Can Calcitonin Gene-Related Peptide (CGRP) inhibitors, such as erenumab (erenumab), be used to treat Complex Regional Pain Syndrome (CRPS)?

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Last updated: December 17, 2025View editorial policy

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CGRP Inhibitors Should Not Be Used for Complex Regional Pain Syndrome

CGRP inhibitors such as erenumab have no role in treating CRPS and should not be used—these medications are FDA-approved and guideline-recommended exclusively for migraine prevention, not for neuropathic pain syndromes. 1

Why CGRP Inhibitors Are Not Appropriate for CRPS

  • No evidence exists supporting CGRP inhibitor use in CRPS, and established guideline-based treatments with proven efficacy should be used instead 1
  • CGRP inhibitors (erenumab, fremanezumab, galcanezumab, eptinezumab) are specifically indicated only for episodic and chronic migraine prevention 2
  • The mechanism of action—blocking CGRP receptors to prevent migraine attacks—does not address the complex pathophysiology of CRPS, which involves inflammatory, neuropathic, and sympathetically-mediated pain components 3

Evidence-Based Treatment Algorithm for CRPS

Immediate Initiation (All Patients, <3 Months)

  • Start physical therapy immediately with gentle stretching and active range of motion exercises—this is the cornerstone of CRPS management regardless of other interventions 1, 4, 5
  • Initiate acetaminophen or ibuprofen (if no contraindications) for pain control to enable participation in physical therapy 1, 4
  • Consider short-course oral corticosteroids (30-50 mg daily for 3-5 days, then taper over 1-2 weeks) to reduce swelling and pain in early CRPS 1, 4, 6, 7

Persistent CRPS (3-6 Months)

  • Continue physical therapy as the foundation of treatment 5
  • Consider sympathetic blocks (stellate ganglion or lumbar sympathetic blocks) when there is consistent improvement and increasing duration of pain relief with each successive block 1, 4
  • These blocks should only be used as components of multimodal treatment, not as monotherapy 4
  • Intranasal or intramuscular calcitonin may provide benefit despite some contradictory evidence 6, 7
  • Intravenous bisphosphonates show clear benefits and should be considered 6, 8

Refractory CRPS (>6 Months)

  • Spinal cord stimulation should be considered after failure of conservative therapies, with a trial performed before permanent implantation 1, 4, 6
  • Implement TENS as part of a multimodal approach to pain management 1, 4
  • Consider gabapentin for neuropathic pain component 7, 8
  • Botulinum toxin injections into affected muscles when pain is related to spasticity 4

Critical Pitfalls to Avoid

  • Never delay physical therapy waiting for pain to resolve—this worsens outcomes through disuse and pain upregulation 5
  • Do not use CGRP inhibitors or other unproven therapies when evidence-based options exist 1
  • Avoid continuing sympathetic blocks indefinitely without documented progressive improvement and increasing duration of relief 4
  • Do not use sympathetic blocks for non-CRPS neuropathic pain—this contradicts evidence-based guidelines 4
  • Avoid sympathectomy, which has a high likelihood of adverse outcomes without proven efficacy 6
  • Do not use peripheral somatic nerve blocks for long-term treatment of chronic pain 4

Monitoring Requirements

  • Document objective functional outcomes beyond pain scores, including activities of daily living, cognitive function, autonomic stability, and temperature dysregulation 4
  • Evaluate patients at least twice annually by a specialist due to high recurrence risk 5
  • For sympathetic blocks, record duration of relief with each successive block to demonstrate the required pattern of "increasing duration" 4

References

Guideline

CGRP Inhibitors and Established Treatments for Complex Regional Pain Syndrome (CRPS)

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Treatment of Complex Regional Pain Syndrome (CRPS)

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Complex Regional Pain Syndrome Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Complex regional pain syndrome: which treatments show promise?

The Journal of family practice, 2005

Research

Pharmacotherapy options for complex regional pain syndrome.

Expert review of neurotherapeutics, 2007

Research

Treatment of complex regional pain syndrome: a review of the evidence.

Canadian journal of anaesthesia = Journal canadien d'anesthesie, 2010

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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