Complex Regional Pain Syndrome · What It Is, Causes, Signs and Symptoms, Treatment, and More

Complex regional pain syndrome (CRPS), formerly known as reflex sympathetic dystrophy, is a chronic disorder characterized by continuous pain, skin changes, and limited range of motion in an affected body region (e.g., arm, leg, hand, foot). Complex regional pain syndrome often occurs following trauma and affected individuals experience pain that is disproportionate to the initial injury.  

There are two subtypes of CRPS including type I, which is CRPS without evidence of peripheral nerve injury; and type II, which is CRPS with evidence of peripheral nerve injury. CRPS type I is the most common subtype and it is present in over 90 percent of affected individuals. Another classification system distinguishes CRPS by “warm” and “cold” subtypes. Warm CRPS is distinguished by increased skin temperature at the onset of symptoms, suggesting increased blood flow to the area and/or the presence of inflammation, whereas the cold CRPS subtype presents with decreased skin temperature at symptom onset.

The exact cause of CRPS is unknown, but there are several proposed theories involving peripheral and central nervous system dysfunction, abnormal feedback responses to pain, chronic inflammation, and genetic factors.  

CRPS often arises after injury or trauma to a peripheral limb, which can damage nerves in the peripheral nervous system (i.e., CRPS type II). Following the initial insult, these damaged peripheral nerves may transmit abnormal pain signals to the brain and spinal cord (i.e., central nervous system), causing the brain to think that the body is experiencing pain out of proportion. Over time, the central nervous system undergoes a process known as “central desensitization,” where it becomes overly sensitive to small pain stimuli and produces an exaggerated pain response.  

Other theories have suggested that chronic inflammation could play a role. It appears that the chronic pain and allodynia (i.e., pain due to a stimulus that does not typically elicit pain) seen in CRPS are a result of inflammatory mediators (e.g., interleukin 2 and 6) and pain-producing peptides (e.g., substance P, neuropeptide Y, calcitonin gene-related peptides) released by peripheral nerves.  

CRPS pathogenesis may also be related to genetic factors, as several identified genes have been associated with the disorder, namely HLA-DQ1 and HLA-DR3. Human leukocyte antigen (HLA) genes encode proteins on cell surfaces and modulate the immune system. The incidence of CRPS appears to be higher in genetic females, particularly those who are postmenopausal.  

Signs and symptoms of CRPS include pain, sensory and motor dysfunction, and skin changes in the affected limb. The pain is often characterized as a burning or tearing sensation that may be exacerbated by movement, temperature, or stress. Individuals may experience sensory changes such as hyperalgesia (i.e., increased sensitivity to pain) and allodynia; and motor impairments, such as a decreased ability to move the affected body part due to pain or a reduction in muscle strength. Skin changes may include contraction or fibrosis of connective tissue and joints of the affected area and changes in skin color and texture. Autonomic changes may also be present, including differences in skin temperature and edema. 

Diagnosis of CRPS begins with an initial review of symptoms and medical history. The Budapest consensus criteria were proposed to facilitate the clinical diagnosis of CRPS. It requires individuals to experience continuous pain that is disproportionate to the inciting event, along with the presence of at least one subjective symptom in three of the four following categories:  
(1) Sensory (e.g., allodynia, hyperesthesia)  

(2) Vasomotor (e.g., skin color or temperature changes)  

(3) Autonomic (e.g., edema, sweating) 

(4) Motor (e.g., decreased range of motion) 

Additionally, individuals must display at least one objective sign in two of the four aforementioned categories at the time of evaluation. For example, a physical examination may help elicit sensory changes via pinprick testing or observing skin color changes.  

While imaging tests (e.g., X-ray, bone scintigraphy) are not required in diagnosing CRPS, they can either support or exclude the diagnosis when individuals present with atypical features. For example, an X-ray may show patchy osteoporosis in the affected limb, and bone scintigraphy (i.e., a specific test that involves injecting a radioactive tracer that is attracted to areas of bone with increased turnover) may demonstrate increased radiotracer uptake in the affected area, which can both be supportive of a CRPS diagnosis. 

Management of CRPS consists of a combination of nonpharmacologic and pharmacologic strategies aimed at controlling pain and improving the individual’s quality of life. Treatment is most effective when started early, therefore, prompt treatment initiation can help prevent the spread of symptoms adjacent to the initially affected areas.  

Nonpharmacologic strategies include avoiding identified triggers and participating in an individualized physical therapy or occupational therapy program to improve strength, mobility, motor function, and functional status.   

Pharmacologic and interventional strategies to manage pain are utilized in a graded fashion, beginning with topical creams including lidocaine and capsaicin, and oral non-steroid anti-inflammatory drugs (NSAIDs) like ibuprofen or naproxen. If the pain is neuropathic (e.g., allodynia, hyperalgesia, and perceptions of pain in the absence of a stimulus due to nervous system dysfunction), antidepressants (e.g., duloxetine, amitriptyline) or nerve modulators (e.g., gabapentin, pregabalin) may be used.  

In individuals with persistent pain that is not responsive to medications, procedures or interventions including sympathetic nerve block(i.e., injection of local anesthetic into nerves to prevent neuronal firing and transmission of pain signals); intravenous regional sympathetic blocks (i.e., injection of anti-adrenergic medications like guanethidine into the vein of the affected area with the application of a tourniquet to the extremity, to occlude circulation); intrathecal drug pumps (i.e., a procedure which uses an implanted catheter to deliver pain medications directly into the spinal fluid); and spinal cord stimulation (i.e., a procedure which uses an implanted device to deliver electrical impulses to the spinal cord to relieve pain) may be considered.