J Korean Med Assoc.  2008 Jun;51(6):553-568. 10.5124/jkma.2008.51.6.553.

Complex Regional Pain Syndrome: Mechanism, Diagnosis and Treatment

• Kim C

• KMID: 1481928
• DOI: http://doi.org/10.5124/jkma.2008.51.6.553

Abstract

Complex regional pain syndromes (CRPS, formerly reflex sympathetic dystrophy and causalgia) are neuropathic pain disorders of one or more extremities developing inadequately after traumas or lesions in the peripheral or central nervous system (CNS). However, CPRS may also develop spontaneously. CRPS is clinically characterized by sensory (pain, hyperalgesia, and allodynia), autonomic (disturbances of skin temperature, color change, and presence of sweating abnormalities), and motor (paresis, tremor, and dystonia) disturbances. There have been growing evidences for that CRPS is a systemic disease involving the CNS and peripheral nervous system. The diagnosis is mainly based on clinical symptoms and signs, so that it could be under- or over-diagnosed. However, careful clinical evaluation and additional tests should lead to an adequate diagnosis. The goal of treatment is to improve functions, relieve pain, and achieve remission. The early diagnosis and multidisciplinary treatments, which include pain management, rehabilitation, and psychological therapy, are the most important elements for solving the patients' problems.

Keyword

Complex regional pain syndrome; Neuropathic pain; Central nervous system

MeSH Terms

Cardiopulmonary Resuscitation
Central Nervous System
Early Diagnosis
Extremities
Hyperalgesia
Neuralgia
Pain Management
Peripheral Nervous System
Reflex Sympathetic Dystrophy
Skin Temperature
Sweat
Sweating
Tremor

Figure

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  Figure 1 A CRPS patient with 7 months of pain duration. The patient suffered from the right leg pain, especially, below the ankle after the right knee contusion and arthroscopy.

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  Figure 2 A CRPS patient with 8 months pain duration. Left foot shows reddish and swelling. Sweat drops are seen around the left great toe and right foot shows no sweating.

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  Figure 3 A CRPS patient with 4 months of pain duration. The patient developed CRPS of the right upper extremity after the right wrist sprain followed by falling down. Right hand shows severe swelling.

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  Figure 4 Possible couplings between sympathetic neurons and afferent neurons. Coupling with primary afferent neurons depends on activity in the sympathetic neurons and the expression of functional adrenoceptors by the afferent neurons, or is mediated indirectly via the blood vessels (blood flow). It can occur in the periphery, in the dorsal root ganglion, or, possibly, in the lesioned nerve (A). The inflammatory mediator bradykinin (BK) reacts with B2 receptors in the membrane of the sympathetic varicosities, inducing release of prostaglandin E2 (PGE2; B). Nerve growth factor (NGF) released during inflammation reacts with the high-affinity receptor trkA for NGF in the membrane of the sympathetic varicosities, inducing release of an inflammatory mediator or inflammatory mediators (C). Activation of the adrenal medulla (AM) by sympathetic preganglionic neurons leads to release of a hormone (possibly adrenaline) (D). (adopted from Janig w 2000).

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  Figure 5 Modes of neural plasticity at synapses onto nociceptive transmission neurons in the dorsal horn of the spinal cord. The neurons are activated by fast EPSPs and enhanced by slow EPSPs, plateau potentials, and windup. Modulation through intracellular kinase/phosphatase signaling cascades produces central sensitization through facilitating AMPA/kainate and NMDA receptor function or cell-surface expression. Modification is mediated by induced expression of gene products, loss of inhibitory interneurons, and establishment of aberrant excitatory synaptic connections (adopted from Woolf CJ 2003).

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  Figure 6 Schematic diagram of sensory, autonomic, and somatomotor changes in patients with CRPS I. Changes are triggered and possibly maintained by the nociceptive afferent input from the somatic and visceral body domains. Whether these central changes are reversible in patients with chronic CRPS I is unclear. The central changes possibly affect the endogenous control system of nociceptive impulse transmission. Coupling between the sympathetic neurons and the afferent neurons in the periphery (open arrow) is one component of the pain in patients with SMP. However, it seems to be unimportant in those without SMP. Note that SMP and pain that is not dependent on the sympathetic nervous system can exist in parallel in the same patient (adopted from Janig w 2000).

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  Figure 7 Three phase bone scan image of CRPS patient with pain duration of 13 months. Precipitating event was operation of right calcaneus fracture. Right ankle and whole metatarsophalangeal joints show hot uptake in blood pool and delayed image.

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  Figure 8 Treatment algorithm for CRPS (adopted from Stanton-Hicks M 2002).

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  Figure 9 A CRPS patient suffering with 4 months of pain duration shows severe swelling of right hand (A). He had various interventional treatment including the sympathetic ganglion block as well as strong analgesics for 3 months, however his pain and swelling did not disappear. Spinal cord stimulation (SCS) was tried 5 months after the pain onset, his symptom was gradually improved. One month after the SCS his right hand swelling marked diminished (B) and he could get right hand grip (C).

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