Complex Regional Pain Syndromes



Complex Regional Pain Syndromes


Sudhir A. Diwan

Vinod Malhotra

Neel D. Mehta

Mohammad M. Piracha





A. Medical Disease and Differential Diagnosis



  • What is the differential diagnosis of pain in this patient?


  • What is complex regional pain syndrome (CRPS)?


  • What are the two types of CRPS?


  • What are the diagnostic criteria for CRPS? What is the incidence of this disease?


  • Define allodynia, hyperalgesia, hyperesthesia, and dysesthesia.


  • What are the associated stages of CRPS?


  • What are the possible etiologies of CRPS?


  • Explain the pathophysiology of the development of CRPS.


  • Define sympathetically maintained pain (SMP) and sympathetically independent pain (SIP).


  • How does CRPS differ from neuralgia?


  • What is central pain? How will you differentiate central pain from CRPS?


  • Is the social history of this patient relevant to the development of chronic pain syndrome?


B. Pain Management



  • How will you work up CRPS type I and II?


  • Describe the sympathetic nerve supply to the arm?


  • Where is the stellate ganglion located?


  • What are the anatomic landmarks used in the stellate ganglion block?


  • What are the clinical signs of stellate ganglion block?


  • What is Horner syndrome?


  • After a stellate ganglion block, this patient reports no significant change in the degree of pain despite developing Horner syndrome. Is the pain psychogenic in this patient?


  • What types of nerve fibers are interrupted in stellate ganglion block?


  • What is a differential block?


  • What are the two major classes of local anesthetics? Describe the major differences in their clinical pharmacology.



  • What factors determine the onset, potency, and duration of a local anesthetic block?


  • How does the addition of epinephrine to commercially available premixed solutions affect the efficacy of local anesthetics?


  • How will you treat this patient?


  • What is the pharmacologic management of CRPS?


  • What is the role of intravenous regional block (Bier method) in diagnosis and treatment of CRPS?


  • Compare and contrast the mechanism of actions of ketamine and methadone.


  • What roles does ketamine infusion play in the treatment of CRPS?


  • What is the role of spinal cord stimulation (SCS) and surgical sympathectomy?




A. Medical Disease and Differential Diagnosis


A.1. What is the differential diagnosis of pain in this patient?

Pain accompanied by burning and temperature change in this patient is most likely due to CRPS. The differential diagnosis may also include the following:



  • Peripheral neuropathy


  • Soft tissue injury


  • Vascular insufficiency (Raynaud disease)


  • Nerve entrapment syndrome (carpal tunnel syndrome)


  • Brachial plexopathy

Over the years, CRPS has been referred to as reflex sympathetic dystrophy (RSD), causalgia, SMP, and chronic peripheral pain syndrome. The term CRPS was introduced in 1994 by the International Association for the Study of Pain subcommittee on taxonomy. It is subdivided into CRPS type I (formerly described as RSD) and CRPS type II (formerly described as causalgia).



Jänig W, Stanton Hicks M, eds. Progress in Pain Research and Management. Seattle, WA: IASP Press; 1996:79-92. Reflex Sympathetic Dystrophy: A Reappraisal; vol 6.

Merskey H, Bogduk N, eds. Relatively generalized syndromes. In: Classification of Chronic Pain. 2nd ed. Seattle, WA: IASP Press; 1994:39-56.

Stanton-Hicks M, Jänig W, Hassenburch S, et al. Reflex sympathetic dystrophy: changing concepts and taxonomy. Pain. 1995;63:127-133.


A.2. What is complex regional pain syndrome (CRPS)?

CRPS is characterized by pain associated with sensory, autonomic, trophic, and motor abnormalities. CRPS is triggered by noxious stimuli (type I) or by nerve injury (type II). It is not limited to the distribution of a single peripheral nerve and is disproportionate to the inciting event.

RSD, causalgia, algodystrophy, Sudeck atrophy, and various other conditions are all grouped under CRPS. This diagnosis better describes the wide range of clinical signs and symptoms and the complexity of the pathophysiology responsible for the clinical picture.



Marinus J, Moseley GL, Birklein F, et al. Clinical features and pathophysiology of complex regional pain syndrome. Lancet Neurol. 2011;10:637-648.

Merskey H, Bogduk N, eds. Relatively generalized syndromes. In: Classification of Chronic Pain. 2nd ed. Seattle, WA: IASP Press; 1994:39-56.

Stanton-Hicks M, Jänig W, Hassenburch S, et al. Reflex sympathetic dystrophy: changing concepts and taxonomy. Pain. 1995;63:127-133.



A.3. What are the two types of CRPS?

CRPS-I is defined as a clinical syndrome triggered by a noxious stimulus that is not limited to the distribution of a single peripheral nerve; no nerve lesion can be identified. CRPS-II is defined as a clinical syndrome that is due to a nerve injury and is mostly limited to the distribution of the injured nerve. The diagnostic criteria are the same for CRPS-I and II.



Marinus J, Moseley GL, Birklein F, et al. Clinical features and pathophysiology of complex regional pain syndrome. Lancet Neurol. 2011;10:637-648.

Stanton-Hicks MD, Burton AW, Bruehl SP, et al. An updated interdisciplinary clinical pathway for CRPS: report of an expert panel. Pain Pract. 2000;2(1):1-16.


A.4. What are the diagnostic criteria for CRPS? What is the incidence of this disease?

The diagnosis of CRPS can be made in the following context: a history of trauma to the affected area associated with pain that is disproportionate to the inciting event plus one or more of the following as defined by either the Orlando criteria or a modified version referred to as the Budapest criteria.



  • Abnormal function of the sympathetic nervous system (vasomotor changes, skin color changes)


  • Swelling


  • Movement disorder


  • Changes in tissue growth (dystrophy and atrophy)


  • Sensory disturbances (hyperalgesia or allodynia)

The main features include pain that is continuous, burning in nature, independent of type and severity of injury, and not limited to a dermatomal distribution. Patients may complain of allodynia, dysesthesia, or hyperalgesia. Movement or stress exacerbates pain. Edema is usually present. Abnormal sudomotor activity, limb discoloration, and local temperature changes are common but inconsistent.

It affects between 200,000 and 1.2 million Americans. This syndrome may follow as many as 5% of all traumatic injuries with the arms being affected in approximately 60% of cases and the legs about 40%.



Fishman SM, Ballantyne JC, Rathmell JP, eds. Bonica’s Management of Pain. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:314-331.

Marinus J, Moseley GL, Birklein F, et al. Clinical features and pathophysiology of complex regional pain syndrome. Lancet Neurol. 2011;10:637-648.


A.5. Define allodynia, hyperalgesia, hyperesthesia, and dysesthesia.



  • Allodynia: pain caused by a stimulus that normally does not provoke pain (i.e., touching with a cotton swab)


  • Hyperalgesia: an increased response to a stimulus that is normally painful (i.e., increased response to pinprick)


  • Hyperesthesia: increased sensitivity to a stimulus either due to a diminished threshold or an increased response to stimuli that are normally recognized. Hyperesthesia includes both allodynia and hyperalgesia.


  • Dysesthesia: an abnormal sensation that is unpleasant to the patient. It may be either spontaneous or evoked (i.e., lumbar radiculopathy).



Fishman SM, Ballantyne JC, Rathmell JP, eds. Bonica’s Management of Pain. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:314-331.


A.6. What are the associated stages of CRPS?


Stage I



  • Onset of severe pain limited to the site of injury


  • Increased sensitivity of skin to touch and light pressure (hyperesthesia)



  • Localized swelling


  • Muscle cramps


  • Stiffness and limited mobility

At the onset, the skin is usually warm, red, and dry; then it may change to blue (cyanotic) in appearance and become cold and sweaty.



  • Increased sweating (hyperhidrosis)


  • In mild cases, this stage lasts a few weeks and then subsides spontaneously or responds rapidly to treatment.


Stage II



  • Pain becomes even more severe and more diffuse.


  • Swelling tends to spread and it may change from a soft to hard (brawny) type.


  • Hair may become coarse then scant; nails may grow faster and become brittle, cracked, and heavily grooved.


  • Spotty wasting of bone (osteoporosis) occurs early but may become severe and diffuse.


  • Muscle wasting begins.


Stage III



  • Marked wasting of tissue (atrophic) eventually becomes irreversible.


  • For many patients, the pain becomes intractable and may involve the entire limb.


  • A small percentage of patients have developed generalized RSD, affecting the entire body.



Fishman SM, Ballantyne JC, Rathmell JP, eds. Bonica’s Management of Pain. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:314-331.


A.7. What are the possible etiologies of CRPS?

CRPS may follow relatively minor trauma with or without nerve injury. Causes leading to CRPS include the following:



  • Injuries to peripheral tissues (e.g., fractures, dislocations, and postoperative state)


  • Inflammatory conditions (e.g., fasciitis, tendonitis, bursitis, and arthritis)


  • Immobilization as a result of injury or cast application


  • Peripheral nerve injury resulting from direct compression or ischemia (e.g., brachial plexopathy, postherpetic neuralgia, and nerve root injury)


  • Central nervous system insults (e.g., head injury, ischemia, and brain tumor)


  • Spinal cord lesions


  • Idiopathic



Fishman SM, Ballantyne JC, Rathmell JP, eds. Bonica’s Management of Pain. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:314-331.


A.8. Explain the pathophysiology of the development of CRPS.

Several hypotheses have been postulated, but none can explain all the findings and the varying responses to treatment in these patients. These hypotheses include the following:



  • Abnormal discharges in sympathetic and nociceptive afferents produced by trauma


  • Sensitization of peripheral sensory receptors produced by sympathetic hyperactivity


  • Formation of ephapses (artificial synapses) after peripheral nerve injury


  • Spontaneous neuronal ectopy at the site of demyelination or axonal injury


  • Central reorganization of pain processing (central sensitization)

More than one sequence of events likely take place in a patient, giving rise to a mixed clinical picture. A dynamic change in the physiology and structure of central pain projecting neurons mediated through the N-methyl-D-aspartate (NMDA) receptor. Injury initiates and maintains a state of central sensitization in the central pain pathways, resulting in a lower threshold to fire pain transmission neurons and an increase in their receptive fields. This may involve disinhibition of spinal and trigeminal nociceptive neurons. This often
precedes thermal and mechanical allodynia and spontaneous pain. Finally, the psychological component and neuromodulation cannot be discernibly separated.



Benzon H, Rathmell JP, Wu CL, et al, eds. Raj’s Practical Management of Pain. 4th ed. St. Louis, MO: Mosby; 2008:427-431.

Marinus J, Moseley GL, Birklein F, et al. Clinical features and pathophysiology of complex regional pain syndrome. Lancet Neurol. 2011;10:637-648.

McMahon SB, Koltzenburg M, Tracey I, et al, eds. Wall and Melzack’s Textbook of Pain. 6th ed. New York: Churchill Livingstone; 2013:961-977.


A.9. Define sympathetically maintained pain (SMP) and sympathetically independent pain (SIP).

The pain that is maintained by sympathetic innervation or circulating catecholamines is defined as SMP. It describes a pain mechanism, not a clinical syndrome. Therefore, by definition, patients with CRPS who report pain relief after a sympathetic block (e.g., stellate ganglion block) have SMP. Conversely, pain conditions that show features of sympathetic overactivity, yet fail to respond to sympathetic blocks, are described as SIP.



Fishman SM, Ballantyne JC, Rathmell JP, eds. Bonica’s Management of Pain. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:314-331.


A.10. How does CRPS differ from neuralgia?

The chronic pain seen in neuralgia is usually paroxysmal in nature and follows the distribution of nerve. The pain is sharp and shooting without associated vasomotor or sudomotor changes. The chronic pain syndrome of CRPS is a sustained, diffuse, burning pain that is independent of nerve distribution and is associated with vasomotor and sudomotor changes, edema, allodynia or hyperalgesia, and changes in skin color.

Only gold members can continue reading. Log In or Register to continue

Mar 18, 2021 | Posted by in ANESTHESIA | Comments Off on Complex Regional Pain Syndromes
Premium Wordpress Themes by UFO Themes