eMedicine Specialties > Physical Medicine and Rehabilitation > Upper Limb Musculoskeletal Conditions

Complex Regional Pain Syndromes: Treatment & Medication

Author: Manish K Singh, MD, Assistant Professor, Department of Neurology, Teaching Faculty for Pain Management and Neurology Residency Program, Hahnemann University Hospital, Drexel College of Medicine; Medical Director, Neurology and Pain Management, Jersey Institute of Neuroscience
Coauthor(s): Jashvant Patel, MD, Medical Director, Department of Pain Medicine and Comprehensive Rehabilitation, Medical College of Pennsylvania Hahnemann University; John Grothusen, PhD, Director of Quantitative Sensory and Autonomic Nervous System Laboratory, Assistant Professor, Department of Neurology, MCP Hahnemann University; Patrick M Foye, MD, FAAPMR, FAAEM, Associate Professor of Physical Medicine and Rehabilitation, Co-Director of Musculoskeletal Fellowship, Co-Director of Back Pain Clinic, Director of Coccyx Pain Service (Tailbone Pain Service: www.TailboneDoctor.com), University of Medicine and Dentistry of New Jersey, New Jersey Medical School
Contributor Information and Disclosures

Updated: Sep 22, 2009

Treatment

Rehabilitation Program

Physical Therapy

It is extremely important for patients with RSD to undergo a steady progression from gentle weight bearing to progressive, active weight bearing.14 Gradual desensitization to increasing sensory stimuli also plays an important role. The altered processing in the CNS is typically reset by a gradual increase in normalized sensation. Other intervention should be offered to enable greater confidence and comfort when patients do not progress in a reasonable amount of time.

Physical therapy (PT), in association with occupational therapy (OT), plays an important role in functional restoration. The goal is to increase strength and flexibility gradually, beginning with gentle gliding exercises. Patients usually are reluctant to participate in PT because of intense pain. A self-directed or therapist-directed PT program is important and should be individualized to each patient's needs and goals.

Patients with CRPS also may have myofascial pain syndrome. A study by Rashiq and Galer found that myofascial pain syndrome can be treated first, and if it is treated effectively, the entire syndrome may resolve.15 Myofascial pain may be treated with modalities and techniques, such as massage and myofascial release.

Occupational Therapy

An analysis by Steverens and colleagues noted that occupational therapists are very important for initiating gentle, active measurements and preliminary desensitization techniques with patients who have RSD.16

Occupational therapists usually are responsible for introducing and maintaining a stress-loading program for patients with CRPS. This program involves active compression and distraction exercises that provide stimuli to the affected extremity without joint motion. The scrubbing technique requires use of a scrub brush. Scrubbing is performed by gradually increasing the weight on the patient's affected extremity as he/she scrubs in circles. Weight loading of the joints is completed with increasing weight as the scrubbing process continues.

The next part in this program involves a carrying technique. The patient is instructed to carry a weight (bag) in the affected extremity throughout the day, as tolerated. The patient should monitor his/her symptoms and keep a daily record to share with the therapist.

The stress-loading program usually is started as a home exercise program. The patient also can use desensitization techniques (eg, rubbing the skin, massage, tapping, vibration) to reduce sensitivity and pain.

Recreational Therapy

Recreational therapy can help the patient with chronic pain to take part in pleasurable activities that help to decrease pain. The patient finds enjoyment and socialization in previously lost or new recreational activities. Usually, patients with chronic pain are depressed. Recreational therapists may play an important role in the treatment process and enable the patient to become active.

Vocational therapy should be recommended and initiated early for all appropriate patients. Vocational therapy can provide work capacities and targeted work hardening, and the patient may return to gainful employment.

Medical Issues/Complications

Therapeutic strategies include pharmacologic pain relief, sympatholytic interventions, and rehabilitation.

  • All treatments should focus primarily on functional restoration. Use of drugs, sympathetic blocks, and psychotherapy helps to achieve good pain control during PT.
  • Early intervention is important. The key to successful treatment of RSD is recognition of symptoms in stage I or early in stage II. Physicians should be alert to signs and symptoms of RSD. When RSD is suspected, the treating physician should ensure that that the patient receives evaluation by a pain specialist or other clinician experienced in treating this condition.
  • The time between the start of RSD and clinic attendance may vary from several days to years.
  • Identifying any underlying disease (eg, fracture, sprain, radiculopathy) and tailoring specific management are important.
  • Johnston and Howell reported significant pain improvement after release and anterior transposition of the nerve.17 Five patients had RSD, 3 cases of which resolved after nerve release. Careful evaluation with diagnostic local nerve blocks and other conservative measures should be tried before surgery is considered.
  • Sympathetic or somatic block, if performed, should be integrated into a good rehabilitation program.

Surgical Intervention

  • Sympathetic blocks:
    • For the upper extremity, a stellate (cervicothoracic) ganglion block is recommended. Bupivacaine is preferred over lidocaine because of its longer half-life. Not all patients experience pain relief after blocks.
    • Percutaneous lumbar sympathetic plexus catheter placement usually provides short-term pain relief in most patients and may have some long-term effect.
  • Bier block (intravenous regional block):
    • In 1974, the concept of intravenous regional guanethidine was introduced. Block with bretylium or reserpine has less profound effect than it does with guanethidine, which may last for 2-3 days.
    • A double-blind, randomized study was designed to compare the effectiveness of intravenous regional sympatholysis using guanethidine, reserpine, and normal saline; the study reported significant pain relief in all 3 groups. No significant differences were noted among the 3 groups in the degree of pain relief. The saline group's high rate of pain relief could be due partially to a mechanism of tourniquet-induced analgesia.
  • Somatic block, consisting of continuous epidural infusion with different variants of brachial plexus blocks, includes an axillary, supraclavicular, or infraclavicular approach that may be useful.
  • Dorsal column stimulator:
    • Localized extremity pain may be relieved by a dorsal column stimulator.
    • A spinal cord stimulator (SCS) can be an effective treatment for the pain of RSD, including recurrent pain after ablative sympathectomy.
    • Kumar and colleagues note that the low morbidity associated with this procedure and its efficacy in patients with refractory pain related to RSD suggest that SCS is superior to ablative sympathectomy in the management of RSD.18
    • Careful evaluation is recommended before patient selection
  • Intrathecal infusion - Careful selection of patients is needed:
    • Baclofen pump - According to van Hilten and co-authors, an intrathecal (IT) Baclofen pump may be useful for treatment of dystonia in patients with RSD.19
    • Morphine pump - Intrathecal opioids should be considered carefully for chronic pain of nonmalignant origin.
    • Intrathecal bupivacaine infusion - As noted in a study by Lundborg and colleagues, this approach may alleviate the refractory pain, but it does not affect other associated symptoms or the natural course of CRPS I.20
  • Sympathectomy:
    • Radiofrequency or cryoprobe lesioning - If a sympathetic block produces significant pain relief twice, denervation with radio frequency or a cryoprobe could provide long-term relief.
    • Surgical sympathectomy - Endoscopic cervicothoracic sympathectomy could be an effective minimally invasive therapy for upper extremity RSD.
    • Chemical sympathectomy
  • Amputations:
    • Dielissen and colleagues reviewed cases of 28 patients with RSD who had amputations for intractable pain or recurrent infection, or to improve residual function.21
    • Only 2 patients were relieved of pain by amputation, and this number could not be predicted.
    • RSD recurred in the stump, especially after amputation at a level that was not free of symptoms.

Consultations

In CRPS, as in other chronic pain conditions, the high incidence of personality pathology, as noted by Monti and co-authors, may represent an exaggeration of maladaptive personality traits and coping styles resulting from chronic, intense pain.22 Such pathology can be addressed with the help of the following:

  • Evaluation - An evaluation by a psychologist is appropriate to identify the stressor and to gather information about the distress of the patient. The evaluation should consist of a structural clinical interview and a personality measure (eg, Minnesota Multiphasic Personality Scale, Hopelessness Index).
  • Psychotherapist
  • Biofeedback and counseling

Other Treatment

  • Transcutaneous electrical nerve stimulation (TENS) - According to Hassenbusch and co-authors, peripheral nerve stimulation can provide good relief for RSD when the condition is limited to the distribution of 1 major nerve.23
  • Ultrasonography
  • Superficial hot packs
  • A double-blind, prospective, multicenter trial of 416 patients by Zollinger and colleagues has shown that Vitamin C seems to reduce the prevalence of CRPS after wrist fracture. The authors recommended a daily dose of 500 mg for 50 days.24
  • Improvements in pain and bone density following intravenous administration of pamidronate, alendronate, or clodronate have been described in a few patients.

Medication

Multiple classes of medications have been tried for patients with CRPS, often with variable results and generally with limited published research to help clinicians predict which patients will respond well to a particular medication.25

Analgesic drug therapy for CRPS can be divided into the following categories:

Opioid analgesics

  • Opioids are used commonly as an analgesic for many pain syndromes.
  • Opioid therapy can be a safe and good option in patients with intractable nonmalignant pain and no history of drug abuse.
  • Quang-Cantagrel and colleagues reported that failure of one opioid cannot predict the patient's response to another opioid.26
  • High doses of tramadol may provide effective and safe relief in neuropathic pain, including allodynia.

Nonopioid analgesics (eg, NSAIDs, acetaminophen)

  • Acetaminophen is a safe choice for treatment of pain during pregnancy and breastfeeding.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) are discussed in further detail within the tables below.

Antidepressants

Antidepressant medications play a major role in treatment of neuropathic pain.

  • Tricyclic antidepressants:
    • Amitriptyline (Elavil)
    • Imipramine (Tofranil)
    • Doxepin (Sinequan)
    • Clomipramine (Anafranil)
    • Nortriptyline (Pamelor)
  • Selective serotonin reuptake inhibitor (SSRI) antidepressants:
    • Paroxetine (Paxil)
    • Fluoxetine (Prozac)
    • Sertraline (Zoloft)
    • Escitalopram (Lexapro)
  • Other antidepressants:
    • Nefazodone (Serzone)
    • Venlafaxine (Effexor)
    • Duloxetine (Cymbalta)
    • Bupropion (Wellbutrin)

Anticonvulsants

  • Sodium channel antagonists have been used in the management of neuropathic pain for several years.
  • These medications are started slowly and are administered as needed.
  • The patient is monitored carefully.
  • Use of several anticonvulsant drugs (eg, pregabalin, carbamazepine, phenytoin, sodium valproate, clonazepam, topiramate, lamotrigine) has been tried in the treatment of RSD.
  • In studies by Nicholson and by Rowbothan and colleagues, gabapentin has been reported to be effective in the management of chronic neuropathic pain syndromes.27
  • Controlled studies for the effect of lamotrigine have not become available yet, but Jain notes that the drug has shown effect in neuropathic pain.
  • Ziconotide may be useful in the future for neuropathic pain, as Jain notes that it has a favorable risk/benefit ratio, with advantages over several currently available intrathecal therapies for pain.28

Other adjunct analgesics

  • Hewitt states that N -methyl-D-aspartate (NMDA) – receptor antagonists, including ketamine and dextromethorphan, may have potential as co-analgesics when used in combination with opioids. Some studies have shown that ketamine infusion therapy provides effective pain relief and does not have adverse cognitive effects with extended use.29,30
  • Benzodiazepines, baclofen, and tizanidine may be helpful in decreasing spasm and providing pain relief.
  • Corticosteroid, mexiletine (orally active class Ib anti-arrhythmic agent), nifedipine (calcium channel blocker), propranolol (beta blocker), phenoxybenzamine (alpha blocker), and clonidine (alpha2-adrenergic agonist) are other alternatives. Some drug trials provided consistent support for analgesia with corticosteroids in the early stage and may have long-term effectiveness.
  • Lidoderm 5% patches are sometimes helpful in decreasing allodynia and providing pain relief.
  • Although it has not been approved by the Food and Drug Administration (FDA) for this indication, botulinum toxin can be considered for dystonia seen in patients with RSD.

Nonsteroidal anti-inflammatory drugs

These inhibit inflammatory reactions and pain by decreasing activity of cyclo-oxygenase, which is responsible for prostaglandin synthesis. NSAIDs may provide pain relief in the early stage of RSD.


Ibuprofen (Motrin, Advil)

NSAIDs are used commonly for patients with mild to moderate pain. Inhibit inflammatory reactions and pain by decreasing prostaglandin synthesis.

Adult

400-800 mg PO q8h; not to exceed 3200 mg/d

Pediatric

<12 years: Not recommended
>12 years: Administer as in adults

Probenecid may increase toxicity of NSAIDs; co-administration with ibuprofen may decrease effects of loop diuretics; NSAIDs may increase serum lithium levels; co-administration with anticoagulants may prolong PT

Documented hypersensitivity, active peptic ulcer disease, renal or hepatic impairment, concomitant or recent use of anticoagulants, and hemorrhagic conditions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy


Naproxen sodium (Anaprox, Naprelan, Naprosyn)

For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclo-oxygenase, which results in a decrease of prostaglandin synthesis.

Adult

275 mg PO tid or 550 mg PO bid

Pediatric

Not established

Co-administration with aspirin increases risk of inducing serious NSAID-related side effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently

Documented hypersensitivity, peptic ulcer disease, recent GI bleeding or perforation, and renal insufficiency

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with pre-existing renal disease or compromised renal perfusion risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug

Antidepressants

These drugs increase the synaptic concentration of serotonin and/or norepinephrine in the CNS by inhibiting their re-uptake by the presynaptic neuronal membrane. Similar agents that can be helpful are duloxetine (Cymbalta) and venlafaxine (Effexor).


Nortriptyline (Pamelor)

Has demonstrated effectiveness in the treatment of chronic and neuropathic pain.

Adult

25-100 mg PO hs; not to exceed 200 mg/d

Pediatric

Children: 0.1 mg/kg PO hs initial dose; increase as tolerated, up to 0.5-2 mg/d hs
Adolescents: 25-50 mg/d PO; increase gradually to 100 mg/d

Co-administration with aspirin increases risk of inducing serious NSAID-related side effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently

Documented hypersensitivity, peptic ulcer disease, recent GI bleeding or perforation, and renal insufficiency; patient who has received MAOI therapy within past 14 d

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with pre-existing renal disease or compromised renal perfusion risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug


Amitriptyline (Elavil)

Has demonstrated effectiveness in certain chronic and neuropathic pain.

Adult

25-100 mg PO hs; not to exceed 150 mg/d

Pediatric

Not established

Phenobarbital may decrease effects; co-administration with CYP2D6 enzyme system inhibitors (eg, cimetidine, quinidine) may increase amitriptyline levels; inhibits hypotensive effects of guanethidine; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram

Documented hypersensitivity; patient who has taken MAOIs in past 14 d; history of seizures, cardiac arrhythmias, glaucoma, and urinary retention

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in cardiac conduction disturbances and history of hyperthyroidism or renal or hepatic impairment; avoid use in elderly patients


Duloxetine (Cymbalta)

Indicated for diabetic peripheral neuropathic pain. Potent inhibitor of neuronal serotonin and norepinephrine reuptake.

Adult

60 mg PO qd; may initiate with lower dose in patient unable to tolerate 60 mg/d

Pediatric

Not established

Metabolized by CYP1A2 and CYP2D6; co-administration with drugs that inhibit CYP1A2 (eg, fluvoxamine, cimetidine, ciprofloxacin, enoxacin) may increase duloxetine blood levels and toxicity; co-administration with drugs that inhibit CYP2D6 (eg, paroxetine, fluoxetine, quinidine) may increase duloxetine blood levels and toxicity; duloxetine moderately inhibits CYP2D6 and may decrease elimination of CYP2D6 substrates (eg, tricyclic antidepressants, phenothiazines [eg, thioridazine], type-1C anti-arrhythmics [eg, propafenone, flecainide]); co-administration with MAO inhibitors or triptans can cause serotonin syndrome consisting of serious, sometimes fatal reactions that include hyperthermia, rigidity, myoclonus, autonomic instability, mental status changes (including extreme agitation, delirium, and coma) (see contraindications)

Documented hypersensitivity; uncontrolled narrow-angle glaucoma; within 14 d of stopping MAO inhibitor use (do not initiate MAO inhibitors within 5 d of stopping duloxetine)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Observe closely for clinical worsening and suicidality when initiating treatment or following dosage change; gradually decrease dose when discontinuing, do not abruptly discontinue; caution with hepatic impairment or end-stage renal disease; recommended not to prescribe to patients with substantial alcohol use or evidence of chronic liver disease; may cause slight blood pressure increase; may activate mania or hypomania; common adverse effects include nausea, dry mouth, constipation, dyspepsia, gastritis, loose stools, decreased appetite, fatigue, somnolence and increased sweating; may cause serotonin syndrome (ie, changes in mental status [agitation, hallucinations, coma], autonomic instability [tachycardia, labile blood pressure, hyperthermia], neuromuscular abnormalities [hyperreflexia, incoordination])

Anticonvulsants

Use of certain anti-epileptic drugs, such as the GABA analogue gabapentin (Neurontin), has proven helpful in some cases of neuropathic pain. Other anticonvulsant drugs (eg, carbamazepine, phenytoin, sodium valproate or clonazepam, topiramate, lamotrigine, zonisamide, tiagabine) also have been tried in RSD.


Gabapentin (Neurontin)

Has anticonvulsant properties and antineuralgic effects; however, exact mechanism of action is unknown. Structurally related to GABA but does not interact with GABA receptors.

Adult

100 mg PO hs to 1200 mg PO tid

Pediatric

<12 years: Not recommended
>12 years: Administer as in adults

Antacids may reduce bioavailability of gabapentin significantly (administer at least 2 h following antacids); may increase norethindrone levels significantly

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Abrupt withdrawal of this medication may precipitate seizures; caution in severe renal disease


Pregabalin (Lyrica)

Structural derivative of GABA. Mechanism of action unknown. Binds with high affinity to alpha 2 -delta site (a calcium channel subunit). In vitro, reduces calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. FDA approved for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures.

Adult

50 mg PO tid initially; if needed, may increase to 100 mg tid within 1 wk

Pediatric

Not established

May cause additive effects on cognitive and gross motor functioning when co-administered with drugs that cause dizziness or somnolence

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Discontinue gradually (over a minimum of 1 wk) to minimize increased seizure frequency in patients with seizure disorders; may cause insomnia, nausea, headache, or diarrhea with abrupt withdrawal; common adverse effects include dizziness, somnolence, blurred vision, weight gain, and peripheral edema; may elevate creatinine kinase level, decrease platelet count, and increase PR interval; doses >300 mg/d associated with higher rate of adverse effects and treatment discontinuation; decrease dose with renal impairment (ie, CrCl <60 mL/min); angio-edema has been reported during postmarketing surveillance

Opioid analgesics

These commonly used analgesics are employed for many pain syndromes.


Oxycodone (OxyContin)

Currently, the long-acting form of opioids is commonly used in initial and later stages of RSD. Start with a small dose and increase gradually.

Adult

10-160 mg PO q12h

Pediatric

<12 years: Not established
>12 years: Administer as in adults

May increase the CNS depressant effect of other drugs, including alcohol, antihistamines, antidepressants, sedative/hypnotics, and MAOIs

Documented hypersensitivity; presence of intracranial lesion associated with impaired intracranial pressure (hydromorphone); patients receiving MAOIs or recent use of MAOIs; poor respiratory function (eg, COPD, cor pulmonale, emphysema, status asthmaticus, kyphoscoliosis)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in impaired respiratory and cardiac function; caution in severe renal disease


Morphine sulfate (MS Contin, Avinza, Kadian, Duramorph, Astramorph)

DOC for analgesia due to reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Various IV doses are used; commonly titrated until desired effect obtained.

Adult

Starting dose: 0.1 mg/kg IV/IM/SC
Maintenance dose: 5-20 mg/70 kg IV/IM/SC q4h
Relatively hypovolemic patients: Start with 2 mg IV/IM/SC; re-assess hemodynamic effects of dose

Pediatric

Infants and children: 0.1-0.2 mg/kg dose IV/IM/SC q2-4h prn; not to exceed 15 mg/dose; may initiate at 0.05 mg/kg/dose

Phenothiazines may antagonize analgesic effects of opiate agonists; tricyclic antidepressants, MAOIs, and other CNS depressants may potentiate adverse effects of morphine

Documented hypersensitivity; hypotension; potentially compromised airway where establishing rapid airway control would be difficult

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hypotension, respiratory depression, nausea, emesis, constipation, and urinary retention; caution in atrial flutter and other supraventricular tachycardias; has vagolytic action and may increase ventricular response rate


Fentanyl transdermal patch (Duragesic)

Potent narcotic analgesic with much shorter half-life than morphine sulfate. Excellent choice for pain management and sedation with short duration (30-60 min) and easy to titrate. Easily and quickly reversed by naloxone.
When using transdermal dosage form, most patients are controlled with 72 h dosing intervals; however, some patients may require dosing intervals of 48 h.

Adult

12 mcg/h, q48-72h
25 mcg/h (10 cm2), q48-72h
50 mcg/h (20 cm2), q48-72h
75 mcg/h (75 cm2), q48-72h
100 mcg/h (100 cm2), q48-72h

Pediatric

Not established

Phenothiazines may antagonize analgesic effects of opiate agonists; tricyclic antidepressants may potentiate adverse effects of fentanyl when both drugs are used concurrently

Documented hypersensitivity,
hypotension, and potentially compromised airway

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with hypotension, respiratory depression, constipation, nausea, emesis, and urinary retention; idiosyncratic reaction, known as chest wall rigidity syndrome, may require neuromuscular blockade in order to increase ventilation

More on Complex Regional Pain Syndromes

Overview: Complex Regional Pain Syndromes
Differential Diagnoses & Workup: Complex Regional Pain Syndromes
Treatment & Medication: Complex Regional Pain Syndromes
Follow-up: Complex Regional Pain Syndromes
Multimedia: Complex Regional Pain Syndromes
References
Further Reading
[ CLOSE WINDOW ]

References

  1. Paice E. Reflex sympathetic dystrophy. BMJ. Jun 24 1995;310(6995):1645-8. [Medline]. [Full Text].

  2. Uceyler N, Eberle T, Rolke R, et al. Differential expression patterns of cytokines in complex regional pain syndrome. Pain. Sep 2007;[Medline].

  3. Wasner G, Heckmann K, Maier C, et al. Vascular abnormalities in acute reflex sympathetic dystrophy (CRPS I): complete inhibition of sympathetic nerve activity with recovery. Arch Neurol. May 1999;56(5):613-20. [Medline]. [Full Text].

  4. Kurvers HA, Jacobs MJ, Beuk RJ, et al. The spinal component to skin blood flow abnormalities in reflex sympathetic dystrophy. Arch Neurol. Jan 1996;53(1):58-65. [Medline].

  5. Blaes F, Tschernatsch M, Braeu ME, Matz O, Schmitz K, Nascimento D. Autoimmunity in complex-regional pain syndrome. Ann N Y Acad Sci. Jun 2007;1107:168-73. [Medline].

  6. Veldman PH, Reynen HM, Arntz IE, Goris RJ. Signs and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients. Lancet. Oct 23 1993;342(8878):1012-6. [Medline].

  7. Maleki J, LeBel AA, Bennett GJ, et al. Patterns of spread in complex regional pain syndrome, type I (reflex sympathetic dystrophy). Pain. Dec 1 2000;88(3):259-66. [Medline].

  8. Peterlin BL, Rosso AL, Nair S, et al. Migraine may be a risk factor for the development of complex regional pain syndrome. Cephalalgia. Jul 9 2009;[Medline].

  9. Werner R, Davidoff G, Jackson MD, et al. Factors affecting the sensitivity and specificity of the three-phase technetium bone scan in the diagnosis of reflex sympathetic dystrophy syndrome in the upper extremity. J Hand Surg [Am]. May 1989;14(3):520-3. [Medline].

  10. Kozin F, Soin JS, Ryan LM, et al. Bone scintigraphy in the reflex sympathetic dystrophy syndrome. Radiology. Feb 1981;138(2):437-43. [Medline]. [Full Text].

  11. Schürmann M, Zaspel J, Löhr P, et al. Imaging in early posttraumatic complex regional pain syndrome: a comparison of diagnostic methods. Clin J Pain. Jun 2007;23(5):449-57. [Medline].

  12. Bruehl S, Lubenow TR, Nath H, Ivankovich O. Validation of thermography in the diagnosis of reflex sympathetic dystrophy. Clin J Pain. Dec 1996;12(4):316-25. [Medline].

  13. Chelimsky TC, Low PA, Naessens JM, et al. Value of autonomic testing in reflex sympathetic dystrophy. Mayo Clin Proc. Nov 1995;70(11):1029-40. [Medline].

  14. Brunnekreef JJ, Oosterhof J, Wolff AP, et al. No impaired hemoglobin oxygenation in forearm muscles of patients with chronic CRPS-1. Clin J Pain. Jul-Aug 2009;25(6):513-9. [Medline].

  15. Rashiq S, Galer BS. Proximal myofascial dysfunction in complex regional pain syndrome: a retrospective prevalence study. Clin J Pain. Jun 1999;15(2):151-3. [Medline].

  16. Steverens VL, Oerlemans HM, Weesels A. Cost effectiveness analysis of adjuring physical or occupational therapy for patients with RSD. Arch Phys Med Rehabilitation. 1999;80:1038-43.

  17. Johnston EC, Howell SJ. Tension neuropathy of the superficial peroneal nerve: associated conditions and results of release. Foot Ankle Int. Sep 1999;20(9):576-82. [Medline].

  18. Kumar K, Nath RK, Toth C. Spinal cord stimulation is effective in the management of reflex sympathetic dystrophy. Neurosurgery. Mar 1997;40(3):503-8; discussion 508-9. [Medline].

  19. van Hilten BJ, van de Beek WJ, Hoff JI, et al. Intrathecal baclofen for the treatment of dystonia in patients with reflex sympathetic dystrophy. N Engl J Med. Aug 31 2000;343(9):625-30. [Medline]. [Full Text].

  20. Lundborg C, Dahm P, Nitescu P, et al. Clinical experience using intrathecal (IT) bupivacaine infusion in three patients with complex regional pain syndrome type I (CRPS-I). Acta Anaesthesiol Scand. Jul 1999;43(6):667-78. [Medline].

  21. Dielissen PW, Claassen AT, Veldman PH, Goris RJ. Amputation for reflex sympathetic dystrophy. J Bone Joint Surg Br. Mar 1995;77(2):270-3. [Medline]. [Full Text].

  22. Monti DA, Herring CL, Schwartzman RJ, et al. Personality assessment of patients with complex regional pain syndrome type I. Clin J Pain. Dec 1998;14(4):295-302. [Medline].

  23. Hassenbusch SJ, Stanton-Hicks M, Schoppa D, et al. Long-term results of peripheral nerve stimulation for reflex sympathetic dystrophy. J Neurosurg. Mar 1996;84(3):415-23. [Medline].

  24. Zollinger PE, Tuinebreijer WE, Breederveld RS, et al. Can vitamin C prevent complex regional pain syndrome in patients with wrist fractures? A randomized, controlled, multicenter dose-response study. J Bone Joint Surg Am. Jul 2007;89(7):1424-31. [Medline].

  25. Hsu ES. Practical management of complex regional pain syndrome. Am J Ther. Mar-Apr 2009;16(2):147-54. [Medline].

  26. Quang-Cantagrel ND, Wallace MS, Magnuson SK. Opioid substitution to improve the effectiveness of chronic noncancer pain control: a chart review. Anesth Analg. Apr 2000;90(4):933-7. [Medline]. [Full Text].

  27. Rowbotham M, Harden N, Stacey B, et al. Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. JAMA. Dec 2 1998;280(21):1837-42. [Medline].

  28. Jain KK. An evaluation of intrathecal ziconotide for the treatment of chronic pain. Expert Opin Investig Drugs. Oct 2000;9(10):2403-10. [Medline].

  29. Kiefer RT, Rohr P, Ploppa A, et al. Complete recovery from intractable complex regional pain syndrome, CRPS-type I, following anesthetic ketamine and midazolam. Pain Pract. Jun 2007;7(2):147-50. [Medline].

  30. Koffler SP, Hampstead BM, Irani F, et al. The neurocognitive effects of 5 day anesthetic ketamine for the treatment of refractory complex regional pain syndrome. Arch Clin Neuropsychol. Aug 2007;22(6):719-29. [Medline].

  31. Dumitru D. Reflex sympathetic dystrophy. Phys Med Rehabil: State Art Rev. 1991;5:89-101.

  32. Baron R. Peripheral neuropathic pain: from mechanisms to symptoms. Clin J Pain. Jun 2000;16(2 Suppl):S12-20. [Medline].

  33. Baron R, Maier C. Reflex sympathetic dystrophy: skin blood flow, sympathetic vasoconstrictor reflexes and pain before and after surgical sympathectomy. Pain. Oct 1996;67(2-3):317-26. [Medline].

  34. Bhatia KP, Bhatt MH, Marsden CD. The causalgia-dystonia syndrome. Brain. Aug 1993;116 ( Pt 4):843-51. [Medline].

  35. Blanchard J, Ramamurthy S, Walsh N, et al. Intravenous regional sympatholysis: a double-blind comparison of guanethidine, reserpine, and normal saline. J Pain Symptom Manage. Dec 1990;5(6):357-61. [Medline].

  36. Brown DL. Somatic or sympathetic block for reflex sympathetic dystrophy. Which is indicated?. Hand Clin. Aug 1997;13(3):485-97. [Medline].

  37. Bruehl S, Harden RN, Galer BS, et al. External validation of IASP diagnostic criteria for Complex Regional Pain Syndrome and proposed research diagnostic criteria. International Association for the Study of Pain. Pain. May 1999;81(1-2):147-54. [Medline].

  38. Clinchot DM, Lorch F. Sympathetic skin response in patients with reflex sympathetic dystrophy. Am J Phys Med Rehabil. Jul-Aug 1996;75(4):252-6.

  39. Cohen JS. Erythromelalgia: new theories and new therapies. J Am Acad Dermatol. Nov 2000;43(5 Pt 1):841-7. [Medline].

  40. Davis MD, O'Fallon WM, Rogers RS 3rd, Rooke TW. Natural history of erythromelalgia: presentation and outcome in 168 patients. Arch Dermatol. Mar 2000;136(3):330-6. [Medline]. [Full Text].

  41. Galer BS, Bruehl S, Harden RN. IASP diagnostic criteria for complex regional pain syndrome: a preliminary empirical validation study. International Association for the Study of Pain. Clin J Pain. Mar 1998;14(1):48-54. [Medline].

  42. [Best Evidence] Goldstein DJ, Lu Y, Detke MJ, et al. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain. Jul 2005;116(1-2):109-18. [Medline].

  43. Harden RN. A clinical approach to complex regional pain syndrome. Clin J Pain. Jun 2000;16(2 Suppl):S26-32. [Medline].

  44. Hewitt DJ. The use of NMDA-receptor antagonists in the treatment of chronic pain. Clin J Pain. Jun 2000;16(2 Suppl):S73-9. [Medline].

  45. Hopp J, Schwartzman RJ, Grothusen J. Increased sensory thresholds in patients with reflex sympathetic dystrophy. Neurology. Feb 1996;46 A:227.

  46. Hord ED, Oaklander AL. Complex regional pain syndrome: a review of evidence-supported treatment options. Curr Pain Headache Rep. Jun 2003;7(3):188-96. [Medline].

  47. Kemler MA, Barendse GA, van Kleef M, et al. Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy. N Engl J Med. Aug 31 2000;343(9):618-24. [Medline]. [Full Text].

  48. Kemler MA, van de Vusse AC, van den Berg-Loonen EM, et al. HLA-DQ1 associated with reflex sympathetic dystrophy. Neurology. Oct 12 1999;53(6):1350-1. [Medline].

  49. Kingery WS. A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes. Pain. Nov 1997;73(2):123-39. [Medline].

  50. Kurvers HA, Jacobs MJ, Beuk RJ, et al. Reflex sympathetic dystrophy: evolution of microcirculatory disturbances in time. Pain. Mar 1995;60(3):333-40. [Medline].

  51. Linson MA, Leffert R, Todd DP. The treatment of upper extremity reflex sympathetic dystrophy with prolonged continuous stellate ganglion blockade. J Hand Surg [Am]. Mar 1983;8(2):153-9. [Medline].

  52. Merskey H, Bogduk N. Classification of Chronic Pain, Description of Chronic Pain Syndrome and Definitions of Pain Terms. Seattle, Wash: IASP Press; 1994.

  53. Norton JV, Zager E, Grady JF. Erythromelalgia: diagnosis and classification. J Foot Ankle Surg. May-Jun 1999;38(3):238-41. [Medline].

  54. Ochoa JL. Reflex sympathetic dystrophy: a disease of medical understanding. Clin J Pain. Dec 1992;8(4):363-6; discussion 367-9. [Medline].

  55. Pak TJ, Martin GM, Magness JL, et al. Reflex sympathetic dystrophy. Review of 140 cases. Minn Med. May 1970;53(5):507-12. [Medline].

  56. Portenoy RK, Foley KM. Chronic use of opioid analgesics in non-malignant pain: report of 38 cases. Pain. May 1986;25(2):171-86. [Medline].

  57. Rommel O, Tegenthoff M, Pern U, et al. Sympathetic skin response in patients with reflex sympathetic dystrophy. Clin Auton Res. Sep 1995;5(4):205-10. [Medline].

  58. Schwartzman RJ. Explaining reflex sympathetic dystrophy. Arch Neurol. May 1999;56(5):521-2. [Medline].

  59. Schwartzman RJ. New treatments for reflex sympathetic dystrophy. N Engl J Med. Aug 31 2000;343(9):654-6. [Medline].

  60. Schwartzman RJ, Kerrigan J. The movement disorder of reflex sympathetic dystrophy. Neurology. Jan 1990;40(1):57-61. [Medline].

  61. Schwartzman RJ, Liu JE, Smullens SN, et al. Long-term outcome following sympathectomy for complex regional pain syndrome type 1 (RSD). J Neurol Sci. Sep 10 1997;150(2):149-52. [Medline].

  62. Schwartzman RJ, Maleki J. Postinjury neuropathic pain syndromes. Med Clin North Am. May 1999;83(3):597-626. [Medline].

  63. Stanton-Hicks M, Baron R, Boas R, et al. Complex regional pain syndromes: guidelines for therapy. Clin J Pain. Jun 1998;14(2):155-66. [Medline].

  64. Stanton-Hicks M, Janig W, Hassenbusch S, et al. Reflex sympathetic dystrophy: changing concepts and taxonomy. Pain. Oct 1995;63(1):127-33. [Medline].

  65. Tahmoush AJ, Schwartzman RJ, Hopp JL, et al. Quantitative sensory studies in complex regional pain syndrome type 1/RSD. Clin J Pain. Dec 2000;16(4):340-4. [Medline].

  66. van der Laan L, Veldman PH, Goris RJ. Severe complications of reflex sympathetic dystrophy: infection, ulcers, chronic edema, dystonia, and myoclonus. Arch Phys Med Rehabil. Apr 1998;79(4):424-9. [Medline].

  67. Wasner G, Backonja MM, Baron R. Traumatic neuralgias: complex regional pain syndromes (reflex sympathetic dystrophy and causalgia): clinical characteristics, pathophysiological mechanisms and therapy. Neurol Clin. Nov 1998;16(4):851-68. [Medline].

  68. Wechsler RJ, Frank ED, Halpern EH, et al. Percutaneous lumbar sympathetic plexus catheter placement for short- and long-term pain relief: CT technique and results. J Comput Assist Tomogr. Jul-Aug 1998;22(4):518-23. [Medline].

  69. Wilder RT, Berde CB, Wolohan M, et al. Reflex sympathetic dystrophy in children. Clinical characteristics and follow-up of seventy patients. J Bone Joint Surg Am. Jul 1992;74(6):910-9. [Medline].

  70. Zollinger PE, Tuinebreijer WE, Kreis RW, et al. Effect of vitamin C on frequency of reflex sympathetic dystrophy in wrist fractures: a randomised trial. Lancet. Dec 11 1999;354(9195):2025-8. [Medline].

[ CLOSE WINDOW ]

Keywords

complex regional pain syndrome, CRPS, RSD, regional pain syndrome, reflex sympathetic dystrophy, reflex sympathetic dystrophy syndrome, RSD symptoms, RSD CRPS, RSD pain, RSD treatment, causalgia, complex regional pain syndrome I, CRPS I, complex regional pain syndrome II, CRPS II, mimo-causalgia, Sudeck atrophy of bone, shoulder-hand syndrome, algoneurodystrophy, reflex dystrophy, reflex neurovascular dystrophy

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Manish K Singh, MD, Assistant Professor, Department of Neurology, Teaching Faculty for Pain Management and Neurology Residency Program, Hahnemann University Hospital, Drexel College of Medicine; Medical Director, Neurology and Pain Management, Jersey Institute of Neuroscience
Manish K Singh, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pain Medicine, American Association of Physicians of Indian Origin, American Headache Society, American Medical Association, and American Society of Regional Anesthesia and Pain Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Jashvant Patel, MD, Medical Director, Department of Pain Medicine and Comprehensive Rehabilitation, Medical College of Pennsylvania Hahnemann University
Jashvant Patel, MD is a member of the following medical societies: Alberta Medical Association, American Academy of Pain Medicine, American Academy of Physical Medicine and Rehabilitation, American Medical Association, American Society of Regional Anesthesia and Pain Medicine, and Medical Society of the State of New York
Disclosure: Nothing to disclose.

John Grothusen, PhD, Director of Quantitative Sensory and Autonomic Nervous System Laboratory, Assistant Professor, Department of Neurology, MCP Hahnemann University
Disclosure: Nothing to disclose.

Patrick M Foye, MD, FAAPMR, FAAEM, Associate Professor of Physical Medicine and Rehabilitation, Co-Director of Musculoskeletal Fellowship, Co-Director of Back Pain Clinic, Director of Coccyx Pain Service (Tailbone Pain Service: www.TailboneDoctor.com), University of Medicine and Dentistry of New Jersey, New Jersey Medical School
Patrick M Foye, MD, FAAPMR, FAAEM is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine, Association of Academic Physiatrists, and International Spine Intervention Society
Disclosure: Nothing to disclose.

Medical Editor

Robert J Kaplan, MD, James E Van Zandt VA Medical Center, Staff Physician, Department of Rehabilitation Medicine
Robert J Kaplan, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, Association of Academic Physiatrists, and Physiatric Association of Spine, Sports and Occupational Rehabilitation
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Patrick M Foye, MD, FAAPMR, FAAEM, Associate Professor of Physical Medicine and Rehabilitation, Co-Director of Musculoskeletal Fellowship, Co-Director of Back Pain Clinic, Director of Coccyx Pain Service (Tailbone Pain Service: www.TailboneDoctor.com), University of Medicine and Dentistry of New Jersey, New Jersey Medical School
Patrick M Foye, MD, FAAPMR, FAAEM is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine, Association of Academic Physiatrists, and International Spine Intervention Society
Disclosure: Nothing to disclose.

CME Editor

Kelly L Allen, MD, Regional Medical Director, IMX-Medical Management Services
Disclosure: Nothing to disclose.

Chief Editor

Rene Cailliet, MD, Professor-Chairman Emeritus, Department of Rehabilitation Medicine, University of Southern California School of Medicine; Former Director, Department of Rehabilitation Medicine, Santa Monica Hospital Medical Center
Rene Cailliet, MD is a member of the following medical societies: American Academy of Pain Medicine, American Academy of Physical Medicine and Rehabilitation, American Pain Society, Association of American Medical Colleges, International Association for the Study of Pain, and Pan American Medical Association
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.