Abstract
Complex regional pain syndrome is a neuroinflammatory condition associated with overactive glial cells that can be challenging to diagnose and treat. Early recognition and treatment are thought to be critical for good outcomes, yet many patients experience a delay in diagnosis and have difficulty accessing expert medical care. While there are no universally effective treatments, there are several promising new therapies, but these are not widely available. Some of the specific barriers to diagnosis and treatment are reviewed, with suggestions as to how they might be eliminated, leading to better care for all patients with CRPS.
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References
Ballow M (2011) The IgG molecule as a biological immune response modifier: mechanisms of action of intravenous immune serum globulin in autoimmune and inflammatory disorders. J Allergy Clin Immunol 127(2):315–323
Bernateck M, Karst M, Gratz KF, Meyer GJ, Fischer MJ, Knapp WH, Koppert W, Brunkhorst T (2010) The first scintigraphic detection of tumor necrosis factor-alpha in patients with complex regional pain syndrome type. Anesth Analg 110(1):211–215
Bianchi C, Rossi S, Turi S, Brambilla A, Felisari G, Mascheri D (2006) Long-term functional outcome measures in corticosteroid-treated complex regional pain syndrome. Eura Medicophys 42(2):103–111
Cappello ZJ, Kasdan ML, Louis DS (2012) Meta-analysis of the imaging techniques for the diagnosis of complex regional pain syndrome Type I. J Hand Surg Am 37(2):288–296
De Bosscher K (2010) Selective glucocorticoid receptor modulators. J Steroid Biochem Mol Biol 120:96–104
Goebel A (2010) Immunoglobulin responsive chronic pain. J Clin Immunol 30(Suppl 1):S103–S108
Goebel A, Baranowski A, Maurer K, Ghiai A, McCabe C, Ambler G (2010) Intravenous immunoglobulin treatment of the complex regional pain syndrome: a randomized trial. Ann Intern Med 152(3):152–158
Goldberg ME, Domsky R, Scaringe D, Hirsh R, Dotson J, Sharaf I, Torjman MC, Schwartzman RJ (2005) Multi-day low dose ketamine infusion for the treatment of complex regional pain syndrome. Pain Physician 8(2):175–179
Goldberg ME, Torjman MC, Schwartzman RJ, Mager DE, Wainer IW (2010) Pharmacodynamic profiles of ketamine (R)- and (S)- with 5-day inpatient infusion for the treatment of complex regional pain syndrome. Pain Physician 13(4):379–387
Harden RN (ed) (2006) Complex regional pain syndrome: treatment guidelines. RSDSA Press, Milford CT
Hocking G, Cousins MJ (2003) Ketamine in chronic pain management: an evidence based review. Anesth Analg 97:1730–1739
Hutchinson MR, Zhang Y, Brown K, Coats BD, Shridhar M, Sholar PW, Patel SJ, Crysdale NY, Harrison JA, Maier SF, Rice KC, Watkins LR (2008) Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4). Eur J Neurosci 28(1):20–29
Huygen FJ, Niehof S, Zijlstra FJ, van Hagen PM, van Daele PL (2004) Successful treatment of CRPS 1 with anti-TNF. J Pain Symptom Manage 27(2):101–103
Inchiosa MA Jr, Kizelshteyn G (2008) Treatment of complex regional pain syndrome type I with oral phenoxybenzamine: rationale and case reports. Pain Pract 8(2):125–132
Ingelfinger JR, Drazen JM (2011) Patient organizations and research on rare diseases. N Engl J Med 364:1670–1671
Jensen MP, Gammaitoni AR, Bolognese JA, Alon A, Smugar SS, Galer BS, Hewitt DJ (2011 Dec 7) The pain quality response profile of pregabalin in the treatment of neuropathic pain. Clin J Pain. [Epub ahead of print]
Kiefer RT, Rohr P, Ploppa A, Dieterich HJ, Grothusen J, Koffler S, Altemeyer KH, Unertl K, Schwartzman RJ (2008) Efficacy of ketamine in anesthetic dosage for the treatment of refractory complex regional pain syndrome: an open-label phase II study. Pain Med 9(8):1173–1201
Kohr D, Singh P, Tschernatsch M, Kaps M, Pouokam E, Diener M, Kummer W, Birklein F, Vincent A, Goebel A, Wallukat G, Blaes F (2011) Autoimmunity against the β(2) adrenergic receptor and muscarinic-2 receptor in complex regional pain syndrome. Pain 152(12):2690–2700
Kozin F, Ryan LM, Carerra GF, Soin JS, Wortmann RL (1981) The reflex sympathetic dystrophy syndrome (RSDS). III. Scintigraphic studies, further evidence for the therapeutic efficacy of systemic corticosteroids, and proposed diagnostic criteria. Am J Med 70(1):23–30
Legge J, Ball N, Elliot DP (2006) The potential role of ketamine in hospice analgesia: a literature review. Consult Pharm 21:51–57
Maihöfner C, Seifert F, Markovic K (2010) Complex regional pain syndromes: new pathophysiological concepts and therapies. Eur J Neurol 17(5):649–660
McCabe CS, Haigh RC, Blake DR (2008) Mirror visual feedback for the treatment of complex regional pain syndrome (type 1). Curr Pain Headache Rep 12(2):103–107
Netherlands Society of Rehabilitation Specialists, Netherlands Society of Anaesthesiologists. Complex regional pain syndrome type I guidelines, 2006. (Available online http://www.rsds.org/clinical_guidelines.html)
Perez RS, Zuurmond WW, Bezemer PD, Kuik DJ, van Loenen AC, de Lange JJ, Zuidhof AJ (2003) The treatment of complex regional pain syndrome type I with free radical scavengers: a randomized controlled study. Pain 102(3):297–307
Ribbers GM, Stam HJ (2001) Complex regional pain syndrome type I treated with topical capsaicin: a case report. Arch Phys Med Rehabil 82(6):851–852
Schwartzman RJ, Alexander GM, Grothusen JR, Paylor T, Reichenberger E, Perreault M (2009) Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study. Pain 147(1–3):107–115
Sinis N, Birbaumer N, Schwarz A, Gustin S, Unertl K, Schaller HE, Haerle M (2006) Memantine and Complex Regional Pain Syndrome (CRPS): effects of treatment and cortical reorganisation. Handchir Mikrochir Plast Chir 38(3):164–171
Sinis N, Birbaumer N, Gustin S, Schwarz A, Bredanger S, Becker ST, Unertl K, Schaller HE, Haerle M (2007) Memantine treatment of complex regional pain syndrome: a preliminary report of six cases. Clin J Pain 23(3):237–243
Soderquist RG, Sloane EM, Loram LC, Harrison JA, Dengler EC, Johnson SM, Amer LD, Young CS, Lewis MT, Poole S, Frank MG, Watkins LR, Milligan ED, Mahoney MJ (2010) Release of plasmid DNA-encoding IL-10 from PLGA microparticles facilitates long-term reversal of neuropathic pain following a single intrathecal administration. Pharm Res 27(5):841–857
van Rijn MA, Marinus J, Putter H, Bosselaar SR, Moseley GL, van Hilten JJ (2011) Spreading of complex regional pain syndrome: not a random process. J Neural Transm 118(9):1301–1309
Villanueva-Perez VL, Cerdá-Olmedo G, Samper JM, Mínguez A, Monsalve V, Bayona MJ, De Andrés JA (2007) Oral ketamine for the treatment of type I complex regional pain syndrome. Pain Pract 7(1):39–43
Zollinger PE, Tuinebreijer WE, Breederveld RS, Kreis RW (2007) 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 89(7):1424–1431
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Binkley, K.E. Improving the Diagnosis and Treatment of CRPS: Insights from a Clinical Immunologist’s Personal Experience with an Underrecognized Neuroinflammatory Disorder. J Neuroimmune Pharmacol 8, 477–488 (2013). https://doi.org/10.1007/s11481-012-9376-x
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DOI: https://doi.org/10.1007/s11481-012-9376-x