What is the treatment for Complex Regional Pain Syndrome (CRPS) in a patient with a history of Spinal Cord Injury (SCI)?

Treatment of Complex Regional Pain Syndrome in Patients with Spinal Cord Injury

Treatment should begin with gabapentinoids (pregabalin or gabapentin) or tricyclic antidepressants (amitriptyline) as first-line therapy, combined with immediate physical therapy, and if conservative management fails after 3-6 months, proceed to spinal cord stimulation following a mandatory trial period. 1, 2, 3

First-Line Pharmacological Management

Initiate gabapentinoids as the primary oral medication:

• Start gabapentin titrated to 2400 mg daily in divided doses, or use pregabalin as an alternative 1, 3
• These medications are recommended by the American College of Physicians as first-line treatment for neuropathic pain following spinal cord injury 1, 3

Alternatively, use tricyclic antidepressants:

• Begin amitriptyline at 10-25 mg/day, particularly in patients over 40 years 1, 3
• Obtain baseline ECG screening before starting amitriptyline in patients over 40 due to cardiac risks 1, 3
• Monitor for anticholinergic side effects including dry mouth, orthostatic hypotension, constipation, and urinary retention 3

For inadequate response to monotherapy:

• Combine gabapentinoid with tricyclic antidepressant (amitriptyline) for enhanced pain control 3
• The French medical society recommends introducing oral gabapentinoid treatment for more than 6 months in association with tricyclic antidepressants or serotonin reuptake inhibitors when monotherapy is inefficient 4

Multimodal Analgesia During Acute Phase

Implement multimodal analgesia during surgical management:

• Combine non-opioid analgesics, antihyperalgesic drugs (ketamine), and opioids to prevent prolonged pain 4
• This approach is recommended during the acute phase to reduce the occurrence of chronic neuropathic pain 4

Physical Therapy as Cornerstone Treatment

Physical therapy is the cornerstone and first-line treatment for CRPS and must begin immediately upon medical stability:

• Implement gentle stretching, mobilization techniques, and active range of motion exercises specifically targeting the affected limb 2, 5
• Stretching should be performed for at least 20 minutes per zone, completed by simple posture orthosis 4
• Early, vigorous, and consistent rehabilitation practices maximize neurological recovery 4

A critical pitfall: Delaying physical therapy while waiting for pain control will worsen outcomes. Pain medications should enable participation in physical therapy, not replace it 5.

Adjunctive Topical Treatments

Consider topical treatments for localized pain:

• Use topical compounded creams containing amitriptyline for neuropathic pain management 3
• A combination of topical baclofen, amitriptyline, and ketamine gel has shown effectiveness after 4 weeks 3
• Topical treatments have minimal systemic effects, making them suitable for patients who cannot tolerate oral medications 3

Interventional Procedures for Moderate to Severe Cases

Sympathetic nerve blocks are first-line interventional treatments:

• Perform stellate ganglion blocks for upper extremity CRPS 6
• Perform lumbar sympathetic blocks for lower extremity CRPS 6
• Sympathetic blocks may be considered to support the diagnosis of sympathetically maintained pain 4
• Use these blocks to enable participation in physical therapy when pain is too severe 5

Ketamine Infusion for Refractory Cases

Reserve ketamine infusion as second-line or rescue therapy:

• Use a 5-day inpatient ketamine infusion protocol at subanesthetic doses of 0.1-0.35 mg/kg/h, administered over 6 hours daily 1
• This provides the best balance between pain control and side effects 1
• Ketamine is particularly beneficial for CRPS patients with central sensitization and "clinical wind-up" 1

Critical safety considerations:

• Use extreme caution in elderly patients due to significant risk of postoperative confusion and delirium 1
• Monitor respiratory parameters closely, as concomitant use with opioids, benzodiazepines, or other CNS depressants may result in profound sedation and respiratory depression 1
• Ketamine treatment should not delay or interrupt the comprehensive rehabilitation protocol 1

Spinal Cord Stimulation for Refractory CRPS

Spinal cord stimulation should be considered if no response to conservative treatment is noted within 12-16 weeks:

• SCS has been shown to be highly effective in CRPS type I, resulting in significant, long-term reduction in pain and improvement in quality of life 7
• The American Society of Anesthesiologists recommends SCS for CRPS patients who have not responded to other therapies 4, 2

Mandatory prerequisites before SCS approval:

• Document failure of physical therapy with specific mobilization techniques 2
• Document failure of first-line analgesics (acetaminophen, NSAIDs) with inadequate response or intolerable side effects 2
• Document failure of neuropathic pain medications (gabapentinoids, tricyclic antidepressants, or SNRIs) with specific dosages, duration, and reasons for discontinuation 2
• Consider sympathetic blocks to determine if sympathetically maintained pain is present 2

Required trial period:

• A temporary spinal cord stimulation trial must be performed before permanent implantation 4, 2
• The trial must demonstrate adequate pain relief (typically >50% reduction) and measurable functional improvement 2
• Proceeding directly to permanent implantation without a trial will result in denial 2

Critical safety exclusions:

• Rule out coagulopathy and address anticoagulation/antiplatelet therapy with appropriate perioperative management 2
• Exclude active infection, as infection risk is 10-29% 2
• Obtain mandatory psychological evaluation to identify untreated psychiatric comorbidity or substance abuse that would predict poor outcomes 2

SCS is particularly effective when applied early in the course of the disease, helping to restore function in affected extremities 7. Despite a relatively high complication rate (28% in one series requiring revision surgery), SCS remains the best choice for pain reduction management in refractory CRPS patients 8.

Alternative Therapies for Refractory Pain

Medical cannabis may be considered for appropriate patients:

• Cannabis oil may be effective for neuropathic pain, though evidence quality is moderate 3
• Start with low doses and titrate slowly, monitoring for neuropsychiatric effects 3
• Benefits must be balanced against potential risks including neuropsychiatric adverse effects, lung damage from smoked forms, and addiction risk 3

Treatment Algorithm Summary

Step 1 (Immediate): Begin gabapentinoid (gabapentin 2400 mg/day) or amitriptyline (10-25 mg/day) plus immediate physical therapy 1, 3, 5

Step 2 (If inadequate response): Add topical treatments (compounded amitriptyline cream) or combine gabapentinoid with tricyclic antidepressant 3

Step 3 (Moderate to severe pain): Add sympathetic nerve blocks to enable physical therapy participation 5, 6

Step 4 (Refractory after 12-16 weeks): Consider ketamine infusion (5-day protocol) or proceed to SCS trial 1, 7

Step 5 (Failed conservative management after 3-6 months): Proceed to permanent SCS implantation if trial successful 2, 7

A critical pitfall: Delaying interventional procedures like SCS adversely affects treatment response. Early intervention is needed to achieve pain relief, functional restoration, and psychological stabilization 7, 5, 8.