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Ketamine as a Treatment Option for Complex Regional Pain Syndrome (CRPS)

Complex Regional Pain Syndrome (CRPS) is a debilitating pain syndrome with the cardinal features including hypersensitivity to pain (hyperalgesia) and the sensation of pain from stimulus that does not normally provoke pain (allodynia). It is estimated that 200,000 people suffer from CRPS annually in the United States, occurring three times more often in women than men.

It is imperative to initiate effective treatment for CRPS soon after diagnosis to prevent progression of symptoms that may otherwise severely affect quality of life. Treatment for CRPS involves a multimodality approach with an array of pharmacological treatment options. IV ketamine has been shown in to be effective at providing pain relief and inducing remission in treatment-resistant patients. IV ketamine is an attractive treatment option for CRPS given is rapid onset, safety profile, limited drug-drug interactions, and non-existent potential for physiological dependence. Additionally, IV ketamine is effective for the treatment of depression and anxiety among other disorders that are often associated in patient suffering from CPRS. Today we will briefly review CRPS and demonstrate how IV ketamine infusion therapy is a great treatment option for those suffering.

What is CRPS?

CRPS is a pain syndrome associated with inflammation that may be results in chronic pain lasting greater than six months. Pain severity may be so severe that it leads to suicidal thoughts and or actions. CRPS is subdivided into two main types:

  1. CRPS Type-I is the most common and does not involve a known nerve injury.
  2. CRPS Type-II is less common and occurs in patients who have suffered from a nerve injury.

A newer third type of CRPS is evolving, known as CRPS with remission of some features. This subdivision included patients with ongoing symptoms of CPRS but symptoms not severe enough to meet full criteria for diagnosis. These patients suffer from CRPS-related pain and features but show some improvement.

Risk Factors and Causes of CRPS

The onset of CRPS is often preceded by trauma or surgery, although it is often difficult to diagnoses which relies on clinical findings rather than specific tests. The underlying pathophysiology of CRPS is unknown, although it is believed to result from nervous system dysfunction. A recent analysis of the patients suffering from CRPS showed that the primary cause included:

  • 42% fractures
  • 21% blunt traumatic injuries excluding fractures
  • 12% surgery
  • 7% carpal tunnel syndrome

The remaining patients in the analysis had less common causes or no clear precipitating event.

CRPS Symptoms

CRPS can occur anywhere in the body but it's common in the arms, hands, legs, and feet. There are several symptoms which include:

  • Pain
  • Burning or stinging
  • Tingling (pins and needles)
  • Discoloration of the skin
  • Swelling
  • Temperature variation of effected area (warm or cold to the touch)
  • Changes in skin, hair, or nails (thinning, shiny appearance, decreased growth)
  • Motor impairment such as weakness and/or muscle spasms

CRPS Treatment Options

Treatment for CRPS include physical therapy, medicines, or involvement of other specialist such a psychiatrist, pain specialist, and occupational therapist. Let’s review some of the options:

  • Physical therapy: Considered first line therapy and essential to keep limb or body part function and mobility
  • Psychotherapy: Depression, anxiety, and suicidal ideation may arise in patient suffering from CRPS, thus talk therapy can help patients cope and recover
  • Medications: There are several options that include Non-Steroidal Anti-Inflammatory Drugs (NSAIDS such as Advil and Ibuprofen), acetaminophen (Tylenol), topical anesthetics, corticosteroids, Botox infections, opioids, and various other medications such as gabapentin, duloxetine, and nortriptyline
  • Spinal cord and other neural stimulation: Electrodes are surgically implanted into the spine and when stimulated may block pain sensations in the spinal cord and brain
  • Spinal fluid drug pumps: Implanted pumps deliver pain-reducing medications or anesthetics into the spinal fluid
  • Surgery: Pain may become so severe that patients require amputations, or other surgical procedures such a nerve blocks or obliteration of nerves (sympathectomy)
  • Holistic and alternative therapies: These include acupuncture, chiropractic, medicinal marijuana & CBD, and other relaxation techniques (progressive muscle relaxation, biofeedback)
  • IV ketamine therapy: Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist which is a novel yet potentially highly effective treatment option

IV Ketamine Infusion Therapy for Treatment of CRPS

The use of ketamine for CRPS can inhibit the sensation of pain by blocking the N-methyl-D-aspartate (NMDA) receptor. The NMDA receptor is found throughout the peripheral and central nervous system (brain and spinal cord), which acts as an ion channel and when stimulated modulates the transmission of pain. Ketamine has also been shown to have anti-inflammatory properties. In addition to its involvement with pain, inflammation may play a role in inducing depressive symptoms associated with major depressive disorder and Treatment-Resistant Depression (TRD).

Metanalysis results of the use of ketamine for the treatment of CRPS has been shown to decrease pain scores with a rate of immediate pain relief being 69%. Pain relief rates at 1-3 month follow-ups were 58%. Further, a retrospective review analyzed 33 patients with CRPS who had undergone ketamine treatment at least once. There was complete pain relief in 76% and partial relief in 18% of patient participants after the initial course of therapy. Notably, all 12 patients who received second courses of treatment experienced complete relief of their CRPS pain.

It's important to note that IV ketamine use for the treatment of pain-related syndromes may require longer infusion times (up to four hours) rather than the standard 40-minute infusion times which are used for mood disorders like depression, anxiety, and PTSD.


Although somewhat rare, CRPS can be severely debilitating and associated with cofounding disorders such as depression and anxiety. IV ketamine has repeatably proven to be a highly effective treatment option for various mental disorders and once again is showing promise for pain syndromes which include CRPS. IV ketamine’s rapid onset and high therapeutic index makes it a promising treatment option for those desiring a safe and non-invasive approach to therapy. At Innerbloom Ketamine Therapy, we offer extended infusions for CRPS and pain disorders. Call us today to see if IV ketamine therapy is right for you.

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