UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Complex regional pain syndrome in adults: Prevention and management

Author
Salahadin Abdi, MD, PhD
Section Editor
Jeremy M Shefner, MD, PhD
Deputy Editor
John F Dashe, MD, PhD

INTRODUCTION

Complex regional pain syndrome (CRPS) is defined as a disorder of the extremities characterized by regional pain that is disproportionate in time or degree to the usual course of any known trauma or other lesion. The pain is not restricted to a specific nerve territory or dermatome and usually has a distal predominance of abnormal sensory, motor, sudomotor, vasomotor, and/or trophic findings. The syndrome shows variable progression over time.

The prevention and management of CRPS will be reviewed here. Other aspects of CRPS in adults and children are presented separately. (See "Complex regional pain syndrome in adults: Pathogenesis, clinical manifestations, and diagnosis" and "Complex regional pain syndrome in children" and "Overview of the treatment of chronic non-cancer pain".)

PREVENTION

The best treatment of CRPS is prevention. Supplementation with vitamin C following fracture or surgery appears to reduce the risk of developing CRPS. Supportive evidence comes from a meta-analysis of four studies that compared daily vitamin C (≥500 mg/day) versus no vitamin C or placebo in patients with trauma or patients having surgery [1]. Two of the studies were randomized controlled trials [2,3] and the other two lacked randomization or blinding [4,5]. Vitamin C treatment was associated with a significant reduction in the development of CRPS (risk ratio 0.22, 95% CI 0.12-0.39) [1].

The largest trial included in the meta-analysis randomly assigned 416 older women with wrist fractures to receive placebo or one of three daily doses (200, 500, or 1500 mg) of vitamin C for 50 days [3]. CRPS was less prevalent in those who received vitamin C (any dose versus placebo, 2.4 versus 10.1 percent). Each of the three doses was statistically superior to placebo, and the higher doses (500 and 1500 mg/day) had greater mean reductions in the relative risk (RR) of CRPS than the lower dose (RR 0.13, 0.17, and 0.41, respectively).

Although the mechanism underlying the beneficial effect of vitamin C is uncertain, there is little risk from use. The optimal dose of vitamin C remains uncertain, but doses of 500 to 1500 mg/day are probably more effective than lower doses. There appears to be no clinically significant difference between 500 mg and 1500 mg daily.

                         

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Wed Aug 17 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. 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.
  2. Zollinger PE, Tuinebreijer WE, Kreis RW, Breederveld RS. Effect of vitamin C on frequency of reflex sympathetic dystrophy in wrist fractures: a randomised trial. Lancet 1999; 354:2025.
  3. Zollinger PE, Tuinebreijer WE, Breederveld RS, Kreis RW. Can vitamin C prevent complex regional pain syndrome in patients with wrist fractures? A randomized, controlled, multicenter dose-response study. J Bone Joint Surg Am 2007; 89:1424.
  4. Besse JL, Gadeyne S, Galand-Desmé S, et al. Effect of vitamin C on prevention of complex regional pain syndrome type I in foot and ankle surgery. Foot Ankle Surg 2009; 15:179.
  5. Cazeneuve JF, Leborgne JM, Kermad K, Hassan Y. [Vitamin C and prevention of reflex sympathetic dystrophy following surgical management of distal radius fractures]. Acta Orthop Belg 2002; 68:481.
  6. Harden RN, Oaklander AL, Burton AW, et al. Complex regional pain syndrome: practical diagnostic and treatment guidelines, 4th edition. Pain Med 2013; 14:180.
  7. McCormick ZL, Gagnon CM, Caldwell M, et al. Short-Term Functional, Emotional, and Pain Outcomes of Patients with Complex Regional Pain Syndrome Treated in a Comprehensive Interdisciplinary Pain Management Program. Pain Med 2015; 16:2357.
  8. Bruehl S, Chung OY. Psychological and behavioral aspects of complex regional pain syndrome management. Clin J Pain 2006; 22:430.
  9. Goebel A, Barker CH, Turner-Stokes L, et al. Complex regional pain syndrome in adults. UK guidelines for diagnosis, referral and management in primary and secondary care. The Royal College of Physicians, London, 2012. https://www.rcplondon.ac.uk/sites/default/files/documents/complex-regional-pain-full-guideline.pdf (Accessed on July 10, 2015).
  10. Gainer MJ. Hypnotherapy for reflex sympathetic dystrophy. Am J Clin Hypn 1992; 34:227.
  11. Kawano M, Matsuoka M, Kurokawa T, et al. Autogenic training as an effective treatment for reflex neurovascular dystrophy: a case report. Acta Paediatr Jpn 1989; 31:500.
  12. Bussa M, Guttilla D, Lucia M, et al. Complex regional pain syndrome type I: a comprehensive review. Acta Anaesthesiol Scand 2015; 59:685.
  13. Freedman M, Greis AC, Marino L, et al. Complex regional pain syndrome: diagnosis and treatment. Phys Med Rehabil Clin N Am 2014; 25:291.
  14. Daly AE, Bialocerkowski AE. Does evidence support physiotherapy management of adult Complex Regional Pain Syndrome Type One? A systematic review. Eur J Pain 2009; 13:339.
  15. Smart KM, Wand BM, O'Connell NE. Physiotherapy for pain and disability in adults with complex regional pain syndrome (CRPS) types I and II. Cochrane Database Syst Rev 2016; 2:CD010853.
  16. McCabe CS, Haigh RC, Blake DR. Mirror visual feedback for the treatment of complex regional pain syndrome (type 1). Curr Pain Headache Rep 2008; 12:103.
  17. Cacchio A, De Blasis E, Necozione S, et al. Mirror therapy for chronic complex regional pain syndrome type 1 and stroke. N Engl J Med 2009; 361:634.
  18. Sato K, Fukumori S, Matsusaki T, et al. Nonimmersive virtual reality mirror visual feedback therapy and its application for the treatment of complex regional pain syndrome: an open-label pilot study. Pain Med 2010; 11:622.
  19. O'Connell NE, Wand BM, McAuley J, et al. Interventions for treating pain and disability in adults with complex regional pain syndrome. Cochrane Database Syst Rev 2013; :CD009416.
  20. Moseley GL. Graded motor imagery for pathologic pain: a randomized controlled trial. Neurology 2006; 67:2129.
  21. Moseley GL. Graded motor imagery is effective for long-standing complex regional pain syndrome: a randomised controlled trial. Pain 2004; 108:192.
  22. Moseley GL. Is successful rehabilitation of complex regional pain syndrome due to sustained attention to the affected limb? A randomised clinical trial. Pain 2005; 114:54.
  23. Ek JW, van Gijn JC, Samwel H, et al. Pain exposure physical therapy may be a safe and effective treatment for longstanding complex regional pain syndrome type 1: a case series. Clin Rehabil 2009; 23:1059.
  24. de Jong JR, Vlaeyen JW, Onghena P, et al. Reduction of pain-related fear in complex regional pain syndrome type I: the application of graded exposure in vivo. Pain 2005; 116:264.
  25. Moseley GL, Zalucki NM, Wiech K. Tactile discrimination, but not tactile stimulation alone, reduces chronic limb pain. Pain 2008; 137:600.
  26. McCabe CS, Haigh RC, Ring EF, et al. A controlled pilot study of the utility of mirror visual feedback in the treatment of complex regional pain syndrome (type 1). Rheumatology (Oxford) 2003; 42:97.
  27. Lewis JS, Kersten P, McPherson KM, et al. Wherever is my arm? Impaired upper limb position accuracy in complex regional pain syndrome. Pain 2010; 149:463.
  28. Watson HK, Carlson L. Treatment of reflex sympathetic dystrophy of the hand with an active "stress loading" program. J Hand Surg Am 1987; 12:779.
  29. McCabe CS, Blake DR. An embarrassment of pain perceptions? Towards an understanding of and explanation for the clinical presentation of CRPS type 1. Rheumatology (Oxford) 2008; 47:1612.
  30. Johnson S, Hall J, Barnett S, et al. Using graded motor imagery for complex regional pain syndrome in clinical practice: failure to improve pain. Eur J Pain 2012; 16:550.
  31. Borchers AT, Gershwin ME. Complex regional pain syndrome: a comprehensive and critical review. Autoimmun Rev 2014; 13:242.
  32. Perez RS, Zollinger PE, Dijkstra PU, et al. Evidence based guidelines for complex regional pain syndrome type 1. BMC Neurol 2010; 10:20.
  33. van de Vusse AC, Stomp-van den Berg SG, Kessels AH, Weber WE. Randomised controlled trial of gabapentin in Complex Regional Pain Syndrome type 1 [ISRCTN84121379]. BMC Neurol 2004; 4:13.
  34. Birklein F, O'Neill D, Schlereth T. Complex regional pain syndrome: An optimistic perspective. Neurology 2015; 84:89.
  35. Wertli MM, Kessels AG, Perez RS, et al. Rational pain management in complex regional pain syndrome 1 (CRPS 1)--a network meta-analysis. Pain Med 2014; 15:1575.
  36. Adami S, Fossaluzza V, Gatti D, et al. Bisphosphonate therapy of reflex sympathetic dystrophy syndrome. Ann Rheum Dis 1997; 56:201.
  37. Manicourt DH, Brasseur JP, Boutsen Y, et al. Role of alendronate in therapy for posttraumatic complex regional pain syndrome type I of the lower extremity. Arthritis Rheum 2004; 50:3690.
  38. Varenna M, Adami S, Rossini M, et al. Treatment of complex regional pain syndrome type I with neridronate: a randomized, double-blind, placebo-controlled study. Rheumatology (Oxford) 2013; 52:534.
  39. Robinson JN, Sandom J, Chapman PT. Efficacy of pamidronate in complex regional pain syndrome type I. Pain Med 2004; 5:276.
  40. Varenna M, Zucchi F, Ghiringhelli D, et al. Intravenous clodronate in the treatment of reflex sympathetic dystrophy syndrome. A randomized, double blind, placebo controlled study. J Rheumatol 2000; 27:1477.
  41. Hanlan AK, Mah-Jones D, Mills PB. Early adjunct treatment with topical lidocaine results in improved pain and function in a patient with complex regional pain syndrome. Pain Physician 2014; 17:E629.
  42. Bickerstaff DR, Kanis JA. The use of nasal calcitonin in the treatment of post-traumatic algodystrophy. Br J Rheumatol 1991; 30:291.
  43. Gobelet C, Waldburger M, Meier JL. The effect of adding calcitonin to physical treatment on reflex sympathetic dystrophy. Pain 1992; 48:171.
  44. Gobelet C, Meier JL, Schaffner W, et al. Calcitonin and reflex sympathetic dystrophy syndrome. Clin Rheumatol 1986; 5:382.
  45. Kalita J, Vajpayee A, Misra UK. Comparison of prednisolone with piroxicam in complex regional pain syndrome following stroke: a randomized controlled trial. QJM 2006; 99:89.
  46. Stanton-Hicks MD, Burton AW, Bruehl SP, et al. An updated interdisciplinary clinical pathway for CRPS: report of an expert panel. Pain Pract 2002; 2:1.
  47. Connolly SB, Prager JP, Harden RN. A systematic review of ketamine for complex regional pain syndrome. Pain Med 2015; 16:943.
  48. Sigtermans MJ, van Hilten JJ, Bauer MC, et al. Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1. Pain 2009; 145:304.
  49. Goebel A, Baranowski A, Maurer K, et al. Intravenous immunoglobulin treatment of the complex regional pain syndrome: a randomized trial. Ann Intern Med 2010; 152:152.
  50. Birklein F, Sommer C. Intravenous immunoglobulin to fight complex regional pain syndromes: hopes and doubts. Ann Intern Med 2010; 152:188.
  51. Harke H, Gretenkort P, Ladleif HU, et al. The response of neuropathic pain and pain in complex regional pain syndrome I to carbamazepine and sustained-release morphine in patients pretreated with spinal cord stimulation: a double-blinded randomized study. Anesth Analg 2001; 92:488.
  52. Stanton-Hicks M. Complex regional pain syndrome: manifestations and the role of neurostimulation in its management. J Pain Symptom Manage 2006; 31:S20.
  53. O'Connell NE, Wand BM, Gibson W, et al. Local anaesthetic sympathetic blockade for complex regional pain syndrome. Cochrane Database Syst Rev 2016; 7:CD004598.
  54. Kemler MA, Barendse GA, van Kleef M, et al. Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy. N Engl J Med 2000; 343:618.
  55. Kemler MA, De Vet HC, Barendse GA, et al. The effect of spinal cord stimulation in patients with chronic reflex sympathetic dystrophy: two years' follow-up of the randomized controlled trial. Ann Neurol 2004; 55:13.
  56. Kemler MA, de Vet HC, Barendse GA, et al. Spinal cord stimulation for chronic reflex sympathetic dystrophy--five-year follow-up. N Engl J Med 2006; 354:2394.
  57. Mailis-Gagnon A, Furlan AD, Sandoval JA, Taylor R. Spinal cord stimulation for chronic pain. Cochrane Database Syst Rev 2004; :CD003783.
  58. Kirkpatrick AF, Derasari M. Transdermal clonidine: treating reflex sympathetic dystrophy. Reg Anesth 1993; 18:140.
  59. Rauck RL, Eisenach JC, Jackson K, et al. Epidural clonidine treatment for refractory reflex sympathetic dystrophy. Anesthesiology 1993; 79:1163.
  60. Straube S, Derry S, Moore RA, Cole P. Cervico-thoracic or lumbar sympathectomy for neuropathic pain and complex regional pain syndrome. Cochrane Database Syst Rev 2013; :CD002918.
  61. Furlan AD, Mailis A, Papagapiou M. Are we paying a high price for surgical sympathectomy? A systematic literature review of late complications. J Pain 2000; 1:245.
  62. van Hilten BJ, van de Beek WJ, Hoff JI, et al. Intrathecal baclofen for the treatment of dystonia in patients with reflex sympathetic dystrophy. N Engl J Med 2000; 343:625.
  63. Kiralp MZ, Yildiz S, Vural D, et al. Effectiveness of hyperbaric oxygen therapy in the treatment of complex regional pain syndrome. J Int Med Res 2004; 32:258.
  64. Veldman PH, Goris RJ. Surgery on extremities with reflex sympathetic dystrophy. Unfallchirurg 1995; 98:45.
  65. Marx C, Wiedersheim P, Michel BA, Stucki G. Preventing recurrence of reflex sympathetic dystrophy in patients requiring an operative intervention at the site of dystrophy after surgery. Clin Rheumatol 2001; 20:114.
  66. Shah RV, Day MR. Recurrence and spread of complex regional pain syndrome caused by remote-site surgery: a case report. Am J Orthop (Belle Mead NJ) 2006; 35:523.
  67. Dadure C, Motais F, Ricard C, et al. Continuous peripheral nerve blocks at home for treatment of recurrent complex regional pain syndrome I in children. Anesthesiology 2005; 102:387.
  68. Monacelli G, Valesini L, Rizzo MI, et al. [Complex Regional Pain (CRPS) Syndrome type II. Timing for surgery and therapeutic options: neuromodulation]. Clin Ter 2006; 157:315.
  69. Brooke V, Janselewitz S. Outcomes of children with complex regional pain syndrome after intensive inpatient rehabilitation. PM R 2012; 4:349.
  70. de Mos M, Huygen FJ, van der Hoeven-Borgman M, et al. Outcome of the complex regional pain syndrome. Clin J Pain 2009; 25:590.
  71. 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.
  72. Allen G, Galer BS, Schwartz L. Epidemiology of complex regional pain syndrome: a retrospective chart review of 134 patients. Pain 1999; 80:539.
  73. Zyluk A. Complex regional pain syndrome type I. Risk factors, prevention and risk of recurrence. J Hand Surg Br 2004; 29:334.
  74. Veldman PH, Goris RJ. Multiple reflex sympathetic dystrophy. Which patients are at risk for developing a recurrence of reflex sympathetic dystrophy in the same or another limb. Pain 1996; 64:463.
  75. Akkus S, Yorgancigil H, Yener M. A case of recurrent and migratory complex regional pain syndrome type I: Prevention by gabapentin. Rheumatol Int 2006; 26:852.