Intravenous Ketamine for Complex Regional Pain Syndrome (CRPS): A Promising Option for Refractory Pain

Intravenous Ketamine for Complex Regional Pain Syndrome (CRPS): A Promising Option for Refractory Pain

By Pradeep Chopra, MD

Complex Regional Pain Syndrome (CRPS) is a debilitating neuropathic pain condition characterized by disproportionate pain, sensory abnormalities, autonomic changes, and functional impairment. Intravenous (IV) ketamine infusion therapy has emerged as a valuable option.

What Is Ketamine?

Ketamine in sub-anesthetic doses, it modulates central sensitization and reduces the amplification of pain signals within the central nervous system—a key mechanism in CRPS.

How Does It Work for CRPS?

CRPS is thought to involve excessive NMDA receptor activation, contributing to central sensitization, allodynia, and hyperalgesia. Ketamine's ability to block NMDA receptors and reset abnormal pain signaling pathways makes it uniquely suited for treating this condition.

Additional benefits include:

·       - Anti-inflammatory effects via inhibition of microglial activation.

·       - Enhanced descending pain inhibition through modulation of monoaminergic pathways.

·       - Rapid onset of analgesia for certain patients.

Evidence Supporting Ketamine in CRPS

While research is ongoing, multiple studies and case series support its efficacy:
- Schwartzman et al. (2009) reported sustained pain relief in CRPS patients who underwent a 4-day ketamine infusion protocol, with benefits lasting weeks to months.
- Sigtermans et al. (2009, *Pain*), in a double-blind placebo-controlled trial, showed that low-dose ketamine resulted in significant pain reduction, though functional improvement was limited.
- Kirkpatrick et al. have also documented safety and long-term benefits in selected patients using repeated infusion protocols.

Clinical Use: What Patients Should Know

·       - Eligibility: IV ketamine is typically reserved for patients with CRPS refractory to standard treatments.

·       - Protocol: Treatment regimens vary. Commonly used protocols include multi-day infusions (e.g., 4–10 days), with or without booster infusions.

·       - Monitoring: Infusions are conducted under close supervision, often in a hospital or ambulatory infusion center. Vital signs, psychological status, and dissociative effects are monitored.

·       - Side Effects: Short-term side effects include nausea, dizziness, dissociation. These are generally reversible and managed with adjunct medications.

Benefits

·       - Substantial pain reduction in a subset of patients

·       - Potential for improved sleep, function, and quality of life

·       - May reduce reliance on opioids and other medications

Limitations

·       - Not all patients respond

·       - Access and insurance coverage may be limited

·       - Functional gains may not parallel pain relief

·       - Long-term safety and optimal dosing protocols continue to be studied

The Future of Ketamine in CRPS

Ketamine represents a growing frontier in pain medicine. New formulations (e.g., intranasal, sublingual) and combination therapies are under investigation.

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1. Schwartzman RJ, Alexander GM, Grothusen JR, Paylor T, Reichenberger E, Perreault M. Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study. Pain. 2009 Dec 15;147(1-3):107-15. doi: 10.1016/j.pain.2009.08.015. Epub 2009 Sep 23. PMID: 19783371.
2. Sigtermans MJ, van Hilten JJ, Bauer MCR, Arbous SM, Marinus J, Sarton EY, Dahan A. Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1. Pain. 2009 Oct;145(3):304-311. doi: 10.1016/j.pain.2009.06.023. Epub 2009 Jul 14. PMID: 19604642.
3. Kirkpatrick AF, Saghafi A, Yang K, Qiu P, Alexander J, Bavry E, Schwartzman R. Optimizing the Treatment of CRPS With Ketamine. Clin J Pain. 2020 Jul;36(7):516-523. doi: 10.1097/AJP.0000000000000831. PMID: 32243301.