Complex Regional Pain Syndrome Type 1 (Reflex Sympathetic Dystrophy) Treatment & Management

Updated: Mar 21, 2023
  • Author: T P Sudha Rao, MD; Chief Editor: Herbert S Diamond, MD  more...
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Approach Considerations

United Kingdom guidelines on complex regional pain syndrome (CRPS) list four ‘pillars’ of CRPS care: education, pain relief (medication and procedures), physical rehabilitation, and psychological intervention. All four are of equal importance, and addressing them may require involvement of a range of specialties, such as physiotherapy, pain medicine, rheumatology, neurology, and surgery. [14]

International guidelines for the management of CRP, sponsored by the Reflex Sympathetic Dystrophy Syndrome Association (RSDSA) and most recently updated in 2022, acknowledge the paucity of high-level studies, and thus base the recommendations on literature review supplemented with clinical expertise. The guidelines include a treatment algorithm focused on functional restoration provided by an interdisciplinary team (eg, occupational, physical, recreational therapist; vocational rehabilitation counselor). [15]

In addition, the guidelines recommend providing access to medications, psychotherapy, and/or injections from the start of treatment, if needed and appropriate. If the patient cannot begin treatment or fails to progress with treatment at any step or in any regard, consideration should be given to starting or adding more or stronger medication, more intensive psychotherapies, and/or different interventions.

The functional restoration algorithm has four parts. Initial measures include the following:

  • Mirror visual feedback
  • Graded motor imagery
  • Reactivation
  • Contrast baths
  • Desensitization
  • Exposure therapy

The second phase of therapy includes the following:

  • Edema control
  • Flexibility (active)
  • Isometric strengthening
  • Correction of postural abnormalities
  • Diagnosis and treatment of secondary myofascial pain

The third phase of therapy includes the following:

  • Stress loading
  • Isotonic strengthening
  • Range of motion (gentle, passive)
  • General aerobic conditioning
  • Postural normalization and balanced use

The fourth phase of therapy includes the following:

  • Ergonomics
  • Movement therapies
  • Normalization of use
  • Vocational/functional rehabilitation

Indications for pharmacotherapy and suggested choices include the following [15] :

  • Mild-to-moderate pain – Simple analgesics and/or blocks
  • Excruciating, intractable pain – Opioids and/or blocks or later, more experimental interventions
  • Inflammation/swelling and edema – Steroids, systemic or targeted (for acute treatment) or nonsteroidal anti-inflammatory drugs (for long-term treatment); immune modulators
  • Depression, anxiety, insomnia – Sedative, analgesic antidepressant/anxiolytics (and/or psychotherapy)
  • Significant allodynia/hyperalgesia – Anticonvulsants and/or other sodium channel blockers and/or N-methyl-D-aspartate (NMDA) receptor antagonists (eg, ketamine)
  • Significant osteopenia, immobility and trophic changes – Calcitonin or bisphosphonates
  • Profound vasomotor disturbance – Calcium channel blockers, sympatholytics, and/or blocks

Virtual reality is increasingly under study for treatment of CRPS. This approach expands on principles of mirror therapy, and appears to provide reduction in pain and increase in function. [16, 17]

For information on physical medicine approaches to CRPS, see Physical Medicine and Rehabilitation for Complex Regional Pain Syndromes


Medical Care

The natural history of type 1 CRPS is variable and unpredictable, the pathogenesis is unknown, and few controlled treatment trials exist. Thus, published recommendations rely heavily on expert opinion, and the approach depends largely on the specialty of the treating physician. Even if a disturbance in sympathetic nervous system function is important in the development of the clinical syndrome, not all patients respond to sympatholytic medications or to chemical or surgical sympathectomy.

Clinical experience teaches that early recognition and treatment are necessary to avoid permanent disability and that the effectiveness of treatment is limited once the patient has reached the chronic fibrotic stage. Certainly, the incidence and severity of CRPS can be greatly reduced by initiating prophylactic measures in situations that are known to be triggers (eg, hemiplegic stroke, Colles fracture). These measures include immediate and aggressive mobilization of the involved extremity with passive and then active range-of-motion exercises. Similarly, in patients with established CRPS, physical and occupational therapy are key components of any therapeutic regimen.

Two major approaches to the medical treatment of early CRPS 1 exist: sympathetic blockade and anti-inflammatory therapy. Although these are not mutually exclusive, the order of usage is generally specialty-dependent, with anesthesiologists/surgeons starting with the former and internists/rheumatologists starting with the latter.

Radiofrequency ablation, such as stellate ganglion ablation, cervical-thoracic, and lumbar sympatholysis, has been tried in refractory cases. [18, 19] A case report describes sustained relief of intractable lower limb pain using ultrasound-guided pulsed radiofrequency, in a patient who developed CRPS after a burn injury to the saphenous nerve. [20]

Sympathetic block

Sympathetic nerve blocks are first-line interventional treatment options for patients with CRPS. Stellate ganglion blocks are used for CRPS of the upper extremities, while lumbar sympathetic blocks are used for CRPS of the lower extremity. [21]

For CRPS affecting an upper extremity, inject a local anesthetic into the stellate and upper dorsal sympathetic ganglia to block the efferent sympathetic impulses from the involved extremity. Lidocaine or bupivacaine, with or without epinephrine, is usually used. Guanethidine has been used, but was found to be no more effective than placebo, and was associated with significant adverse effects. [22]

This procedure warms the skin, inhibits sweating, and causes flushing. A successful blockade is indicated by the development of ipsilateral Horner syndrome, ie, ptosis, miosis, and enophthalmos.

Symptoms usually abate within 30 minutes, confirming the diagnosis. Once adequate blockade has been achieved, ensure that the patient participates in hand therapy. Although the interruption lasts only a few hours, the benefits may persist for several days.

Use 1-2 blocks per week. An average of 4-5 blocks is required to permanently relieve symptoms. For symptoms that are not adequately relieved after 4-5 blocks, institute a continuous stellate blockade via a subcutaneously placed catheter or conduct an operative sympathectomy.

For lower-extremity CRPS, a lumbar block is used.

A systematic review found insufficient evidence to draw firm conclusions regarding the efficacy or safety of sympathetic blockade with local anesthetic, but determined that the limited data available do not suggest the technique is effective for reducing pain in CRPS. [23]

Sympatholytic drugs

Sympatholytic drugs alone may be effective in early disease. In later stages of the disorder, sympatholytic drugs may be beneficial in combination with sympathetic block or sympathectomy.

Regional intravenous sympathetic blockade with sympatholytic drugs, such as phenoxybenzamine, using a Bier block–like procedure may be helpful, but results have varied. This is most useful in early disease.

A randomized study suggested that intrathecal baclofen, a GABA-receptor agonist, relieved the dystonia and, in some cases, the hand pain in patients with CRPS. [24] This suggests that GABA-ergic inhibitory pathways may also be important in the pathogenesis of CRPS.

Other medications

Nonsteroidal anti-inflammatory drugs (NSAIDs) may provide some pain relief in patients with CRPS. However, they are not effective in altering the skin changes or natural history of the process and thus play only a supportive role.

A review of the use of anticonvulsants and antidepressants for treatment of CRPS-related pain found insufficient evidence to support the use of gabapentinoids, but noted that three randomized controlled trials (RCTs) did report significant improvement in pain with gabapentin, whereas one RCT found amitriptyline to be as effective as gabapentin. The efficacy of pregabalin has been described in pediatric patients with early CRPS, but only in case reports rather than RCTs. [25]

A course of high-dose corticosteroids (eg, prednisone 30-40 mg/d tapering over 2-4 weeks) can dramatically reduce pain, swelling, and stiffness. This enables the institution of an aggressive physical-therapy program. In general, corticosteroids are of most value in early CRPS (acute and subacute) when the bone scan shows increased uptake in the involved extremity.

Calcitonin is not an anti-inflammatory medication per se but has been reported to reverse the inflammatory changes and reduce pain in early CRPS, especially in patients with hyperdynamic blood flow. Subcutaneous injections of 100-160 units are administered daily for 4-8 weeks, then every other day for 3-6 weeks. A few reports suggest that intranasal calcitonin [26] may also be effective in treating RSD.

Oral and intravenous bisphosphonates (eg, alendronate) have demonstrated benefit in early CRPS. [27] In a randomized, double-blind, placebo-controlled trial, the aminobisphosphonate neridronate, administered intravenously, provided significant and persistent benefit in patients with CRPS. [28] Neridronate has received orphan drug designation by the US Food and Drug Administration for treatment of CRPS.

The anesthetic agent ketamine has shown promise in the treatment of CRPS. Intravenous administration of subanesthetic doses and topical application have been studied. However, the optimum dose and the route and timing of administration remain to be determined. [29, 30, 31]


Surgical Care

Surgical procedures used for CRPS include the following:

  • Upper thoracic or lumbar sympathectomy
  • Chemical sympathectomy
  • Spinal cord stimulator implantation
  • Amputation

For more information, see Surgery for Reflex Sympathetic Dystrophy (Complex Regional Pain Syndrome Type 1).

Upper thoracic or lumbar sympathectomy 

Consider surgical sympathectomy if the relief achieved with sympathetic blockade and anti-inflammatory therapy has not permanently resolved the CRPS and relapse has occurred despite continuing treatment. These procedures are reserved for patients who have had an initial response to sympathetic blockade and are thus likely have a sympathetically mediated process. Choose sympathectomy early in the course of disease because once joint fibrosis develops, minimal functional improvement occurs. Pain relief, however, remains significant in late disease.

Considerations include the following:

  • Indications include disease duration of longer than 6 months and failure of permanent resolution despite five percutaneous sympathetic blocks.

  • The most significant improvement following surgical sympathectomy is pain relief, although circulation, range of motion, strength, and function usually improve somewhat

  • If surgery of the involved extremity is required, perform it after the sympathectomy

  • Ensure that a surgical sympathectomy is performed by an adequately trained individual

Chemical sympathectomy

For chemical sympathectomy, phenol or alcohol in injected to ablate the sympathetic chain. Perform this only if the patient is at a very high surgical risk for hoarseness from a recurrent laryngeal nerve injury, lung injury, or permanent Horner syndrome.

Spinal cord stimulation

Epidural implantation of a spinal cord stimulator has been shown to provide significant, prolonged pain relief and functional improvement in CRPS (hand or foot). [32, 33] In the United Kingdom, the National Institute for Health and Care Excellence (NICE) recommends spinal cord stimulation as a possible treatment for adults with chronic pain of neuropathic origin, including CRPS, who have had chronic pain for at least 6 months despite standard treatments and have had a successful trial of spinal cord stimulation as part of an assessment by a specialist team. [34]

In the ACCURATE trial, conducted in 152 subjects with CRPS or causalgia in the lower extremities, stimulation of the dorsal root ganglion (DRG) proved more effective than dorsal column (spinal cord stimulation, SCS) stimulation. At 3 months, the percentage of patients reporting ≥50% pain relief and treatment success was greater in the DRG arm than in the SCS arm (81.2% versus 55.7%, respectrively; P< 0.001). [35]

A case series in four patients who had a DRG stimulator implanted after experiencing incomplete relief with SCS stimulation reported that concomitant DRG and SCS stimulation may provide better improvement in pain and function than use of either device alone. When the SCS stimulator was turned off, the patients consistently reported reduced pain relief and function. [36]


Amputation is sometimes performed in patients with severe complications of CRPS type 1 who have severe, untreatable inflammation with the threat of sepsis or severe functional impairment. Patients who are in despair may request amputation as a last resort. [37, 29]

Two evidence-based guidelines found insufficient evidence that amputation makes a positive contribution to the treatment of CRPS 1. [37, 29] A more recent study that compared pain, function, depression, and quality of life in 19 patients with intractable CRPS who underwent amputation, and 19 patients in whom amputation was considered but not performed, reported consistently better results in the amputation group and recommended considering amputation for patients with intractable CRPS. [38]



Multiple consultants are often needed in challenging CRPS cases, including the following:

  • An anesthesiologist who specializes in pain management and who is capable of performing sympathetic blocks
  • An internist/rheumatologist capable of supervising anti-inflammatory regimens
  • A surgeon who is capable of performing surgical sympathectomy

Consultation with a physical therapist and occupational therapist (hand therapist) is important to institute aggressive exercise programs.



Knowing the triggers for complex regional pain syndrome (CRPS), especially extremity immobilization for any cause, and recognizing the disease process early and instituting prompt therapy are the most important aspects of prevention.

A retrospective cohort study in 542 patients who underwent subacromial shoulder surgery found that prophylactic use of vitamin C, 500 mg/day orally for 50 days postoperatively, reduced the risk of developing CRPS 1 by more than 50%. The incidence of CRPS 1 in patients who received vitamin C, versus those who did not, was 7% versus 13% (P = 0.009). [39]


Physical and Occupational Therapy

As discussed above, an aggressive range-of-motion exercise program is an essential part of CRPS management. However, especially after sympathetic block or sympathectomy, this may have to be a graduated regimen, with patient-directed passive range of motion to tolerance and, later, active range of motion. When appropriate (eg, in patients with hemiplegia), the entire extremity requires attention.

Following the stellate block or sympathectomy, hand therapy may proceed without causing further pain. Ensure that the therapist does not cause pain, usually by avoiding application of passive motion. Patients can safely apply passive motion because they know when motion becomes painful.

Other features of physical therapy include the following:

  • Massage of the involved extremity is an important component of therapy
  • The patient requires close follow-up, education, and encouragement to maintain an exercise routine
  • Heat therapy relaxes muscle spasms, improves motion, and relieves pain
  • Judicious use of splinting with Thermoplast and Velcro straps in the balanced hand position may help to prevent shortening of the collateral ligaments of involved joints and may provide intermittent pain relief; the splint must be comfortably fit, and needs to be removed frequently throughout the day for exercise and massage
  • Record routine measurements of the patient's strength and range of motion; this provides encouragement to the patient and facilitates communication between the therapist and the treating physician

A meta-analysis of 33 randomized controlled trials published between 1995 and 2021 found low-quality evidence that mirror therapy and graded motor imagery programs may result in large improvement in pain and disability in poststroke CRPS patients. The meta-analysis also found low-quality evidence that adding pain exposure therapy and aerobic exercises to physical therapy may result in improvement in pain. [40]