Issue 2/2018
Print ISSN: 1531-3433
Electronic ISSN: 1534-3081
DOI
https://doi.org/10.1007/s11916-018-0667-7

Other articles of this Issue 2/2018

Current Pain and Headache Reports 2/2018 Go to the issue

Chronic Daily Headache (S-J Wang, Section Editor)

Migraine and the Hippocampus

Childhood and Adolescent Headache (S Evers, Section Editor)

Pediatric Intracranial Hypertension: a Current Literature Review