Ketamine for CRPS: A Case of Long-Term Pain Relief

Complex regional pain syndrome is one of the most severe chronic pain conditions in medicine. Characterized by intense burning pain, swelling, and changes in skin color and temperature — typically in a limb — CRPS can be profoundly disabling. When it occurs alongside limb dystonia, involuntary sustained muscle contractions that twist the affected limb into abnormal postures, the suffering is compounded. Treatment options for CRPS-associated dystonia are limited, and many patients cycle through medications, nerve blocks, and physical therapy with inadequate relief. A 2026 case report by AlZahrani and colleagues, published in BMJ Case Reports, documents a striking outcome: long-term resolution of both CRPS pain and associated limb dystonia following ketamine infusion therapy.

Understanding CRPS and dystonia

CRPS typically develops after an injury, surgery, or even a minor trauma such as a sprain. The pain is disproportionate to the original injury and persists long after tissues have healed. The underlying mechanism involves a combination of peripheral nerve sensitization, central sensitization in the spinal cord and brain, neuroinflammation, and autonomic nervous system dysfunction. In effect, the nervous system becomes stuck in a state of alarm, amplifying pain signals and generating symptoms that extend far beyond the original injury site.

Dystonia in CRPS — involuntary muscle contractions causing abnormal limb postures — is a particularly challenging complication. It occurs in a subset of CRPS patients and is thought to involve dysfunction in the basal ganglia and other motor circuits, possibly driven by the same central sensitization processes that sustain the pain. Conventional treatments for CRPS-associated dystonia include baclofen, benzodiazepines, botulinum toxin injections, and physical rehabilitation, but response rates are inconsistent and many patients remain significantly impaired.

The case

In the AlZahrani et al. report, the patient received ketamine infusions and achieved long-term relief of both the chronic pain and the dystonia. This outcome is notable for several reasons. First, dystonia associated with CRPS is notoriously difficult to treat. Second, the relief was sustained — not merely a transient effect during or immediately after the infusion. Third, the case demonstrates that ketamine's therapeutic effects can extend beyond pain reduction to include resolution of motor symptoms that are mechanistically linked to central sensitization.

The authors contextualize this case within the broader evidence base. Meta-analytic data on ketamine for CRPS indicate that the average immediate pain reduction following ketamine infusion is clinically significant, though the duration of benefit varies across studies. What makes the AlZahrani case distinctive is the sustained improvement in the dystonic component, which has been less systematically studied.

How ketamine works in CRPS

Ketamine's relevance to CRPS stems from its action on the NMDA receptor. In CRPS, NMDA receptors in the spinal cord and brain become hyperactivated as part of the central sensitization process. This hyperactivation amplifies pain signals and contributes to the maintenance of abnormal neural patterns, including those that may drive dystonia. By blocking NMDA receptors, ketamine can interrupt this pathological cycle, effectively "resetting" sensitized neural circuits.

Beyond NMDA antagonism, ketamine has anti-inflammatory properties — it reduces levels of pro-inflammatory cytokines and modulates microglial activation in the central nervous system. Since neuroinflammation is a key driver of CRPS, this anti-inflammatory action may contribute to the sustained benefit observed in the case report. Ketamine also promotes neuroplasticity through increased BDNF (brain-derived neurotrophic factor) release, which may help the nervous system establish healthier signaling patterns after the acute effects of the drug have worn off.

From IV infusions to oral ketamine

The AlZahrani case involved intravenous ketamine, which allows precise dose titration and is the most commonly studied route for CRPS. However, the fundamental mechanisms through which ketamine acts — NMDA receptor antagonism, anti-inflammatory effects, neuroplasticity promotion — are not exclusive to the IV route. Oral and sublingual ketamine formulations also achieve systemic absorption and central nervous system penetration, albeit with different pharmacokinetic profiles.

For patients with chronic pain conditions who also experience comorbid depression or anxiety, oral ketamine therapy offers a practical option that does not require repeated visits to an infusion center. The neuroplastic and anti-inflammatory mechanisms that appear to benefit CRPS patients overlap substantially with the mechanisms responsible for ketamine's antidepressant effects. This dual action is especially relevant given the high rates of depression and anxiety among chronic pain patients.

The Isha Health perspective

At Isha Health, our primary treatment focus is on depression, anxiety, and PTSD through physician-supervised at-home ketamine therapy. However, we recognize that chronic pain and mood disorders are deeply interconnected. Many of our patients live with both conditions, and the neurobiological overlap between pain and depression means that ketamine therapy initiated for mood improvement may also influence pain processing.

The AlZahrani case report adds to a growing body of evidence — including the 2026 systematic review of ketamine for chronic non-cancer pain and research on ketamine for comorbid chronic pain and depression — suggesting that ketamine's benefits extend across the pain-mood spectrum. For patients with chronic pain, these findings are worth discussing with a qualified physician.

The bottom line

A single case report does not establish a standard of care, and CRPS is a complex condition that requires multidisciplinary management. But the AlZahrani et al. case is clinically meaningful because it demonstrates that ketamine can produce sustained relief of both pain and dystonia in CRPS — two symptoms that share underlying mechanisms of central sensitization and neuroinflammation. As the evidence base grows, ketamine's role in treating refractory pain conditions will become clearer.

Reference: AlZahrani T, et al. "Long-term relief of CRPS-associated limb dystonia with ketamine infusion: a case report." BMJ Case Reports. 2026.

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