Abstract
The awareness of complex regional pain syndrome (CRPS) in the pediatric population is increasing. The condition involves regional pain that is out of proportion to any initiating event (if there is one) and is associated with sensory, functional, autonomic, and inflammatory changes in the region of the pain. The signs and symptoms of CRPS can vary between patients and stage of the disease process. Like many chronic pain conditions, it is often associated with significant disability and a detrimental effect on quality of life. It has a complex pathophysiology that remains poorly understood but provides many potential targets for treatments. Management involves a biopsychosocial formulation that encompasses physical and psychological interventions alongside pharmacological strategies. We review the current evidence for the treatment of this condition in children, with particular reference to pharmacological management.
Similar content being viewed by others
References
International Association for the Study of Pain. Classification of chronic pain. 2nd edition (revised). 2012. http://www.iasp-pain.org/files/Content/ContentFolders/Publications2/ClassificationofChronicPain/Part_II-A.pdf.
Bruehl S. Complex regional pain syndrome. BMJ. 2015;351:h2730.
Abu-Arafeh H, Abu-Arafeh I. Complex regional pain syndrome in children: incidence and clinical characteristics. Arch Dis Child. [Epub 22 Mar 2016].
Stanton-Hicks M. Plasticity of complex regional pain syndrome (CRPS) in children. Pain Med. 2010;11(8):1216–23.
Kachko L, Efrat R, Ben Ami S, Mukamel M, Katz J. Complex regional pain syndromes in children and adolescents. Pediatr Int. 2008;50(4):523–7.
Tan EC, Zijlstra B, Essink ML, Goris RJ, Severijnen RS. Complex regional pain syndrome type I in children. Acta Paediatr. 2008;97(7):875–9.
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.
de Mos M, de Bruijn AG, Huygen FJ, Dieleman JP, Stricker BH, Sturkenboom MC. The incidence of complex regional pain syndrome: a population-based study. Pain. 2007;129(1–2):12–20.
Bruehl S. An update on the pathophysiology of complex regional pain syndrome. Anesthesiology. 2010;113(3):713–25.
Birklein F, Riedl B, Sieweke N, Weber M, Neundorfer B. Neurological findings in complex regional pain syndromes: analysis of 145 cases. Acta Neurol Scand. 2000;101(4):262–9.
Harden RN, Bruehl S, Perez RS, Birklein F, Marinus J, Maihofner C, et al. Validation of proposed diagnostic criteria (the “Budapest Criteria”) for complex regional pain syndrome. Pain. 2010;150(2):268–74.
Rajapakse D, Liossi C, Howard RF. Presentation and management of chronic pain. Arch Dis Child. 2014;99(5):474–80.
Low AK, Ward K, Wines AP. Pediatric complex regional pain syndrome. J Pediatr Orthop. 2007;27(5):567–72.
Sherry DD, Wallace CA, Kelley C, Kidder M, Sapp L. Short- and long-term outcomes of children with complex regional pain syndrome type I treated with exercise therapy. Clin J Pain. 1999;15(3):218–23.
Berde CB, Lebel A. Complex regional pain syndromes in children and adolescents. Anesthesiology. 2005;102(2):252–5.
Katholi BR, Daghstani SS, Banez GA, Brady KK. Noninvasive treatments for pediatric complex regional pain syndrome: a focused review. PM R. 2014;6(10):926–33.
Stanton-Hicks MD, Burton AW, Bruehl SP, Carr DB, Harden RN, Hassenbusch SJ, et al. An updated interdisciplinary clinical pathway for CRPS: report of an expert panel. Pain Pract. 2002;2(1):1–16.
Maillard SM, Davies K, Khubchandani R, Woo PM, Murray KJ. Reflex sympathetic dystrophy: a multidisciplinary approach. Arthritis Rheum. 2004;51(2):284–90.
Howard RF, Wiener S, Walker SM. Neuropathic pain in children. Arch Dis Child. 2014;99(1):84–9.
Wheeler DS, Vaux KK, Tam DA. Use of gabapentin in the treatment of childhood reflex sympathetic dystrophy. Pediatr Neurol. 2000;22(3):220–1.
Tong HC, Nelson VS. Recurrent and migratory reflex sympathetic dystrophy in children. Pediatr Rehabil. 2000;4(2):87–9.
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.
Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162–73.
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(1):62–6.
Ekrol I, Duckworth AD, Ralston SH, Court-Brown CM, McQueen MM. The influence of vitamin C on the outcome of distal radial fractures: a double-blind, randomized controlled trial. J Bone Joint Surg Am. 2014;96(17):1451–9.
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(2):89–95.
Atalay NS, Ercidogan O, Akkaya N, Sahin F. Prednisolone in complex regional pain syndrome. Pain Physician. 2014;17(2):179–85.
Barbalinardo S, Loer SA, Goebel A, Perez RS. The treatment of longstanding complex regional pain syndrome with oral steroids. Pain Med. [Epub 7 Dec 2015].
Wertli MM, Kessels AG, Perez RS, Bachmann LM, Brunner F. Rational pain management in complex regional pain syndrome 1 (CRPS 1): a network meta-analysis. Pain Med. 2014;15(9):1575–89.
Benzon HT, Liu SS, Buvanendran A. Evolving definitions and pharmacologic management of complex regional pain syndrome. Anesth Analg. 2016;122(3):601–4.
Xu J, Yang J, Lin P, Rosenquist E, Cheng J. Intravenous therapies for complex regional pain syndrome: a systematic review. Anesth Analg. 2016;122(3):843–56.
di Vadi PP, Brill S, Jack T, Brown C, Edwards T. Intravenous regional blocks with guanethidine and prilocaine combined with physiotherapy: two children with complex regional pain syndrome, type 1. Eur J Anaesthesiol. 2002;19(5):384–6.
Suresh S, Wheeler M, Patel A. Case series: IV regional anesthesia with ketorolac and lidocaine: is it effective for the management of complex regional pain syndrome 1 in children and adolescents? Anesth Analg. 2003;96(3):694–5.
Papadopoulos GS, Xenakis TA, Arnaoutoglou E, Tefa L, Kitsoulis PB. The treatment of reflex sympathetic dystrophy in a 9-year-old boy with long standing symptoms. Minerva Anestesiol. 2001;67(9):659–63.
Giusti A, Bianchi G. Treatment of complex regional pain syndrome type I with bisphosphonates. RMD Open. 2015;1(Suppl 1):e000056.
Nama S, Meenan DR, Fritz WT. The use of sub-anesthetic intravenous ketamine and adjuvant dexmedetomidine when treating acute pain from CRPS. Pain Physician. 2010;13(4):365–8.
Patil S, Anitescu M. Efficacy of outpatient ketamine infusions in refractory chronic pain syndromes: a 5-year retrospective analysis. Pain Med. 2012;13(2):263–9.
Goebel A, Jayaseelan S, Sachane K, Gupta M, Frank B. Racemic ketamine 4.5-day infusion treatment of long-standing complex regional pain syndrome-a prospective service evaluation in five patients. Br J Anaesth. 2015;115(1):146–7.
Perez RS, Zollinger PE, Dijkstra PU, Thomassen-Hilgersom IL, Zuurmond WW, Rosenbrand KC, et al. Evidence based guidelines for complex regional pain syndrome type 1. BMC Neurol. 2010;10:20.
Goebel A. Autoantibody pain. Autoimmun Rev. 2016;15(6):552–7.
Aradillas E, Schwartzman RJ, Grothusen JR, Goebel A, Alexander GM. Plasma exchange therapy in patients with complex regional pain syndrome. Pain Physician. 2015;18(4):383–94.
Goebel A, Shenker N, Padfield N, et al. Low-dose intravenous immunoglobulin treatment for complex regional pain syndrome (LIPS): study protocol for a randomized controlled trial. Trials. 2014;15:404.
Goebel A, Jones S, Oomman S, Callaghan T, Sprotte G. Treatment of long-standing complex regional pain syndrome with therapeutic plasma exchange: a preliminary case series of patients treated in 2008–2014. Pain Med. 2014;15(12):2163–4.
Zernikow B, Wager J, Brehmer H, Hirschfeld G, Maier C. Invasive treatments for complex regional pain syndrome in children and adolescents: a scoping review. Anesthesiology. 2015;122(3):699–707.
Dadure C, Motais F, Ricard C, Raux O, Troncin R, Capdevila X. Continuous peripheral nerve blocks at home for treatment of recurrent complex regional pain syndrome I in children. Anesthesiology. 2005;102(2):387–91.
Olsson GL, Meyerson BA, Linderoth B. Spinal cord stimulation in adolescents with complex regional pain syndrome type I (CRPS-I). Eur J Pain. 2008;12(1):53–9.
Eccleston C, Malleson PN, Clinch J, Connell H, Sourbut C. Chronic pain in adolescents: evaluation of a programme of interdisciplinary cognitive behaviour therapy. Arch Dis Child. 2003;88(10):881–5.
Lee BH, Scharff L, Sethna NF, McCarthy CF, Scott-Sutherland J, Shea AM, et al. Physical therapy and cognitive-behavioral treatment for complex regional pain syndromes. J Pediatr. 2002;141(1):135–40.
Murray CS, Cohen A, Perkins T, Davidson JE, Sills JA. Morbidity in reflex sympathetic dystrophy. Arch Dis Child. 2000;82(3):231–3.
Tan EC, van de Sandt-Renkema N, Krabbe PF, Aronson DC, Severijnen RS. Quality of life in adults with childhood-onset of Complex Regional Pain Syndrome type I. Injury. 2009;40(8):901–4.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Dr. Glyn Williams and Dr. Richard Howard have no financial disclosures or conflicts of interest that are directly relevant to the content of this article.
Funding
No sources of funding were used to prepare this manuscript.
Rights and permissions
About this article
Cite this article
Williams, G., Howard, R. The Pharmacological Management of Complex Regional Pain Syndrome in Pediatric Patients. Pediatr Drugs 18, 243–250 (2016). https://doi.org/10.1007/s40272-016-0179-z
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40272-016-0179-z