Neuropathic pain including Reflex Sympathetic Dystrophy and CRPS
- Understanding neuropathic pain
- Making the diagnosis
- Assessing results
- Glossary of terms for neuropathic pain
I. Understanding neuropathic pain
It is important for health-care professionals and patients to recognize neuropathic pain for two reasons. First, treatment is different from other pain conditions; there are treatments unique to this condition. For example, drugs like anti-convulsants that one would never consider prescribing for arthritis pain or toothache can be extremely effective in alleviating neuropathic pain. Second, it is likely that early intervention prevents increased morbidity in some cases, and therefore health-care professionals must be able to recognize and treat neuropathic pain early before it becomes well-established, self perpetuating, and refractory to treatment.
Definition of neuropathic pain: The international Association for the study of pain defines neuropathic pain as pain “initiated or caused by a primary lesion or dysfunction in the nervous system”. Inclusion of the term dysfunction makes this destination somewhat vague and an alternative definition is: “Pain caused by a lesion of the peripheral or central nervous system (or both) manifesting with sensory symptoms and signs”.
This can be a difficult concept to grasp at first, and comparison of neuropathic pain to the more familiar type of pain may help. Most pain syndromes are what experts call “nociceptive pain”. “Visceral pain” is usually given its own special category, but for purposes of simplicity and clarity this information point will compare neuropathic pain to nociceptive pain.
Nociceptive pain follows stimulation of specialized pain sensing organs in tissues, called nociceptors. Examples are high threshold mechanoreceptors and C polymodal receptors. The purpose of these specialized organs (called “nociceptors”) is to warn the central nervous system of stimuli that signal potential for tissue damage. The warning is perceived as pain. Pain from a cut, a burn, infection, a fracture, and from surgery exemplifies nociceptive pain. The pain in these conditions is the consequence of activation of nociceptors that transduce unacceptable tissue levels of pressure, temperature, and chemical stimuli into electrical discharge along specialized pain-dedicated axons in peripheral nerves (Aδ and c fibers). These axons transmit a pain signal to the spinal cord where complex neural circuitry in the dorsal horn modulates painful stimuli. The modulated message of tissue pain is next transmitted up the spinal thalamic tract and other spinal cord pathways to the brain where pain is perceived. This is the sequence of sensory events that occurs when we step on a tack while walking barefoot at home.By comparison, neuropathic pain does not involve transduction of painful stimulation by nociceptors; it originates from within the nervous system itself. It is the consequence of an injury, a metabolic disorder, or other damage to the peripheral or central nervous system. Familiar examples of neuropathic pain are:
- Painful diabetic neuropathy
- Post herpetic neuralgia
- Post amputation phantom limb pain
- Pain from spinal cord injury
- Neuralgia of a single nerve following injury, for instance following inguinal herniorrhaphy
- Cervical and lumbar radiculopathy (nerve root compression)
- Post stroke pain
- Complex regional pain syndrome (reflex sympathetic dystrophy) (link to brief info point on reflex sympathetic dystrophy)
Nociceptive pain Neuropathic pain:
Pain originates from peripheral nerve or
central nervous system
There are multiple pathologic processes that lead to neuropathic pain. This explains how this condition can present differently in different patients. To learn more about the basic science understanding of various pathologic processes that lead to neuropathic pain, please see the basic science of neuropathic pain info point (link to Todd’s 3 page summary for medical students)
II. Making the diagnosis – the key competencyNeuropathic pain can be distinguished from nociceptive pain on the basis of history, exam, laboratory studies, imaging, and in some cases even tissue biopsy. There are research definitions of post herpetic neuralgia, complex regional pain syndrome (reflex sympathetic dystrophy), diabetic neuropathy, and other common neuropathic pain conditions but no generally accepted and validated clinical diagnostic criteria exist for either the these specific neuropathic pain conditions or neuropathic pain in general. There is active research in this area, but for now the best we can do is learn how to generate a high level of suspicion for neuropathic pain. The tools most important for primary care practice are
- Exam – The European Federation of Neurological Societies guidelines state that “an accurate sensory exam is often sufficient to reach a diagnosis”.
- Negative search for a “nociceptive” explanation for pain (for example no fracture, infection, tumor, etc. that would adequately explain your patient’s pain severity, location, and persistence)
Testing will be mentioned briefly, but is by and large beyond the scope of this information point.History
No single symptom is pathognomonic. The features of the history that will increase your suspicion for neuropathic pain can be grouped into six general categories. Whenever neuropathic pain is suspected each category should be probed at least briefly, but the most important to remember and watch for are in the first category: character and quality of the pain:
- Character and quality of the pain
- Neuropathic pain is often described as burning or electrical/shooting.
- Neuropathic pain may be surprisingly severe in the absence of any observable evidence for injury. Severity of the pain can be followed using the University of Washington neuropathic pain scale, this has been shown to be sensitive to treatment effects (link to info point #12a)
- Normally in painful sensations may become painful – Allodynia. Patients may complain of sensitivity to the touch of bed sheets, clothing, bath water, air-conditioning, etc.
- Pain in the distribution of the peripheral nerve or nerve root suggests damage to a peripheral nerve.
- Diffuse pain in a limb suggests pathology involving the central nervous system that has altered pain sensation in an entire region of the body.
Associated sensory phenomena
- There may be numbness consequent to nerve injury. The presence of numbness in an area perceived as painful by the patient is often confusing to those unfamiliar with neuropathic pain, yet it is a hallmark of neuropathic pain. To learn more about our basic science understanding of this numb/painful phenomenon please see the basic science of neuropathic pain info point (link to Todd’s 3 page summary for medical students)
- There may be tingling or other odd sensations called dysesthesia (such as “ants crawling on my skin” and other sensations that are so far out of the usual realm of experience that patients may be reluctant to describe them for fear of being disbelieved).
Associated autonomic instability limited to the painful region of the body
- Change in skin color (consequent to changes in skin blood flow).
- Unusual dryness or moistness of the skin compared to the contralateral limb/body part.
History of neurologic injury – traumatic, infectious, metabolic, etc.
- Onset of pain immediately after surgery or other trauma where seemingly “insignificant” peripheral sensory nerves may have been damaged.
- Evidence of diabetic neuropathy.
- Acute herpes zoster infection.
- Many, many other possible scenarios.
Excellent response to anticonvulsant drugs that are known to have no effect on nociceptive pain.
- Gabapentin and others
General vascular, musculoskeletal, and neurological exam is beyond the scope of this info point, but of course should be performed. By inspection and brief neurological exam, one can further assess the key areas described above in the history. Some basic principles to follow:
- Believe with the patient tells you regarding their perception of pain and encouraged them to use whenever descriptive terms come to mind.
- When doing sensory testing, the patient should be instructed to respond in simple terms. Patient should be asked to say first whether the stimulus applied to the painful area causes the same sensation as in unaffected areas or whether it is more intense or less intense. They may then be allowed to describe their perception of the quality of the stimulus. For example, pinprick may be less sharp in the painful area compared to the identical contralateral unaffected area, but the patient may describe odd painful sensations that continue well after the examiner stops tapping the affected area with the pin.
- Inspection – in the painful area look for edema, pallor or redness. In more long-standing cases look for dystrophic shiny skin with either increased or decreased hair growth, abnormal nail growth.
- Palpation – deal for temperature difference between the painful area and its contralateral counterpart. Feel for increased or decreased sweat production.
- Sensory exam – you are looking for evidence of altered sensory processing because this suggests neuropathic pain. These can be described in common language or using the terms below. Using a light stroke of the cotton swab and clean pin to test the painful area, adjacent skin, and matching contralateral anatomy:
- Evaluate for areas of decreased sensation (hypoesthesia, and when there is absolutely no ability to feel stimulus, anesthesia) and for areas of enhanced feeling (hyperesthesia, and when there is exaggerated response to pinprick hyperalgesia)
- Evaluate for presence of pain to normally nonpainful stimuli: Allodynia. For example, light stroking with the cotton swab causes pain-withdrawal response.
- Evaluate for unusual sensations in response to sensory stimuli, such as tingling in response to pinprick or stroking with a cotton swab: Dysesthesia.
- EMG/NCV – Occasionally, electrodiagnostic testing with nerve conduction velocity and EMG is useful in distinguishing peripheral nerve pathology from more proximal root or plexus injury. EMG/NCV does not test small C fibers and many neuropathic pain syndromes almost exclusively involve pathology of these axons. It is also quite a painful test for patients with neuropathic pain. Therefore a normal test will be generated, adding to the patient’s confusion and anxiety that they will not be believed (and sometimes accomplishing this in fact). Therefore there must be a very clear diagnostic question posed before this test is undertaken.
- Somatosensory evoked potentials are generally available but useful only in the same way as EMG/NCV and has the same limitations regarding testing only larger nerve fibers.
- Imaging – MRI and CT scan are occasionally useful in evaluating for compression of nerve root, brachial plexus, lumbar plexus, spinal cord, and of Peripheral nerve by tumor or other mass lesion. Specific indications should be present before ordering these tests for the same reason as the EMG/NCV. One does not want to generate a dossier of negative unnecessary diagnostic tests.
- For specific testing (bone scan and thermogaphy) sometimes used in complex regional pain syndrome (reflex sympathetic dystrophy and causalgia) see info point # (info point on RSD).
III. TreatmentTreatment of neuropathic pain falls into the following categories:
- Physical therapy and occupational therapy
- Patient education, support, and reassurance
Specialty referral for
- Corrective surgery
- Anesthetic injections
- Palliative surgery
- Behavioral medicine
- Occupational medicine
- Complementary medicine
- Assessing results
Before discussion of specific treatment options, one overriding principal of treatment of neuropathic pain needs to be mentioned: Painful anatomic pathology such as nerve entrapment, right instability, or fractures must be corrected before neuropathic pain can be successfully treated. This is particularly true in the case of complex regional pain syndrome (reflex sympathetic dystrophy). Abnormal sensory processing in the central nervous system may be maintained indefinitely as long as there is a painful peripheral lesion. A thorough evaluation that may involve a variety of specialists or may be coordinated through a full-service pain medicine clinic is needed to search for and treat painful peripheral lesions whenever possible.Pharmacotherapy is the mainstay of therapy at the primary care level. The following can be excerpted from evidence based AHCPR guidelines (link to AHCPR guidelines) for treatment of neuropathic pain and is recapitulated in a recent review of evidence based therapy . The evidence is based mainly on controlled trials of drugs for painful diabetic neuropathy and postherpetic neuralgia. The applicability of results of clinical trials for one chronic neuropathic pain syndrome to others has not been rigorously tested, however most “first-line” therapies have been tested with multiple types of neuropathic pain and have shown similar results.
- Gabapentin or Lyrica
- Tricyclic antidepressants
- Nortriptyline is somewhat less sedating than amitriptyline, but the dosing is similar: 10 milligram h.s. slowly titrating every 3-7 days to 75-150mg.
- Tramadol HCL maximum 400 mg/day in help the patients
- Opioid analgesics. It is commonly believed that neuropathic pain is resistant to opioid analgesics, but they have a role. 5 randomized controlled trials of opioid analgesics for neuropathic pain have been published since 1998, all suggesting that opioids can play a role in good management, and`leading to their selection as first line medications.
- 5% lidocaine patch applied to skin and areas of sensitivity to touch (allodynia).
Second line in pharmacotherapy (at least one randomized control trial supporting use in various neuropathic pain conditions)
- Lamotrigine 25 mg b.i.d. titrated initially to 400 mg per day
- Carbamazepine, particularly in trigeminal neuralgia
- Other anticonvulsants.
- Venlafaxine and bupropion
- Topical agents such as Capsaicin
Physical therapy and occupational therapy has a role in teaching the patient how to function optimally around the painful body part, for maintaining strength, cardiovascular conditioning, range of motion and joint function. The evidence supporting efficacy is inconsistent (there is no strong support for “desensitization therapy”, for example); most of this evidence is for treating complex regional pain syndrome (reflex sympathetic dystrophy and causalgia). Pain in the affected body part often interferes with direct manipulation. To learn more about physical therapy and occupational therapy in neuropathic pain disorders such as complex regional pain syndrome (reflex sympathetic dystrophy and causalgia) , link to: http://www.guideline.gov/summary/summary.aspx?doc_id=3204)
- Lumbar sympathetic block for lower extremity neuropathic pain
- Cervical and thoracic sympathetic block (“stellate ganglion” block and others) for upper extremity and facial neuropathic pain, including acute herpes zoster and post herpetic neuralgia.
- Epidural bolus and infusion of local anesthetic using a temporary percutaneous and sometimes tunneled epidural catheter.
- Local anesthetic/steroid infiltration of injured peripheral nerves at the site of injury (neuroma injection).
Corrective surgery includes decompression of nerve root (the familiar partial diskectomy for disc herniation compressing nerve root and decompressive laminectomy/facetectomy for spinal stenosis) decompression of peripheral nerve entrapment, resection of painful neuromas with re-embedment of proximal severed nerve to less vulnerable anatomic location (common in treating neuropathic pain following a medical limb amputation, for example), stabilization of unstable or painful joint that may be perpetuating neuropathic pain.Palliative surgery includes
- Reversible neuro-augmentative procedures such as spinal cord and deep brain stimulation, implantation of intrathecal infusion devices, (Link to Chabal procedure info point on spinal cord stimulation and intrathecal infusion therap)
- Neuroablative procedures.
Neuroablative procedures vary according to the type of neuropathic pain, and examples of these procedures include sympathectomy, peripheral neurolysis, dorsal rhizotomy, cordectomy, anterolateral cordotomy, mesencephalotomy, and cingulotomy. One of the more common is permanent sympathectomy. The majority of the information available on this procedure is for complex regional pain syndrome (reflex sympathetic dystrophy and causalgia). The AHCPR guideline on treatment of reflex sympathetic dystrophy states: “Data published by the Reflex Sympathetic Dystrophy Syndrome Association (RSDSA) suggests that sympathectomy in properly selected RSD/CRPS patients may provide one of the most effective treatments for RSD/CRPS.” However, a 2005 Cochrane review on the use of permanent sympathectomy (surgical or chemical) for neuropathic pain states: “The practice of surgical and chemical sympathectomy is based on poor quality evidence, uncontrolled studies and personal experience. Furthermore, complications of the procedure may be significant, in terms of both worsening the pain or producing a new pain syndrome; and abnormal forms of sweating (compensatory hyperhidrosis and pathological gustatory sweating). Therefore, more clinical trials of sympathectomy are required to establish the overall effectiveness and potential risks of this procedure.” (http://www.update-software.com/Abstracts/AB002918.htm)
Peripheral neurolysis has a role occasionally, particularly when a peripheral nerve has already been severely injured, for instance chemical neurolysis of intercostal nerve for pain following incidental neurectomy during thoracotomy. Neurolysis of intact sensory nerve, particularly when the nerve has cutaneous innervation, always poses the risk of inducing neuropathic pain in its own right.
For specific pain syndromes, especially spinal cord injury and brachial plexus injuries, dorsal root entry zone lesioning (DREZ) has been performed for many years (to learn more link to http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat1.chapter.64890).
Results of clinical trials of neuroablative procedures for chronic neuropathic pain tend to have similar deficiencies and lead to no solid conclusion regarding safety and efficacy. These results do not apply to the cancer pain population, for whom neuroablative procedures are sometimes required for pain control.Behavioral medicine services should be employed when possible to
- Define and treat (or to accommodate when refractory to treatment) patient characteristics that interfere with successful medical therapy: social circumstances, beliefs, behaviors, and Axis I and II pathology. As the example of beliefs and behaviors that can interfere with good outcome, patients may have unrealistic expectations regarding results of medical therapy and frequently have not had adequate education and counseling to understand and accept the limitations imposed by their medical problem (in this case, pain). (To learn more, link to the info point on behavioral predictors of poor outcome )
- Quantify and direct treatment of depression, which is a likely in patients with chronic neuropathic pain as it is in all patients with chronic pain. Careful assessment for depression and suicide risk at regular intervals combined with appropriate pharmacologic and counseling is frequently necessary link to info points #5 and #6)
- Cognitive and behavioral therapy techniques such as relaxation, guided imagery, and biofeedback may have a role, although no consistent literature exists supporting their use in chronic neuropathic pain. (link to info point #7)
Occupational medicine consultation for evaluation of work-related issues is particularly important in working patients when their pain-related disability is not so severe that they are obviously unable to perform work of any kind. Determination of work status and assistance with return to work, perhaps with restrictions and modification of the work environment, is possible through occupational medicine specialists. Outside of the industrial injury patient population, this is a vastly underutilized although usually available service. (To learn more about occupational medicine and treating chronic pain, link to info point #15)
Complementary medicine there is no quality data available on efficacy of acupuncture and other modalities. (To learn more about complementary medicine for pain treatment, link to info point__)
IV. Assessing results
The University of Washington neuropathic pain scale (link to info point 12a) can be used to follow pain severity, and it is sensitive to treatment effects. According to the neuropathic pain assessment guidelines published by The European Federation of Neurological Societies, quality of life parameters are adequate even for research purposes. Info point #14 provides background information on functional assessment and The Brief Pain inventory is a simple to use and adequate tool for accomplishing pain severity assessment and functional assessment (including quality of life) in primary care clinics. (link to info point #13)
V. Glossary of terms rated to neuropathic painAnesthesia: Complete lack of ability to perceive sensory stimulus.
Allodynia: Normally none painful sensations (such as light touch or air-conditioning or cool or warm water) are perceived as painful.
Dysesthesia: Altered sensation, not perceived as painful. For instance, light touch is perceived as tingling, cold is perceived as warm.
Hyperesthesia: Stronger than expected intensity of perceived stimulus. For example, light touch is perceived as much stronger on one side of the body compared to the other side and adjacent skin.
Hyperalgesia: A special case of hyperesthesia in which painful stimuli are perceived as stronger than expected compared to the opposite side of the body and adjacent skin.
Hypoesthesia: Less than expected intensity of perceived stimulus, less than adjacent skin and the opposite side of the body.
Reflex Sympathetic Dystrophy/Complex Regional Pain Syndrome
Complex Regional Pain Syndrome (CRPS) is a clinically defined entity that is a neuropathic pain syndrome. This entity includes two related syndromes that have been well described in the literature and whose names continue to be used:
- Reflex Sympathetic Dystrophy (CRPS type I)
Causalgia (CRPS type II)
- History of the Terms
- Diagnosis of CRPS
- Treatment of CRPS
History of the Terms
The term “causalgia” was first used in 1867 to refer to a burning pain associated with peripheral nerve wounds. These wounds often occurred in battle and led to prolonged burning pain after the injury had apparently healed. Physicians also noticed that there were frequently overlying skin changes, such as “glossy skin” and increases in skin temperature associated with the pain. Others soon noted similar findings that were associated with soft tissue (but not nerve) injury, and in 1946 Evans first used the term “reflex sympathetic dystrophy” to describe these findings.
In 1953 John Bonica sought to group all syndromes associated with severe post-injury pain and focal vasomotor disturbances, whatever the initiating event, under one heading, reflex sympathetic dystrophy (RSD). Bonica and his colleagues believed that the underlying etiology of RSD was a disturbance in the sympathetic nervous system. This was manifested by the vasomotor changes associated with RSD and supported by the observation that many patients with RSD reported relief with sympathetic nerve blocks.
Unfortunately, there remained a lack of consensus and a gold standard for defining RSD. Therefore, many terms persisted in the literature. These included not only causalgia and RSD, but “posttraumatic spreading neuralgia,” “Sudeck’s atrophy,” and “shoulder-hand syndrome.” In 1993 a consensus group of pain experts sought to reconsider the clinical syndrome of severe disabling pain after soft tissue or nerve injury that was associated with regional skin, sensory, and motor abnormalities. This group recognized that many such patients did not attain relief with sympathetic nerve block and sought to abandon the term RSD altogether. The group developed the term CRPS and published diagnostic criteria for it in 1994 Stanton-Hicks M, 1995 [Reference: Pain. 1995 Oct;63(1):127-33.]). The diagnostic criteria for CRPS are purely clinical and the major difference between CRPS Type I and CRPS Type II is whether the initiating event was a soft tissue injury (Type I) or a nerve injury (Type II).
Practically, the nomenclature remains confused. Physicians who specialize in pain medicine, insurance companies, and legal entities continue to use the terms RSD and causalgia. The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) defines causalgia as a mononeuritis of the upper (355.4) or lower (355.71) limb, which may not describe many patients with this syndrome nor may it be applicable in the absence of a clear peripheral nerve injury. RSD is defined under codes 337.20-337-29. It does not use the terms CRPS. RSD at all.
Diagnosis of CRPS
- The presence of an initiating noxious event, or a cause for immobilization
- Continuing pain, allodynia, or hyperalgesia that is disproportionate to any inciting event in severity
- Evidence at some time of edema, changes in skin blood flow, or abnormal sudomotor activity in the region of pain
- Exclusion of conditions that would otherwise account for the degree of pain and dysfunction. The distinction between CRPS with (type 2) and without (type 1) nerve injury is based on findings on physical exam electromyography (EMG) and nerve conduction studies (NCS).
The Reflex Sympathetic Dystrophy Syndrome Association has published a guideline for the diagnosis, treatment, and management of RSD/CRPS. (Link to http://www.rsds.org/3/clinical_guidelines/index.html#diagnosis) This guideline states:The diagnosis of RSD/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:
- Abnormal function of the sympathetic nervous system.
- Movement disorder
- Changes in tissue growth (dystrophy and atrophy)
The pain and symptoms of RSD/CRPS may exceed both the magnitude and duration of symptoms expected from the normal healing process expected from the inciting event. Similarly, the RSD/CRPS diagnosis is precluded by the existence of known pathology that can be explained by the observed symptoms and degree of pain. There are “grades” of this syndrome described in the literature with symptoms ranging from minor to severe.
The staging of CRPS has never been shown to be of any clinical use.
Note on psychological aspects of CRPS. Profound emotional and behqavioral changes often follow the onset of this condition, but it has often been postulated that there are certain “psychological predisposing factors”. A review of the literature from the late 1800s to 1992 found “No worhtwhile evidence to substantiate the cliam that psychological factors or certain personality traits predispose one to develop RSD” (Lynch M Psychological aspects of reflex sympathetic dystrophy: a review of the adult and paediatric literature Pain 1992;49:337-347)
In general, laboratory testing is not particularly helpful in the diagnosis and management of neuropathic pain. (Link to #46) and this includes CRPS. Bone scan has been such a popular test tha it deserves some attention. Its use was supported by early literature (Kozin F The Reflex Sympathetic Dystrophy Syndrome Am J Med 1976; 60:332-338). A more recent review of the literature found that bone scan is positive in only 55% of cases of CRPS, and this was close to a random pattern (Lee GW The role of bone scan scintigraphy in diagnosisn reflex sympathetic dystrophy J Hand Surgery 1995;20:458-463). Moreover, another study found triphase bone scan non-specific for CRPS (could not pick the CRPS patients from others), even in post-sympathectomy patients (Mailis A Alteration of the three phase bone scan after sympathectomy Clin J Pain 1994;10:146-155). Bone scan therefore appears to have little value in diagnosisng CRPS. Thermography can demonstrate an abnormal change in skin temperature, but it suffers from lack of validation and normative data. The European Federation of Neurological Societies notes that, “In the clinical setting, a neurological examination that includes an accurate sensory examination is often sufficient to reach a diagnosis” (of neuropathic pain, including CRPS) [Cruccu G, 2004] (Ref: Eur J Neurol. 2004 Mar;11(3):153-62.)
Treatment of CRPSThe treatment of CRPS is the therapy of neuropathic pain. Specific guideline recommendations include: (Link to http://www.rsds.org/3/clinical_guidelines/index.html#diagnosis)
- Education about normal use and goals of therapy
- Facilitating movement of the affected body part through activities of daily living
- Sequential trials of medications for neuropathic pain
- Appropriate use of sympathetic nerve blocks
- Other invasive therapies as appropriate
Cruccu G, Anand P, Attal N, Garcia-Larrea L, Haanpaa M, Jorum E, Serra J, Jensen TS. EFNS guidelines on neuropathic pain assessment. Eur J Neurol. 2004 Mar;11(3):153-62.
Galer BS, Schwartz L, Allen RJ. Complex regional pain syndromes – Type I: reflex sympathetic dystrophy, and Type II: causalgia. In: Loeser JD, Butler SH, Chapman CR, Turk DC (Eds.) Bonica’s Management of Pain. 3rd Edition. Philadelphia, PA, Lippincott Williams & Wilkins; 2001:388-411.
Kirkpatrick AF (Editor). Reflex Sympathetic Dystrophy / Complex Regional Pain Syndrome (RSD/CRPS) Clinical Practice Guidelines (Second Edition Updated October 15, 2000)for the diagnosis, treatment, and management of Reflex Sympathetic Dystrophy Syndrome (RSD) also known as Complex Regional Pain Syndrome (CRPS). 2000. RSDSA. Available at: http://www.rsds.org/3/clinical_guidelines/index.html#diagnosis,
Merskey H, Bogduk N. Classification of chronic pain: Descriptions of chronic pain syndromes and definition of pain terms 2nd Ed. Seattle, Washington: IASP Press; 1994
Stanton-Hicks M, Janig W, Hassenbusch S, Haddox JD, Boas R, Wilson P. Reflex sympathetic dystrophy: changing concepts and taxonomy. Pain. 1995 Oct;63(1):127-33.