Skip to main content

Advertisement

SpringerLink
Log in

Pharmacologic therapies for complex regional pain syndrome

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

Abstract

Complex regional pain syndrome (CRPS) remains a challenging condition to diagnose and treat. There are few large-scale, randomized trials of pharmacologic agents, and most published studies are small, uncontrolled, or presented only in abstract form at meetings. The most commonly used agents, such as anticonvulsants, antidepressants, and opiates, have been found to be useful for other neuropathic pain conditions in large-scale trials but have not been adequately studied in CRPS. Systemic steroids delivered by multiple routes continue to be used, with some good evidence for short-term administration. N-methyl-D-aspartate antagonists have recently gained in popularity, without evidence from well-controlled trials. Bisphosphonates have been well studied and offer promise. In addition, there has been interest in thalidomide; however, we are still awaiting well-controlled trials. This article presents an overview of the available data regarding pharmacologic therapies for CRPS. These agents should be used in conjunction with a comprehensive interdisciplinary approach aimed at functional restoration and improved quality of life.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Reflex Sympathetic Dystrophy Syndrome Association of America. http://www.rsds.org/. Accessed November 8, 2006.

  2. Stanton-Hicks M: An updated interdisciplinary clinical pathway for CRPS: report of an expert panel. Pain Practice 2002, 2:1–16.

    Article  PubMed  Google Scholar 

  3. Mellick LB, Mellick GA: Successful treatment of reflex sympathetic dystrophy with gabapentin. Am J Emerg Med 1995, 13:96.

    Article  PubMed  CAS  Google Scholar 

  4. Fink K, Dooley DJ, Meder WP, et al.: Inhibition of neuronal Ca(2+) influx by gabapentin and pregabalin in the human neocortex. Neuropharmacology 2002, 42:229–236.

    Article  PubMed  CAS  Google Scholar 

  5. Backonja M, Glanzman RL: Gabapentin dosing for neuropathic pain: evidence from randomized, placebo-controlled clinical trials. Clin Ther 2003, 25:81–104.

    Article  PubMed  CAS  Google Scholar 

  6. Rowbotham M, Harden N, Stacey B, et al.: Gabapentin for the treatment of postherapetic neuralgia: a randomized controlled trial. JAMA 1998, 280:1837–1842.

    Article  PubMed  CAS  Google Scholar 

  7. 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.

    Article  PubMed  CAS  Google Scholar 

  8. Serpell MG: Gabapentin in neuropathic pain syndromes: a randomised, double-blind, placebo-controlled trial. Pain 2002, 99:557–566.

    Article  PubMed  CAS  Google Scholar 

  9. Gilron I, Bailey JM, Tu D, et al.: Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med 2005, 352:1324–1334.

    Article  PubMed  CAS  Google Scholar 

  10. Dworkin RH, Corbin AE, Young JP Jr, et al.: Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology 2003, 60:1274–1283.

    PubMed  CAS  Google Scholar 

  11. Rosenstock J, Tuchman M, LaMoreaux L, Sharma U: Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial. Pain 2004, 110:628–638.

    Article  PubMed  CAS  Google Scholar 

  12. 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, 92:488–495.

    Article  PubMed  CAS  Google Scholar 

  13. Beydoun A, Shaibani A, Hopwood M, Wan Y: Oxcarbazepine in painful diabetic neuropathy: results of a dose-ranging study. Acta Neurol Scand 2006, 113:395–404.

    Article  PubMed  CAS  Google Scholar 

  14. Beydoun A, Kobetz SA, Carrazana EJ: Efficacy of oxcarbazepine in the treatment of painful diabetic neuropathy. Clin J Pain 2004, 20:174–178.

    Article  PubMed  Google Scholar 

  15. Sindrup SH, Jensen TS: Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action. Pain 1999, 83:389–400.

    Article  PubMed  CAS  Google Scholar 

  16. Raja SN, Haythornthwaite JA, Pappagallo M, et al.: Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology 2002, 59:1015–1021.

    PubMed  CAS  Google Scholar 

  17. Sudoh Y, Cahoon EE, Gerner P, Wang GK: Tricyclic antidepressants as long-acting local anesthetics. Pain 2003, 103:49–55.

    Article  PubMed  CAS  Google Scholar 

  18. Max MB, Lynch SA, Muir J, et al.: Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy. N Engl J Med 1992, 326:1250–1256.

    Article  PubMed  CAS  Google Scholar 

  19. Sindrup SH, Bach FW, Madsen C, et al.: Venlafaxine versus imipramine in painful polyneuropathy: a randomized, controlled trial. Neurology 2003, 60:1284–1289.

    PubMed  CAS  Google Scholar 

  20. Raskin J, Pritchett YL, Wang F, et al.: A double-blind, randomized multicenter trial comparing duloxetine with placebo in the management of diabetic peripheral neuropathic pain. Pain Med 2005, 6:346–356.

    Article  PubMed  Google Scholar 

  21. Raskin J, Wang F, Pritchett YL, Goldstein DJ: Duloxetine for patients with diabetic peripheral neuropathic pain: a 6-month open-label safety study. Pain Med 2006, 7:373–385.

    Article  PubMed  Google Scholar 

  22. Perahia DG, Pritchett YL, Desaiah D, Raskin J: Efficacy of duloxetine in painful symptoms: an analgesic or antidepressant effect? Int Clin Psychopharmacol 2006, 21:311–317.

    Article  PubMed  Google Scholar 

  23. Dellemijn P: Are opioids effective in relieving neuropathic pain? Pain 1999, 80:453–462.

    Article  PubMed  CAS  Google Scholar 

  24. Watson CP, Babul N: Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia. Neurology 1998, 50:1837–1841.

    PubMed  CAS  Google Scholar 

  25. Watson CP, Moulin D, Watt-Watson J, et al.: Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy. Pain 2003, 105:71–78.

    Article  PubMed  CAS  Google Scholar 

  26. Chu LF, Clark DJ, Angst MS: Opioid tolerance and hyperalgesia in chronic pain patients after one month of oral morphine therapy: a preliminary prospective study. J Pain 2006, 7:43–48.

    Article  PubMed  CAS  Google Scholar 

  27. Daniell HW: Hypogonadism in men consuming sustained-action oral opioids. J Pain 2002, 3:377–384.

    Article  PubMed  Google Scholar 

  28. Zhao Z, Chen SR, Eisenach JC, et al.: Spinal cyclooxygenase-2 is involved in development of allodynia after nerve injury in rats. Neuroscience 2000, 97:743–748.

    Article  PubMed  CAS  Google Scholar 

  29. Ossipov MH, Jerussi TP, Ren K, et al.: Differential effects of spinal (R)-ketoprofen and (S)-ketoprofen against signs of neuropathic pain and tonic nociception: evidence for a novel mechanism of action of (R)-ketoprofen against tactile allodynia. Pain 2000, 87:193–199.

    Article  PubMed  CAS  Google Scholar 

  30. Bianchi C, Rossi S, Turi S, et al.: Long-term functional outcome measures in corticosteroid-treated complex regional pain syndrome. Eura Medicophys 2006, 42:103–111.

    PubMed  CAS  Google Scholar 

  31. Christensen K, Jensen EM, Noer I: The reflex dystrophy syndrome response to treatment with systemic corticosteroids. Acta Chir Scand 1982, 148:653–655.

    PubMed  CAS  Google Scholar 

  32. Kalita J, Vajpayee A, Misra UK: Comparison of prednisolone with piroxicam in complex regional pain syndrome following stroke: a randomized controlled trial. QJM 2006, 99:89–95.

    Article  PubMed  CAS  Google Scholar 

  33. Kingery WS: A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes. Pain 1997, 73:123–139.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  35. Zuurmond WW, Langendijk PN, Bezemer PD, et al.: Treatment of acute reflex sympathetic dystrophy with DMSO 50% in a fatty cream. Acta Anaesthesiol Scand 1996, 40:364–367.

    PubMed  CAS  Google Scholar 

  36. 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, 354:2025–2028.

    Article  PubMed  CAS  Google Scholar 

  37. Pappagallo M, Breuer B, Schneider A, Sperber K: Treatment of chronic mechanical spinal pain with intravenous pamidronate: a review of medical records. J Pain Symptom Manage 2003, 26:678–683.

    Article  PubMed  CAS  Google Scholar 

  38. Kubalek I: Treatment of reflex sympathetic dystrophy with pamidronate: 29 cases. Rheumatology (Oxford) 2001, 40:1394–1397.

    Article  CAS  Google Scholar 

  39. 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, 50:3690–3697.

    Article  PubMed  CAS  Google Scholar 

  40. Adami S, Fossaluzza V, Gatti D, et al.: Bisphosphonate therapy of reflex sympathetic dystrophy syndrome. Ann Rheum Dis 1997, 56:201–204.

    PubMed  CAS  Google Scholar 

  41. Robinson JN, Sandom J, Chapman PT: Efficacy of pamidronate in complex regional pain syndrome type I. Pain Med 2004, 5:276–280.

    Article  PubMed  Google Scholar 

  42. 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, 27:1477–1483.

    PubMed  CAS  Google Scholar 

  43. Galer BS, Miller KV, Rowbotham MC: Response to intravenous lidocaine infusion differs based on clinical diagnosis and site of nervous system injury. Neurology 1993, 43:1233–1235.

    PubMed  CAS  Google Scholar 

  44. Wallace MS, Ridgeway BM, Leung AY, et al.: Concentration-effect relationship of intravenous lidocaine on the allodynia of complex regional pain syndrome types I and II. Anesthesiology 2000, 92:75–83.

    Article  PubMed  CAS  Google Scholar 

  45. Correll GE, Maleki J, Gracely EJ, et al.: Subanesthetic ketamine infusion therapy: a retrospective analysis of a novel therapeutic approach to complex regional pain syndrome. Pain Med 2004, 5:263–275.

    Article  PubMed  Google Scholar 

  46. Nelson KA, Park KM, Robinovitz E, et al.: High-dose oral dextromethorphan versus placebo in painful diabetic neuropathy and postherapetic neuralgia. Neurology 1997, 48:1212–1218.

    PubMed  CAS  Google Scholar 

  47. Galer BS, Lee D, Ma T, et al.: MorphiDex (morphine sulfate/dextromethorphan hydrobromide combination) in the treatment of chronic pain: three multicenter, randomized, double-blind, controlled clinical trials fail to demonstrate enhanced opioid analgesia or reduction in tolerance. Pain 2005, 115:284–295.

    Article  PubMed  CAS  Google Scholar 

  48. Kleinbohl D, Gortelmeyer R, Bender HJ, Holzl R: Amantadine sulfate reduces experimental sensitization and pain in chronic back pain patients. Anesth Analg 2006, 102:840–847.

    Article  PubMed  CAS  Google Scholar 

  49. Maier C, Dertwinkel R, Mansourian N, et al.: Efficacy of the NMDA-receptor antagonist memantine in patients with chronic phantom limb pain—results of a randomized double-blinded, placebo-controlled trial. Pain 2003, 103:277–283.

    Article  PubMed  CAS  Google Scholar 

  50. Te AE: A modern rationale for the use of phenoxybenzamine in urinary tract disorders and other conditions. Clin Ther 2002, 24:851–861; discussion 837.

    Article  PubMed  CAS  Google Scholar 

  51. Muizelaar JP, Kleyer M, Hertogs IA, DeLange DC: Complex regional pain syndrome (reflex sympathetic dystrophy and causalgia): management with the calcium channel blocker nifedipine and/or the alpha-sympathetic blocker phenoxybenzamine in 59 patients. Clin Neurol Neurosurg 1997, 99:26–30.

    Article  PubMed  CAS  Google Scholar 

  52. Raja SN, Turnquist JL, Meleka S, Campbell JN: Monitoring adequacy of alpha-adrenoceptor blockade following systemic phentolamine administration. Pain 1996, 64:197–204.

    Article  PubMed  CAS  Google Scholar 

  53. Davies PS, Galer BS: Review of lidocaine patch 5% studies in the treatment of postherpetic neuralgia. Drugs 2004, 64:937–947.

    Article  PubMed  CAS  Google Scholar 

  54. Devers A, Galer BS: Topical lidocaine patch relieves a variety of neuropathic pain conditions: an open-label study. Clin J Pain 2000, 16:205–208.

    Article  PubMed  CAS  Google Scholar 

  55. Rowbotham MC, Davies PS, Verkempinck C, Galer BS: Lidocaine patch: double-blind controlled study of a new treatment method for post-herpetic neuralgia. Pain 1996, 65:39–44.

    Article  PubMed  CAS  Google Scholar 

  56. Sawynok J: Topical analgesics in neuropathic pain. Curr Pharm Des 2005, 11:2995–3004.

    Article  PubMed  CAS  Google Scholar 

  57. Peikert A, Hentrich M, Ochs G: Topical 0.025% capsaicin in chronic post-herpetic neuralgia: efficacy, predictors of response and long-term course. J Neurol 1991, 238:452–456.

    Article  PubMed  CAS  Google Scholar 

  58. Robbins WR, Staats PS, Levine J, et al.: Treatment of intractable pain with topical large-dose capsaicin: preliminary report. Anesth Analg 1998, 86:579–583.

    Article  PubMed  CAS  Google Scholar 

  59. Ching DW, McClintock A, Beswick F: Successful treatment with low-dose thalidomide in a patient with both Behcet’s disease and complex regional pain syndrome type I: case report. J Clin Rheumatol 2003, 9:96–98.

    Article  PubMed  Google Scholar 

  60. Schwartzman RJ, Chevlen E, Bengtson K: Thalidomide has activity in treating complex regional pain syndrome. Arch Intern Med 2003, 163:1487–1488; author reply 1488.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Stanford University, 780 Welch Road #208, Palo Alto, CA, 94304, USA

    Sean Mackey MD, PhD

Authors
  1. Sean Mackey MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Steven Feinberg MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sean Mackey MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mackey, S., Feinberg, S. Pharmacologic therapies for complex regional pain syndrome. Curr Pain Headache Rep 11, 38–43 (2007). https://doi.org/10.1007/s11916-007-0020-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11916-007-0020-z

Keywords

Search

Navigation