An Overview of Complex Regional Pain Syndrome and its Management
Complex regional pain syndrome (CRPS) is a chronic pain syndrome of unclear etiology. Prior to 1994, CRPS was divided into two conditions: reflex sympathetic dystrophy, which included a history of initiating injury (type 1); and causalgia, which included a history of known nerve injury (type 2).1 CRPS typically affects an extremity, such as the hand or foot, and frequently follows a traumatic event such as a fracture, sprain, surgery, immobilization (tight casts or frozen shoulder), and even stroke.2,3 However, patients may not know what precipitated CRPS—physicians may hear “it just happened,” for instance, after striking one’s hand but without significant injury.
CRPS is a complex medical problem and, for the patient, a significant source of suffering, disability, and poor quality of life for those afflicted—in fact, the pain and disability of CRPS are much worse than the initial injury. Furthermore, there are no clear and uniform current guidelines on the treatment and management of the disease. This article provides an overview of the pathophysiology and management of CRPS with recommendations on when specialized pain management and interventions may be most beneficial.
The pathophysiology of CRPS is unknown but is likely to be multifactorial, with neuropathic, autonomic, vascular, and inflammatory components, as well as both peripheral dysfunction and central sensitization.2-7 Dysfunction of peripheral nociceptive fibers (lightly myelinated A-delta fibers and unmyelinated C fibers) after repetitive noxious stimuli can result in lowered pain thresholds and enhanced activation of dorsal horn cells, leading to the hyperalgesia of CRPS.7,8 Central sensitization via afferent processing by second-order nociceptor-specific neurons and wide-dynamic-range (WDR) neurons in the spinal cord lead to changes in dorsal horn morphology and are thought to be the cause for the allodynia and spread of pain past the initial site of injury seen in some CRPS patients.7,8
The autonomic nervous system dysfunction is thought to be a main source of the vasomotor, temperature, hydrosis, and trophic changes seen in CRPS.7-9 Current theories suggest that the sympathetic and nociceptive systems in CRPS are coupled in an aberrant manner such that the sympathetic efferents activate the sensory afferents, leading to persistent afferent activity.7-11 Neurogenic inflammation may also be involved and contribute to the vasodilation, protein extravasation, and edema seen in CRPS via release of neuropeptides such as calcitonin gene-related peptide, substance P, and proinflammatory cytokines like tumor necrosis factor.7,10,11 However, it is unclear what maintains the inflammatory process throughout the disease.
Higher central nervous system changes in the cortex may be involved; contralateral (to affected side) somato-sensory cortex reorganization, bilateral motor cortex disinhibition, and thalamic disinhibition have all been demonstrated in patients with CRPS.7,11-13 The neural plasticity in cortical restructuring may be responsible not only for the motor symptoms seen in many CRPS patients, but contribute to the maintenance and progression of the disease.
CRPS is a clinical diagnosis made with history, presentation, and exam; tests may be useful to support the diagnosis or rule out other differentials. The diagnostic criteria for CRPS as set by the International Association for the Study of Pain includes “the presence of an initial noxious event or cause for immobilization of the affected region, continuing pain disproportionate to the inciting event, and the presence of edema, changes in skin blood flow, or abnormal sudomotor activity in the affected region sometime during the course of the syndrome.”1
The condition often starts in an extremity, though can occur anywhere in the body, and is characterized by a combination of autonomic, sensory, and vasomotor symptoms. The hallmark of CRPS is pain out of proportion to the severity of the initial injury.1,2,4 Pain, temperature asymmetry, edema, impaired movement, change in skin color, hyperesthesia, hyperalgesia, hyperpathy, tremors, involuntary movements, muscle spasms, paresis, pseudoparalysis, skin, muscle and bone atrophy, hyperhidrosis, and changes in hair and nail growth have all been reported in patients with this syndrome (Figure 1).1-4,6 In regards to temperature changes, the initial symptom is usually a warmer sensation in the affected area and heat hyperalgesia; this may progress to cold hyperalgesia and lower skin temperature on the affected side.4,6
The natural history of CRPS has been described in three stages. The first stage is characterized by pain, burning, temperature hyperalgesia, local edema, and restricted mobility. The second stage is generally a worsening of the edema, skin thickening, atrophy, and wasting of the muscles in the affected region. The third stage is when symptoms have worsened to limited range of motion, irreversible skin and nail changes, hair growth changes, and demineralization seen on x-ray.2-6 Because these characteristics can intermingle at any given time, and since there is not a reliable progression along these stages, the staging of CRPS has fallen out of favor.
Tests can be supportive in the diagnosis or ruling out of other differentials. One test to consider is nerve conduction studies or electromyograms (EMGs), which test only the large (fast-conducting) myelinated fibers in mixed peripheral nerves, and can reveal peripheral neuropathy.4 They do not test the pain transmitting small A-δ and C fibers implicated in painful, small fiber neuropathies. Nerve conduction studies and EMGs are normal in CRPS type 1, but may be abnormal in CRPS type 2—reflecting the nerve damage that is associated with type 2. Punch skin biopsies are rarely performed but can reveal a cutaneous sensory neuropathy common in small fiber and inheritable neuropathies but there are no findings that are specifically diagnostic for CRPS.4-6 Quantitative sensory testing (QST) may be helpful in assessing small fiber function; however, in the assessment of CRPS it is still primarily a research tool rather than a diagnostic clinical test. Plain radiographs (x-rays) may show demineralization and osteopathic changes in chronic and more severe cases. A bone scan with technetium, or bone density scan, may reveal earlier osteoporotic changes than plain film. Thermography, QST, and sweat tests may be positive for specific symptoms of CRPS (abnormal sensation, hyperhidrosis, or temperature gradients) but are not diagnostic.4-6,14,15
There is current controversy over whether sympathetic blocks may be helpful diagnostically.16 A positive response is unpredictable but indicates sympathetically maintained pain, while an ineffective block suggests that the pain is sympathetically independent but does not rule out the diagnosis of CRPS.