Opinion statement
Complex regional pain syndrome (CRPS) is a heterogeneous disorder that falls in the spectrum of neuropathic pain disorders. It is maintained by abnormalities throughout the neuraxis (the peripheral, autonomic, and central nervous systems). The pathophysiology of CRPS is not fully known. There are no scientifically well-established treatments. The diagnostic criteria for CRPS at this time are purely clinical, and the use of diagnostic tests has not been demonstrated. The most appropriate management of CRPS uses a multidisciplinary approach, with the inclusion of medical and psychologic intervention, and physical and occupational therapy. The key is gradual, persistent, functional improvement. The rational use of pain therapies must be grounded in a thorough knowledge of the neurobiology of pain, its endogenous modulation, and the clinical presentation. Potential peripheral pathophysiologic targets (and possible treatments) include increased spontaneous firing and responsiveness of peripheral afferent fibers mediated by inflammatory and other algogenic substances (somatosensory blocks, corticosteroids), altered levels of expression and functioning of multiple ion channels (local anesthetics, calcium channel blockers, anticonvulsants), abnormal interneuronal communication, and increased peripheral expression of adrenergic receptors and sympathetic excitation (sympathetic blocks, alpha-adrenergic antagonists, alpha-2 agonists). CRPS is also perpetuated by central mechanisms, with pathophysiologic targets (and possible treatments) including reorientation of dorsal horn terminals (desensitization techniques), functional reduction in inhibitory interneuron activity (tricyclic antidepressants, gabapentin, opioids), central sensitization and increased central excitability (gabapentin, topiramate, spinal cord stimulation, somatosensory blocks), impaired descending nociceptive inhibition (tricyclic antidepressants, opioids), and adaptive changes in the cortical centers underlying the sensory-discriminative and affective-motivational dimensions of pain (psychologic, physical, and occupational therapies). The treatment choices should be aimed at remodulating, normalizing, disrupting, or preventing the progression of abnormalities in pain processing. Sympathetic nerve blocks should be performed at least once to assess if sympathetically maintained pain is present. To the extent that peripheral somatosensory nerve blocks can diminish nociceptive input to the central nervous system, these techniques may help reduce the nociceptive sensitization of spinal neurons. Pain relief, however it is achieved and however temporary it is, is intended to facilitate participation in functional therapies to normalize use and to improve motion, strength, and dexterity. Psychologic therapies, such as biofeedback and cognitive-behavioral techniques targeting pain, stress, and mood disorders, are valuable adjunctive treatments for pain control and can facilitate functional improvement.
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References and Recommended Reading
Birklein F, Riedl B, Claus D, Neudorfer B: Pattern of autonomic dysfunction in time course of complex regional pain syndrome. Clin Auton Res 1998, 8:79–85.
Kurvers H, Daemen M, Slaaf D, et al.: Partial peripheral neuropathy and denervation induced adrenoceptor supersensitivity. ACTA Orthop Belg 1998, 64:64–70.
Jänig W, Baron R: The role of the sympathetic nervous system in neuropathic pain: clinical observations and animal models. In Neuropathic Pain: Pathophysiology and Treatment. Edited by Hansson PT, Fields HL, Hill RG, Marchettini P. Seattle: IASP Press; 2001. This chapter presents a current overview by leading researchers of what is known regarding the sympathetic nervous system in neuropathic pain conditions.
Gracely RH, Lynch SA, Bennett GJ: Painful neuropathy: altered central processing maintained dynamically by peripheral input. Pain 1992, 51:175–194.
Merskey H, Bogduk N. Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. Seattle: IASP Press; 1994.
Bruehl S, Harden RN, Galer BS, et al.: External validation of IASP diagnostic criteria for complex regional pain syndrome and proposed research diagnostic criteria. Pain 1999, 81:147–154.
Stanton-Hicks M, Baron R, Boas R, et al.: Complex regional pain syndromes: guidelines for therapy. Clin J Pain 1998, 14:155–166.
Stanton-Hicks MD, Burton AW, Bruehl SP, et al.: An updated interdisciplinary clinical pathway for CRPS: report of an expert panel. Pain Pract 2002, 2:1–16. This article overviews the treatment recommendations of an expert panel of leading CRPS clinicians and researchers, and describes issues related to treatment sequencing and integration of multidisciplinary treatments.
Christensen K, Jensen EM, Noer I: The reflex dystrophy syndrome response to treatment with systemic corticosteroids. Acta Chir Scand 1982, 148:653–655.
Braus DF, Krauss JK, Strobel J: The shoulder-hand syndrome after stroke: a prospective clinical trial. Ann Neurol 1994, 36:728–733.
Sindrup SH, Jensen ST. Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action. Pain 1999, 83:389–400.
McQuay HJ, Tramer M, Nye BA, et al.: A systematic review of antidepressants in neuropathic pain. Pain 1996, 68:217–227.
Collins SL, Moore RA, McQuay HJ, Wiffen P: Antidepressants and anticonvulsants for diabetic neuropathy and postherpetic neuralgia: a quantitative systematic review. J Pain Symptom Manage 2000, 20:449–458.
Wiffen P, Collins S, McQuay H, et al.: Anticonvulsant drugs for acute and chronic pain. Cochrane Database Sys Rev 2000, 3:CD001133.
Harke H, Gretenkort P, Ladleif HU, et al.: The response of neuropathic pain and pain in complex regional pain syndrome I to carbamazepine and sustainedrelease morphine in patients pretreated with spinalcord stimulation: a double-blinded randomized study. Anesth Anal 2001, 92:488–495.
Mellick GA, Mellick LB: Reflex sympathetic dystrophy treated with gabapentin. Arch Phys Med Rehabil 1997, 78:98–105.
Muizelaar JP, Kleyer M, Hertogs IAM, Delange DC. Complex regional syndrome (reflex sympathetic dystrophy and causalgia): management with the calcium channel blocker nifedipine and/or the alpha sympathetic blocker phenoxybenzamine in 59 patients. Clin Neur Neurosurgery 1997, 99:26–30.
Ghostine SY, Comair YG, Turner DM, et al.: Phenoxybenzamine in the treatment of causalgia: report of 40 cases. J Neurosurg 1984, 60:1263–1268.
Davis KD, Treede RD, Raja SN, et al.: Topical application of clonidine relieves hyperalgesia in patients with sympathetically maintained pain. Pain 1991, 47:309–317.
Byas-Smith MG, Max MB, Muir J, Kingman A. Transdermal clonidine compared to placebo in painful diabetic neuropathy using a two-stage ‘enriched enrollment’ design. Pain 1995, 60:267–274.
Watson CP, Babul N: Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia. Neurology 1998, 50:1837–1841.
Dellemijn PL, Van Duijn H, Vanneste JA: Prolonged treatment with transdermal fentanyl in neuropathic pain. J Pain Symptom Manage 1998, 16:220–229.
Cherny NI, Thaler HT, Klar HF, et al.: Opioid responsiveness of cancer pain syndromes caused by neuropathic or nociceptive mechanisms: a combined analysis of controlled, single dose studies. Neurology 1994, 44:857–861.
Portenoy RK, Foley KM, Inturrisi CE: The nature of opioid responsiveness and its implications for neuropathic pain: new hypothesis derived from studies of opioid infusions. Pain 1990, 43:273–286.
Dellemijn P: Are Opioids effective in relieving neuropathic pain? Pain 1999, 80:453–462.
Braga PC: Calcitonin and its antinociceptive activity: animal and human investigations. Agents Actions 1994, 41:121–131.
Perez RSGM, Kwakkel G, Zuurmond WWA, de Lange JJ: Treatment of reflex sympathetic dystrophy (CRPS type I): a research synthesis of 21 randomized clinical trials. J Pain Symptom Manage 2001, 21:511–526. This is the only available meta-analysis specifically of CRPS treatments, and should be referred to for additional information on clinical trials that have reported negative results for treatments mentioned in the current article.
Gobelet C, Waldburger M, Meier JL: The effect of adding calcitonin to physical treatment on reflex sympathetic dystrophy. Pain 1992, 48:171–175.
Cherot A, Amor B. Treatment of algodystrophy. A randomized study of 95 cases with 3 treatments: Calsyn 100, Visken, Grisefuline and Penthonium. Rev Rhum Mal Osteoartic 1983, 50:95–97
Friez L, Pere G, Breuillard P, Meignan S: Comparison of treatment with griseofulvin, beta blockers and calcitonin in 55 cases of post-traumatic algoneurodystrophies. Rev Rhum Mal Osteoartic 1982, 49:857–860.
Appelboom T: Calcitonin in reflex sympathetic dystrophy syndrome and other painful conditions. Bone 2002, 30(suppl):84S-86S.
Bickerstaff DR, Kanis JA: The use of nasal calcitonin in the treatment of post-traumatic algodystrophy. Br J Rheumatol 1991, 30:291–294.
Geertzen JH, de Bruijn H, de Bruijn-Kofman AT, Arendzen JH: Reflex sympathetic dystrophy: early treatment and psychological aspects. Arch Phys Med Rehabil 1994, 75:442–446.
Prough DS, McLeskey CH, Poehling GG, et al.: Efficacy of oral nifedipine in the treatment of reflex sympathetic dystrophy. Anesthesiology 1985, 62:796–799.
Adami S, Fossaluzza V, Gatti D, et al.: Bisphosphonate therapy of reflex sympathetic dystrophy syndrome. Ann Rheum Dis 1997, 56:201–204.
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.
Kubalek I, Fain O, Paries J, et al.: Treatment of reflex sympathetic dystrophy with pamidronate: 29 cases. Br Soc Rheum 2001, 40:1394–1397.
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.
Price DD, Long S, Wilsey B, Rafii A: Analysis of peak magnitude and duration of analgesia produced by local anesthetics injected into sympathetic ganglia of complex regional pain syndrome patients. Clin J Pain 1998, 14:216–226.
Cepeda MS, Lau J, Carr DB: Defining the therapeutic role of local anesthetic sympathetic blockade in complex regional pain syndrome: a narrative and systematic review. Clin J Pain 2002, 18:216–233.
Dellemijn Pl, Fields HL, Allen RR, et al.: The interpretation of pain relief and sensory changes following sympathetic blockade. Brain 1994, 117:1475–1487.
Schurmann M, Gradl G, Wizgal I, et al.: Clinical and physiological evaluation of stellate ganglion blockade for complex regional pain syndrome type I. Clin J Pain 2001, 17:194–200.
Ramamurthy S, Hoffman J: Intravenous regional guanethidine in the treatment of reflex sympathetic dystrophy/ causalgia: a randomized, double blind study. Guanethidine study group. Anesth Analg 1995, 81:718–723.
Glynn CJ, Basedow RW, Walsh JA: Pain relief following post-ganglionic sympathetic blockade with IV guanethidine. Br J Anesth 1981, 53:1297–1302.
Tramer MR, Glynn CJ: Magnesium Bier’s block for treatment of chronic limb pain: a randomized, double-blind, cross-over study. Pain 2002, 99:235–241.
Bonelli S, Conoscente F, Movilia PG, et al.: Regional intravenous guanethidine vs stellate ganglion block in reflex sympathetic dystrophies: a randomized trial. Pain 1983, 16:297–307.
Glynn CJ, Basedow RW, Walsh JA: Pain relief following post-ganglionic sympathetic blockade with IV guanethidine. Br J Anaesth 1981, 53:1297–1301.
Jadad AR, Carroll D, Glynn CJ, McQuay HJ: Intravenous regional sympathetic blockade for pain relief in reflex sympathetic dystrophy: a systematic review and a randomized, double-blind crossover study. J Pain Symptom Manage 1995, 10:13–20.
Hord AH, Rooks MD, Stephens BO, et al.: Intravenous regional bretylium and lidocaine for treatment of reflex sympathetic dystrophy: a randomized, doubleblind study. Anesth Analg 1992, 74:818–821.
Hanna MH, Peat SJ: Ketanserin in reflex sympathetic dystrophy: a double-blind placebo-controlled crossover trial. Pain 1989, 38:145–150.
Reuben SS, Sklar J: Intravenous regional anesthesia with clonidine in the management of complex regional pain syndrome of the knee. J Clin Anesth 2002, 14:87–91.
Ribbers GM, Geurts AC, Rijken RA, Kerkkamp HE: Axillary brachial plexus blockade for the reflex sympathetic dystrophy syndrome. Int J Rehabil Res 1997, 20:371–380.
Gibbons JJ, Wilson PR, Lamer TJ, Elliot BA: Interscalene blocks for chronic upper extremity pain. Clin J Pain 1992, 8:264–269.
Klein DS, Klein PW: Low-volume ulnar nerve block within axillary sheath for the treatment of reflex sympathetic dystrophy. Can J Anesth 1991, 38:764–766.
Azad SC, Beyer A, Romert AW, et al.: Continuous axillary brachial plexus analgesia with low-dose morphine in patients with complex regional pain syndromes. Euro J Anest 2000, 17:185–188.
Murray P, Atkinson RE: Continuous axillary brachial plexus blockade for reflex sympathetic dystrophy. Anaesthesia 1995, 50:633–635.
Margic K, Pirc J: The treatment of complex regional pain syndrome (CRPS) involving upper extremity with continuous sensory analgesia. Eur J Pain 2003, 7:43–47.
Wechsler RJ, Frank ED, Halpern EH, et al.: Percutaneous lumbar sympathetic plexus catheter placement for short- and long-term pain relief: CT technique and results. J Comput Assist Tomogr 1998, 22:518–523.
Lin TC, Wong CS, Chen FC, et al.: Long-term epidural ketamine, morphine and bupivacaine attenuate reflex sympathetic dystrophy neuralgia. Can J Anesth 1998, 45:175–177.
Rauck RL, Eisenach JC, Jackson K, et al.: Epidural clonidine treatment for refractory reflex sympathetic dystrophy. Anesthesiology 1993, 79:1163–1169.
Kemler MA, Barendse GA, Van Kleef M, et al.: Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy. N Eng J Med 2000, 343:618–624.
Kemler MA, Berendise GAM, Kleef MV, et al.: Electrical spinal cord stimulation in reflex sympathetic dystrophy: retrospective analysis of 23 patients. J Neurosurg 1999, 90:79–83.
Kemler MA, Reulen PHJ, Barendse AMG, et al.: Impact of spinal cord stimulation on sensory characteristics in complex regional pain syndrome type I. Anesthesiology 2001, 95:72–80.
Sandroni P, Benrud-Larson LM, McClelland RL, Low PA: Complex regional pain syndrome type I: incidence and prevalence in Olmsted County, a populationbased study. Pain 2003, in press.
Carlson LK, Watson HK: Treatment of reflex sympathetic dystrophy using the stress-loading program. J Hand Ther 1988, 5:149–153.
Oerlemans HM, Oostendorp RAB, de Boo T, Goris RJA: Pain and reduced mobility in complex regional pain syndrome I: outcome of a prospective randomized controlled clinical trial of adjuvant physical therapy versus occupational therapy. Pain 1999, 83:77–83.
Lee BH, Scharff L, Sethna NF, et al.: Physical therapy and cognitive-behavioral treatment for complex regional pain syndromes. J Pediatr 2002, 141:135–140.
Sherry DD, Wallace CA, Kelley C, et al.: Short- and longterm outcomes of children with complex regional pain syndrome type I treated with exercise therapy. Clin J Pain 1999, 15:218–223.
Feldman SI, Downey G, Schaffer-Neitz R: Pain, negative mood, and perceived social support in chronic pain patients: a daily diary study of people with reflex sympathetic dystrophy syndrome. J Consult Clin Psy 1999, 67:776–785.
Barowsky EI, Zweig JB, Moskowitz J: Thermal biofeedback in the treatment of symptoms associated with reflex sympathetic dystrophy. J Child Neurol 1987, 2:229–232.
Morley S, Eccleston C, Williams A: Systematic review and meta-analysis of randomized controlled trials of cognitive behavior therapy and behavior therapy for chronic pain in adults, excluding headache. Pain 1999, 80:1–13.
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Chung, O.Y., Bruehl, S.P. Complex regional pain syndrome. Curr Treat Options Neurol 5, 499–511 (2003). https://doi.org/10.1007/s11940-996-0018-6
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DOI: https://doi.org/10.1007/s11940-996-0018-6