Integrated Psychological, Anesthetic, Nursing, and General Practice Approaches to the Management of Complex Regional Pain Syndrome
Abstract
Background: Complex Regional Pain Syndrome (CRPS) is a debilitating chronic pain condition characterized by severe, disproportionate pain and a constellation of sensory, autonomic, motor, and trophic disturbances. It typically develops after a minor injury or surgery, with a pathophysiology involving neurogenic inflammation, peripheral and central sensitization, autonomic dysregulation, and immune system involvement.
Aim: This article aims to provide a comprehensive review of CRPS, synthesizing current evidence on its etiology, epidemiology, and the underlying pathophysiological mechanisms. Its primary focus is to outline a holistic, integrated management approach that combines medical, rehabilitative, psychological, and interventional strategies.
Methods: The study is a detailed narrative review, consolidating evidence from clinical studies, systematic reviews, and expert guidelines. It evaluates diagnostic criteria (notably the Budapest Criteria), various treatment modalities including physical therapy, pharmacotherapy, psychological interventions, and neuromodulation techniques like spinal cord stimulation.
Results: The review finds that CRPS is a multifactorial disorder with no single curative treatment. Effective management hinges on early diagnosis and a proactive, multidisciplinary strategy. Core components include physical and occupational therapy to restore function, pharmacotherapy (e.g., corticosteroids, bisphosphonates, anticonvulsants) for symptom control, and psychological support to address pain-related distress. For refractory cases, interventional procedures such as sympathetic nerve blocks or neuromodulation can provide significant pain relief and improve quality of life.
Conclusion: A coordinated, interprofessional approach is fundamental to managing CRPS, offering the best opportunity to reduce pain, prevent disability, and improve patient outcomes.
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References
Stanton-Hicks MD. CRPS: what's in a name? Taxonomy, epidemiology, neurologic, immune and autoimmune considerations. Reg Anesth Pain Med. 2019 Mar;44(3):376-387.
Goebel A. Complex regional pain syndrome in adults. Rheumatology (Oxford). 2011 Oct;50(10):1739-50.
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 Feb 24;2(2):CD010853.
de Rooij AM, Perez RS, Huygen FJ, van Eijs F, van Kleef M, Bauer MC, van Hilten JJ, Marinus J. Spontaneous onset of complex regional pain syndrome. Eur J Pain. 2010 May;14(5):510-3.
Iolascon G, de Sire A, Moretti A, Gimigliano F. Complex regional pain syndrome (CRPS) type I: historical perspective and critical issues. Clin Cases Miner Bone Metab. 2015 Jan-Apr;12(Suppl 1):4-10.
Shim H, Rose J, Halle S, Shekane P. Complex regional pain syndrome: a narrative review for the practising clinician. Br J Anaesth. 2019 Aug;123(2):e424-e433.
Harden NR, Bruehl S, Perez RSGM, Birklein F, Marinus J, Maihofner C, Lubenow T, Buvanendran A, Mackey S, Graciosa J, Mogilevski M, Ramsden C, Chont M, Vatine JJ. Validation of proposed diagnostic criteria (the "Budapest Criteria") for Complex Regional Pain Syndrome. Pain. 2010 Aug;150(2):268-274.
Bruehl S. Complex regional pain syndrome. BMJ. 2015 Jul 29;351:h2730.
Bruehl S. An update on the pathophysiology of complex regional pain syndrome. Anesthesiology. 2010 Sep;113(3):713-25.
Galer BS, Henderson J, Perander J, Jensen MP. Course of symptoms and quality of life measurement in Complex Regional Pain Syndrome: a pilot survey. J Pain Symptom Manage. 2000 Oct;20(4):286-92.
Lohnberg JA, Altmaier EM. A review of psychosocial factors in complex regional pain syndrome. J Clin Psychol Med Settings. 2013 Jun;20(2):247-54.
Beerthuizen A, Stronks DL, Van't Spijker A, Yaksh A, Hanraets BM, Klein J, Huygen FJPM. 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 Jun;153(6):1187-1192.
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 Oct;21(9):1611-1617.
Schürmann M, Gradl G, Zaspel J, Kayser M, Löhr P, Andress HJ. Peripheral sympathetic function as a predictor of complex regional pain syndrome type I (CRPS I) in patients with radial fracture. Auton Neurosci. 2000 Dec 28;86(1-2):127-34.
Geertzen JH, Dijkstra PU, Groothoff JW, ten Duis HJ, Eisma WH. Reflex sympathetic dystrophy of the upper extremity--a 5.5-year follow-up. Part I. Impairments and perceived disability. Acta Orthop Scand Suppl. 1998 Apr;279:12-8.
Puchalski P, Zyluk A. Complex regional pain syndrome type 1 after fractures of the distal radius: a prospective study of the role of psychological factors. J Hand Surg Br. 2005 Dec;30(6):574-80.
Rewhorn MJ, Leung AH, Gillespie A, Moir JS, Miller R. Incidence of complex regional pain syndrome after foot and ankle surgery. J Foot Ankle Surg. 2014 May-Jun;53(3):256-8. [
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 Mar;95(3):487-92.
Ratti C, Nordio A, Resmini G, Murena L. Post-traumatic complex regional pain syndrome: clinical features and epidemiology. Clin Cases Miner Bone Metab. 2015 Jan-Apr;12(Suppl 1):11-6.
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 May;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 May;129(1-2):12-20.
de Mos M, Huygen FJPM, Stricker CBH, Dieleman JP, Sturkenboom MCJM. The association between ACE inhibitors and the complex regional pain syndrome: Suggestions for a neuro-inflammatory pathogenesis of CRPS. Pain. 2009 Apr;142(3):218-224.
An HS, Hawthorne KB, Jackson WT. Reflex sympathetic dystrophy and cigarette smoking. J Hand Surg Am. 1988 May;13(3):458-60.
Goh EL, Chidambaram S, Ma D. Complex regional pain syndrome: a recent update. Burns Trauma. 2017;5:2.
Huygen FJ, De Bruijn AG, De Bruin MT, Groeneweg JG, Klein J, Zijlstra FJ. Evidence for local inflammation in complex regional pain syndrome type 1. Mediators Inflamm. 2002 Feb;11(1):47-51.
Alexander GM, van Rijn MA, van Hilten JJ, Perreault MJ, Schwartzman RJ. Changes in cerebrospinal fluid levels of pro-inflammatory cytokines in CRPS. Pain. 2005 Aug;116(3):213-219.
Uçeyler N, Eberle T, Rolke R, Birklein F, Sommer C. Differential expression patterns of cytokines in complex regional pain syndrome. Pain. 2007 Nov;132(1-2):195-205.
Parkitny L, McAuley JH, Di Pietro F, Stanton TR, O'Connell NE, Marinus J, van Hilten JJ, Moseley GL. Inflammation in complex regional pain syndrome: a systematic review and meta-analysis. Neurology. 2013 Jan 01;80(1):106-17.
Leis S, Weber M, Schmelz M, Birklein F. Facilitated neurogenic inflammation in unaffected limbs of patients with complex regional pain syndrome. Neurosci Lett. 2004 Apr 15;359(3):163-6.
Birklein F, Schmelz M, Schifter S, Weber M. The important role of neuropeptides in complex regional pain syndrome. Neurology. 2001 Dec 26;57(12):2179-84.
Schinkel C, Gaertner A, Zaspel J, Zedler S, Faist E, Schuermann M. Inflammatory mediators are altered in the acute phase of posttraumatic complex regional pain syndrome. Clin J Pain. 2006 Mar-Apr;22(3):235-9.
Birklein F, Schmelz M. Neuropeptides, neurogenic inflammation and complex regional pain syndrome (CRPS). Neurosci Lett. 2008 Jun 06;437(3):199-202.
Kohr D, Singh P, Tschernatsch M, Kaps M, Pouokam E, Diener M, Kummer W, Birklein F, Vincent A, Goebel A, Wallukat G, Blaes F. Autoimmunity against the β2 adrenergic receptor and muscarinic-2 receptor in complex regional pain syndrome. Pain. 2011 Dec;152(12):2690-2700.
Dubuis E, Thompson V, Leite MI, Blaes F, Maihöfner C, Greensmith D, Vincent A, Shenker N, Kuttikat A, Leuwer M, Goebel A. Longstanding complex regional pain syndrome is associated with activating autoantibodies against alpha-1a adrenoceptors. Pain. 2014 Nov;155(11):2408-17.
Goebel A, Baranowski A, Maurer K, Ghiai A, McCabe C, Ambler G. Intravenous immunoglobulin treatment of the complex regional pain syndrome: a randomized trial. Ann Intern Med. 2010 Feb 02;152(3):152-8.
Sigtermans MJ, van Hilten JJ, Bauer MCR, Arbous SM, Marinus J, Sarton EY, Dahan A. Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1. Pain. 2009 Oct;145(3):304-311.
Schwartzman RJ, Alexander GM, Grothusen JR, Paylor T, Reichenberger E, Perreault M. Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study. Pain. 2009 Dec 15;147(1-3):107-15.
Maihöfner C, Handwerker HO, Neundörfer B, Birklein F. Patterns of cortical reorganization in complex regional pain syndrome. Neurology. 2003 Dec 23;61(12):1707-15.
Maihöfner C, Handwerker HO, Neundörfer B, Birklein F. Cortical reorganization during recovery from complex regional pain syndrome. Neurology. 2004 Aug 24;63(4):693-701.
Pleger B, Tegenthoff M, Ragert P, Förster AF, Dinse HR, Schwenkreis P, Nicolas V, Maier C. Sensorimotor retuning [corrected] in complex regional pain syndrome parallels pain reduction. Ann Neurol. 2005 Mar;57(3):425-9.
Misidou C, Papagoras C. Complex Regional Pain Syndrome: An update. Mediterr J Rheumatol. 2019 Mar;30(1):16-25.
Terkelsen AJ, Mølgaard H, Hansen J, Finnerup NB, Krøner K, Jensen TS. Heart rate variability in complex regional pain syndrome during rest and mental and orthostatic stress. Anesthesiology. 2012 Jan;116(1):133-46.
Halicka M, Vittersø AD, Proulx MJ, Bultitude JH. Neuropsychological Changes in Complex Regional Pain Syndrome (CRPS). Behav Neurol. 2020;2020:4561831.
Libon DJ, Schwartzman RJ, Eppig J, Wambach D, Brahin E, Peterlin BL, Alexander G, Kalanuria A. Neuropsychological deficits associated with Complex Regional Pain Syndrome. J Int Neuropsychol Soc. 2010 May;16(3):566-73.
Park JY, Ahn RS. Hypothalamic-pituitary-adrenal axis function in patients with complex regional pain syndrome type 1. Psychoneuroendocrinology. 2012 Sep;37(9):1557-68.
Irwin DJ, Schwartzman RJ. Complex regional pain syndrome with associated chest wall dystonia: a case report. J Brachial Plex Peripher Nerve Inj. 2011 Sep 26;6:6.
Schwartzman RJ, Erwin KL, Alexander GM. The natural history of complex regional pain syndrome. Clin J Pain. 2009 May;25(4):273-80.
Chancellor MB, Shenot PJ, Rivas DA, Mandel S, Schwartzman RJ. Urological symptomatology in patients with reflex sympathetic dystrophy. J Urol. 1996 Feb;155(2):634-7.
Lee JW, Lee SK, Choy WS. Complex Regional Pain Syndrome Type 1: Diagnosis and Management. J Hand Surg Asian Pac Vol. 2018 Mar;23(1):1-10.
Nijs J, Kosek E, Van Oosterwijck J, Meeus M. Dysfunctional endogenous analgesia during exercise in patients with chronic pain: to exercise or not to exercise? Pain Physician. 2012 Jul;15(3 Suppl):ES205-13.
Moseley GL, Flor H. Targeting cortical representations in the treatment of chronic pain: a review. Neurorehabil Neural Repair. 2012 Jul-Aug;26(6):646-52.
Smart KM, Ferraro MC, 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. 2022 May 17;5(5):CD010853.
O'Connell NE, Wand BM, McAuley J, Marston L, Moseley GL. Interventions for treating pain and disability in adults with complex regional pain syndrome. Cochrane Database Syst Rev. 2013 Apr 30;2013(4):CD009416.
Kalita J, Vajpayee A, Misra UK. Comparison of prednisolone with piroxicam in complex regional pain syndrome following stroke: a randomized controlled trial. QJM. 2006 Feb;99(2):89-95.
Kalita J, Misra U, Kumar A, Bhoi SK. Long-term Prednisolone in Post-stroke Complex Regional Pain Syndrome. Pain Physician. 2016 Nov-Dec;19(8):565-574.
Harden RN, McCabe CS, Goebel A, Massey M, Suvar T, Grieve S, Bruehl S. Complex Regional Pain Syndrome: Practical Diagnostic and Treatment Guidelines, 5th Edition. Pain Med. 2022 Jun 10;23(Suppl 1):S1-S53.
Varenna M, Adami S, Sinigaglia L. Bisphosphonates in Complex Regional Pain syndrome type I: how do they work? Clin Exp Rheumatol. 2014 Jul-Aug;32(4):451-4.
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. Joint Bone Spine. 2017 Jul;84(4):393-399.
Brown S, Johnston B, Amaria K, Watkins J, Campbell F, Pehora C, McGrath P. A randomized controlled trial of amitriptyline versus gabapentin for complex regional pain syndrome type I and neuropathic pain in children. Scand J Pain. 2016 Oct;13:156-163.
Zhu H, Wen B, Xu J, Zhang Y, Xu L, Huang Y. Efficacy and Safety of Pharmacological Treatment in Patients with Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis. Pharmaceuticals (Basel). 2024 Jun 20;17(6)
Kaye AD, Nguyen A, Boullion J, Blue MF, Allen DWH, Kelkar RA, Mouhaffel A, Ro AT, Ahmadzadeh S, Shekoohi S, Robinson CL. Efficacy of Immunotherapy for Complex Regional Pain Syndrome: A Narrative Review. Curr Pain Headache Rep. 2025 Jan 04;29(1):4.
Harden RN, Oaklander AL, Burton AW, Perez RS, Richardson K, Swan M, Barthel J, Costa B, Graciosa JR, Bruehl S., Reflex Sympathetic Dystrophy Syndrome Association. Complex regional pain syndrome: practical diagnostic and treatment guidelines, 4th edition. Pain Med. 2013 Feb;14(2):180-229.
O'Connell NE, Wand BM, Gibson W, Carr DB, Birklein F, Stanton TR. Local anaesthetic sympathetic blockade for complex regional pain syndrome. Cochrane Database Syst Rev. 2016 Jul 28;7(7):CD004598.
Huygen FJPM, Kallewaard JW, Nijhuis H, Liem L, Vesper J, Fahey ME, Blomme B, Morgalla MH, Deer TR, Capobianco RA. Effectiveness and Safety of Dorsal Root Ganglion Stimulation for the Treatment of Chronic Pain: A Pooled Analysis. Neuromodulation. 2020 Feb;23(2):213-221.
Deer TR, Levy RM, Kramer J, Poree L, Amirdelfan K, Grigsby E, Staats P, Burton AW, Burgher AH, Obray J, Scowcroft J, Golovac S, Kapural L, Paicius R, Kim C, Pope J, Yearwood T, Samuel S, McRoberts WP, Cassim H, Netherton M, Miller N, Schaufele M, Tavel E, Davis T, Davis K, Johnson L, Mekhail N. Dorsal root ganglion stimulation yielded higher treatment success rate for complex regional pain syndrome and causalgia at 3 and 12 months: a randomized comparative trial. Pain. 2017 Apr;158(4):669-681.
Zalewski A, Andreieva I, Wiśniowska J, Tarnacka B, Gromadzka G. Clinical and Molecular Barriers to Understanding the Pathogenesis, Diagnosis, and Treatment of Complex Regional Pain Syndrome (CRPS). Int J Mol Sci. 2025 Mar 11;26(6)
Bruehl S, Harden RN, Galer BS, Saltz S, Backonja M, Stanton-Hicks M. Complex regional pain syndrome: are there distinct subtypes and sequential stages of the syndrome? Pain. 2002 Jan;95(1-2):119-24.
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 Aug;29(8):e235-41.
Aïm F, Klouche S, Frison A, Bauer T, Hardy P. Efficacy of vitamin C in preventing complex regional pain syndrome after wrist fracture: A systematic review and meta-analysis. Orthop Traumatol Surg Res. 2017 May;103(3):465-470.
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