Complex regional pain syndrome (CRPS)

The complex regional pain syndrome, or CRPS for short, is a neuropathic pain syndrome that can occur after injuries or surgical procedures on the upper or lower extremities. It manifests as pain, swelling, redness, warmth, and loss of function in the limbs, without any infection present. The exact cause of the condition is still unknown to this day. However, early detection is extremely important. The earlier the condition is treated, the greater the chances of recovery. Neurostimulation techniques such as spinal cord stimulation (SCS) and dorsal root ganglion stimulation (DRG) have proven to be very effective for CRPS therapy. Both procedures are performed at Inselspital for patients with CRPS.

What is complex regional pain syndrome?

CRPS is one of the most well-known neuropathic pain syndromes. Specifically, it is a complication resulting from an injury to one of the extremities. The body responds to the injury with an excessive inflammatory response without an infection causing it. The injury may be a fracture, surgery, trauma, or nerve injury. Whether CRPS occurs and how severe CRPS is does not depend on the severity of the injury.

In rare cases, CRPS can also occur without prior injury or surgery, i.e. without any apparent cause at all. However, in such cases a diagnosis must be made by elimination, i.e. the physician must first rule out all other possible causes for the symptoms that occur *.

What are the symptoms of CRPS?

In the first phase, CRPS is manifested by pain that is disproportionately severe compared to the normal healing process. In addition, changes such as swelling, discoloration, hyperthermia or hypothermia as well as restrictions in mobility in the area of the pain can be observed. It is important to know that all these symptoms do not develop in the area of the initial trauma, but usually further away from the site of injury *.

Over time, the inflammation-like symptoms recede. However, the pain, which extremely restricts the patient in everyday life, remains.

How is CRPS classified?

CRPS can be classified according to causative factors (etiology), severity or skin temperature.

Classification according to etiology

CRPS type 1 without nerve injury

The term Sudeck's disease is still frequently used for CRPS type 1 – named after its discoverer, the German surgeon Paul Sudeck (1866-1945). CRPS type 1 occurs without a previous nerve injury. This is the case, for example, after

  • conservatively treated bone fractures
  • contusions
  • surgery on the upper or lower extremities

CRPS type 2 with nerve injury

CRPS type 2, also known as causalgia, manifests itself as a burning pain that occurs as a result of a demonstrable nerve injury. This is the case, for example, after

  • trauma with injury to a nerve
  • surgery on the nerves of the upper or lower extremities

Classification according to severity

Three stages of the disease have been defined. However, the classification into degrees of severity is not always clear-cut, as individual symptoms can overlap and the progression of the disease varies greatly from person to person. Treatment is generally based on the respective stage of the disease *:

  • Stage 1, acute stage (0–3 months): acute inflammatory swelling, burning pain at rest, pain at the site of injury, sensory and motor disturbances.
  • Stage 2, dystrophic stage (3–6 months): diffuse pain, stiffening of the affected joint, edema, muscle atrophy, decalcification of the bone.
  • Stage 3, atrophic stage (6–12 months): end stage, no pain, irreversible tissue atrophy, generalization of symptoms.

Classification according to skin temperature

CRPS can also be categorized based on the initial skin changes. If the skin is warm and red at the beginning of the symptoms, it is referred to as "warm CRPS". If the initial pain is accompanied by cold, livid (bluish) skin, the CRPS is referred to as "cold". This classification is important for the prognosis, as patients with initially cold CRPS have a poorer prognosis *.

How common is CRPS?

CRPS occurs in 6–26 of every 100,000 people per year *, *. People aged 40–60 years are most frequently affected, women usually more often (in a ratio of 3:1). Similarly, it was observed that the upper limbs are more affected than the lower limbs with a frequency of 3:2 *.

What is the cause of CRPS?

The precise mechanism of origin of CRPS remains unclear to date. The following theory is discussed: Patients with CRPS experience impaired wound healing after an injury to the extremities. An inflammatory reaction develops in the area of the lesion. Inflammatory mediators are produced that can no longer be broken down. These substances enter the central nervous system, where they lead to sensory changes in the area of the spinal cord and to remodeling processes in the brain*.

In addition, psychological factors such as depression facilitate the development of complex regional pain syndrome *.

How is CRPS treated?

CRPS is a rather difficult disease to treat. Treatment of CRPS must always be tailored to the individual patient, and not everyone responds equally well to therapy. Early diagnosis and multidisciplinary therapy are important for better success rates in treatment *.

There have been numerous studies to determine which is the most effective therapy for complex regional pain syndrome. However, there is still no generally accepted optimal therapy. One reason for this is that the published studies have mainly investigated the effect on different symptoms of CRPS (pain, mobility).

Conservative therapy of CRPS

In the first stage of the disease, the acute stage, the focus is on pain treatment with steroids, bisphosphonates, anticonvulsants (gabapentin, pregabalin), opioids (morphine) or ketamine.

Physiotherapy to passively promote mobility and the evaluation and treatment of concomitant psychological disorders (if necessary, therapy with antidepressants) are recommended from this stage.

In the second stage (dystrophic stage) and third stage (atrophic stage), the focus is on physical therapy and occupational therapy as well as psychotherapy, since acute inflammation is no longer present in these stages. Analgesic therapy is also important in these stages. If this does not provide sufficient pain relief, neuromodulation procedures may be considered.

Neuromodulatory treatments for CRPS

The majority of studies in the literature have been conducted to evaluate spinal cord stimulation and dorsal root ganglion stimulation. There are few studies that have investigated other neuromodulation techniques such as motor cortex stimulation, deep brain stimulation, or transcranial stimulation.

Spinal cord stimulation (SCS)

The first large study to investigate the effect of spinal cord stimulation (SCS) was conducted in 2008 and showed that SCS in combination with physiotherapy provided better relief of pain symptoms than physiotherapy alone. However, after 3 years there was no difference in pain symptoms between the group with SCS stimulation and physiotherapy on one side and the group with physiotherapy alone on the other side. One potential explanation is that pain in CRPS patients increases as they progress and SCS stimulation alone is no longer sufficient to provide the desired pain relief *.

It should be noted that we now have newer forms of stimulation (high-frequency stimulation at 10 kHz or burst stimulation), which have largely replaced the traditional forms of stimulation of the past.

In 2012, a larger prospective study was conducted to examine the long-term outcome of patients with SCS. This study showed that spinal cord stimulation provided at least a 30% reduction in pain for at least 63% of CRPS patients. Follow-up was conducted over 12 years; however, there was no comparison group treated conservatively * as in the 2008 Kemler study *. In light of these findings, SCS was implemented as a "standard of care," or practice-based treatment guideline, for patients with CRPS.

Spinal cord stimulation

Dorsal root ganglion stimulation

In addition, a new option for stimulation has recently been developed, dorsal root ganglion stimulation (DRG). The first large study to investigate the effect of DRG stimulation compared to SCS was the ACCURATE study *. The study showed that over a 12-month period, more patients with DRG stimulation benefited from neuromodulation than patients with SCS (81% versus 56%). Pain reduction was greater than 50% in these patients.

Dorsal root ganglion stimulation is not only effective for patients who have never had SCS. It can also lead to an improvement in pain symptoms in patients with previous spinal cord stimulation who experience a loss of efficacy over time *.

Dorsal root ganglion stimulation

Why you should seek treatment at Inselspital

At Inselspital, CRPS patients are first evaluated by a multidisciplinary pain team.

Before neuromodulatory therapy is started and the stimulator is definitively implanted, a test phase is always performed to determine whether the patient will benefit from neuromodulation.

Both stimulation procedures are performed regularly at our hospital, so we have a lot of experience in this field.. Based on current studies, DRG stimulation is preferable to SCS. However, there are exceptions to this. Anatomical reasons or previous spinal surgeries may argue in favor of performing SCS.


  1. Birklein F, Dimova V. Complex regional pain syndrome-up-to-date. Pain Rep. 2017;2:e624.

  2. Guthmiller KB, Varacallo M. Complex Regional Pain Syndrome (Reflex Sympathetic Dystrophy, CRPS, RSD). StatPearls. Treasure Island (FL): StatPearls Publishing; 2020.

  3. Vaneker M, Wilder-Smith OH, Schrombges P, de Man-Hermsen I, Oerlemans HM. Patients initially diagnosed as ‘warm’ or ‘cold’ CRPS 1 show differences in central sensory processing some eight years after diagnosis: a quantitative sensory testing study. Pain. 2005;115:204-211.

  4. Birklein F. et al. Diagnostik und Therapie komplexer regionaler Schmerzsyndrome (CRPS). Deutsche Gesellschaft für Neurologie (Hrsg.). 2018.

  5. Sandroni P, Benrud-Larson LM, McClelland RL, Low PA. Complex regional pain syndrome type I: incidence and prevalence in Olmsted county, a population-based study. Pain. 2003;103:199-207.

  6. de Mos M, de Bruijn AG, Huygen FJ, Dieleman JP, Stricker BH, Sturkenboom MC. The incidence of complex regional pain syndrome: a population-based study. Pain. 2007;129:12-20.

  7. Goh EL, Chidambaram S, Ma D. Complex regional pain syndrome: a recent update. Burns Trauma. 2017;5:2.

  8. Kemler MA, de Vet HC, Barendse GA, van den Wildenberg FA, van Kleef M. Effect of spinal cord stimulation for chronic complex regional pain syndrome Type I: five-year final follow-up of patients in a randomized controlled trial. J Neurosurg. 2008;108:292-298.

  9. Geurts JW, Smits H, Kemler MA, Brunner F, Kessels AG, van Kleef M. Spinal cord stimulation for complex regional pain syndrome type I: a prospective cohort study with long-term follow-up. Neuromodulation. 2013;16:523-9; discussion 529.

  10. Deer TR, Levy RM, Kramer J et al. Dorsal root ganglion stimulation yielded higher treatment success rate for complex regional pain syndrome and causalgia at 3 and 12 months: a randomized comparative trial. Pain. 2017;158:669-681.

  11. Yang A, Hunter CW. Dorsal Root Ganglion Stimulation as a Salvage Treatment for Complex Regional Pain Syndrome Refractory to Dorsal Column Spinal Cord Stimulation: A Case Series. Neuromodulation. 2017;20:703-707.