Complex Regional Pain Syndrome (CRPS)

The short version

●CRPS is a chronic pain condition, usually in a limb after an injury or surgery, where the pain is far out of proportion to the original event and comes with changes in skin color, temperature, swelling, sweating, and movement.
●It reflects a malfunction in the peripheral and central nervous and immune systems — including central sensitization — rather than ongoing tissue damage.
●Early, intensive rehabilitation (physical and occupational therapy with graded motor imagery and desensitization) is the cornerstone, alongside neuropathic-pain medications and pain psychology.
●CRPS is one of the chronic-pain conditions with the most supportive ketamine evidence: NMDA-receptor antagonism targets the central sensitization that drives it, and ketamine infusions have shown meaningful pain relief in controlled studies.
●Even so, ketamine is not a cure and the benefit can be temporary; it is used within an aggressive rehabilitation program, not instead of one.
●CRPS is painful and disabling enough to commonly drive depression and anxiety, which ketamine can also address.

Clinical definition

Complex regional pain syndrome is a chronic pain disorder that typically develops in a limb after trauma, surgery, fracture, or immobilization, in which the pain is disproportionately severe and prolonged relative to the inciting event. Diagnosis (the Budapest criteria) requires continuing pain plus signs and symptoms across sensory (hyperalgesia, allodynia), vasomotor (skin color and temperature asymmetry), sudomotor/edema (swelling, sweating changes), and motor/trophic (reduced range of motion, weakness, tremor, changes in hair, nail, and skin) categories, without another diagnosis that better explains them. CRPS type 1 (formerly reflex sympathetic dystrophy) occurs without a confirmed nerve injury; type 2 (formerly causalgia) follows an identifiable nerve injury. The underlying mechanisms involve peripheral and central sensitization, aberrant inflammatory and immune signaling, and altered cortical representation of the affected limb — which is why it behaves so differently from ordinary post-injury pain.

How it differs from related conditions

vs. Chronic pain

CRPS is a specific, criteria-defined regional syndrome with characteristic autonomic and trophic signs; chronic pain is the broad category. CRPS is one of its more distinctive and ketamine-responsive forms.

vs. Neuropathic pain

CRPS involves neuropathic features but adds the vasomotor, sudomotor, edema, and motor/trophic changes that define it; type 2 CRPS specifically follows nerve injury.

vs. Peripheral neuropathy

Generalized nerve damage (e.g., diabetic) causes symmetric, distribution-following symptoms; CRPS is regional, disproportionate, and accompanied by autonomic limb changes.

vs. Depression

The severity and disability of CRPS frequently drive depression and anxiety; mood should be screened and treated as part of comprehensive care.

First-line treatments

Intensive physical and occupational therapy

The cornerstone — graded motor imagery, mirror therapy, desensitization, and functional restoration. Early, active movement of the limb prevents the disuse that worsens CRPS.

Neuropathic-pain medications

Gabapentinoids, tricyclics or SNRIs, and topical agents; bisphosphonates and short steroid courses have evidence in selected early cases.

Pain psychology

CBT and graded exposure address the fear-avoidance and disability cycle and the high emotional burden of CRPS.

Interventional options

Sympathetic blocks, spinal cord stimulation, and other procedures in refractory cases, matched to the clinical picture and trajectory.

When standard treatments fail

CRPS is notoriously difficult, and refractory cases are common. The approach is to keep functional rehabilitation central (loss of the limb to disuse is the worst outcome), combine neuropathic agents, treat the substantial depression and anxiety that accompany the condition, and escalate to interventional options such as sympathetic blocks or spinal cord stimulation. Because central sensitization is core to CRPS, glutamatergic NMDA-antagonist treatment with ketamine has more supporting evidence here than in most pain conditions and is a recognized option for the refractory subgroup, delivered alongside — never instead of — aggressive rehabilitation.

Where ketamine fits

CRPS is one of the chronic-pain conditions where ketamine has the clearest rationale and some of the better controlled evidence. As a potent NMDA-receptor antagonist, ketamine targets the central sensitization that drives CRPS, and controlled studies of ketamine in CRPS have shown meaningful reductions in pain, with associated improvements in function in some patients (Schilder 2013); multi-society pain guidelines include CRPS among the conditions for which intravenous ketamine is supported (Cohen 2018). Important caveats: the benefit is often partial and can be temporary, ketamine does not reverse the underlying disorder, and it works only as part of an intensive rehabilitation program — the functional restoration of the limb remains the goal. Ketamine also addresses the depression and anxiety that frequently accompany the severe disability of CRPS. It is considered for refractory CRPS within comprehensive specialist care.

Where this fits with Tovani

CRPS is a complex condition usually co-managed with a pain specialist and rehabilitation team. Tovani's role is most appropriate when CRPS coexists with treatment-resistant depression or when a patient's specialist team has identified ketamine as part of the plan; eligibility screening captures the diagnosis, current rehabilitation, and mood. Tovani emphasizes that ketamine supports — and never replaces — the functional rehabilitation that determines long-term outcome, and coordinates with the patient's existing pain care rather than working in isolation.

Check eligibility How Tovani treats Complex Regional Pain Syndrome Find treatment options The science behind ketamine

Frequently asked

Is ketamine a recognized treatment for CRPS?

CRPS is one of the chronic-pain conditions with the most supportive ketamine evidence — controlled studies have shown meaningful pain relief, and pain-society guidelines include it among supported indications. That said, the benefit is often partial and can be temporary, and ketamine works as part of an intensive rehabilitation program, not on its own.

Will ketamine cure my CRPS?

No. Ketamine can reduce CRPS pain and, for some, improve function, but it does not reverse the underlying disorder. The goal of treatment is functional restoration of the limb through rehabilitation; ketamine is a tool to make that work possible, not a cure.

Why is movement so important if it hurts?

Loss of the limb to disuse is the worst CRPS outcome, and the condition involves altered brain representation of the limb that active, graded movement (including mirror therapy and graded motor imagery) helps retrain. Pain relief from any source, including ketamine, is most valuable when it enables that rehabilitation.

CRPS has made me depressed — can ketamine help that too?

Yes. The severe pain and disability of CRPS frequently cause depression and anxiety, and ketamine has strong evidence for treatment-resistant depression. Addressing mood is part of comprehensive CRPS care, and Tovani screens for it.

References

Schilder JC et al. 2013, The Journal of Pain — Study of ketamine in CRPS finding that pain relief was associated with improvement in motor function. (PMID 24075073)
Cohen SP et al. 2018, Regional Anesthesia and Pain Medicine — Multi-society consensus guidelines including CRPS among chronic pain conditions supported for intravenous ketamine. (PMID 29870458)
Sanacora G et al. 2017, JAMA Psychiatry — APA consensus on ketamine's use and safety, relevant to the depression that commonly accompanies CRPS. (PMID 28249076)

Last reviewed by Dr. Ben Soffer, DO on May 31, 2026. This page is educational and not a substitute for clinical evaluation. A physician determines whether ketamine therapy is appropriate for your specific situation.