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Ketamine Resets System for Normal Pain Processing in Complex Syndrome Patients

by U.S. Medicine

October 11, 2012

By Annette M. Boyle

BETHESDA, MD — For patients with intractable complex regional pain syndrome (CRPS), treatment with high doses of ketamine may offer a cure or dramatically reduce pain and improve functioning. Better still, this innovative treatment soon might be available on an outpatient basis.

Researchers at Walter Reed National Military Medical Center (WRNMMC), Bethesda, MD, already have treated two patients with severe CRPS as outpatients.


Navy Cdr. James S. Houston, MD, Director, Wounded Warrior Pain Care Initiative, and Director, Interventional Pain Clinic, WRNMMC

“Patients who have not responded to conventional treatments for CRPS or phantom-limb pain, such as medications, nerve blocks and spinal-cord stimulation, can find good relief with an outpatient infusion of ketamine,” said Navy Cdr. James S. Houston MD, director, Wounded Warrior Pain Care Initiative, and director, Interventional Pain Clinic, WRNMMC. “We have treated two patients here, and both are doing extremely well.” Outpatient treatment of CRPS with ketamine infusion currently is available only at WRNMMC.

Patients receive a subanesthetic dose of ketamine, about 120 mg per hour for an average adult male, for four or five hours. After the infusion is finished, patients wait two hours, or until any side effects have resolved, then go home. “Compared to inpatient infusion, this treatment is far more cost-effective and much more convenient for patients,” Houston told US Medicine.

“Patients experience significant relief for one to two months, with either a 50% reduction in overall pain or a 50% reduction in the area of pain. One patient had CRPS that involved the entire leg, from foot to hip. After treatment, the pain was pushed down to just the ankle. That level of pain reduction enables patients to be more functional, return to work, go shopping, rather than be bedridden,” Houston explained.

A previous study at Mackay Base Hospital in Queensland, Australia, reported that, of 33 patients with CRPS who received subanesthetic infusions of ketamine, 25 (76%) obtained complete pain relief, while six (18%) had partial pain relief after one course of therapy. More than half remained pain-free for more three months or longer, and 31% had no pain for at least six months.

Twelve patients relapsed and had a second course. All 12 experienced complete pain relief; 58% were pain-free for more than year after treatment, and one-third had no pain for more than three years.

“Ketamine works extremely well for neuropathic pain, phantom-limb pain and CRPS — conditions for which opioids and other medications work poorly,” Houston said.

Hyper-regulation and central sensitization triggered by stimulation of the N-methyl-D-Aspartate (NMDA) receptors appear to be the primary neurological processes involved in CRPS and neuropathic pain, according to the guidelines for very high dose ketamine infusions developed at Walter Reed. Ketamine blocks the NMDA receptors.

“At higher doses, ketamine changes central pain-processing. In lay language, it’s like hitting the ‘reset’ button or control/alt/delete on your computer. It restores normal pain processing,” said Houston. “For patients who have opioid-induced hyperalgia or neuropathic pain, ketamine can provide immediate and dramatic relief.”

Ketamine ‘Resets’ System for Normal Pain Processing in Complex Syndrome Patients

Ketamine-Induced Coma

Initial research on ketamine for CRPS focused on the inpatient setting.

Symptoms of CRPS
The key symptom of CRPS is continuous, intense pain out of proportion to the severity of the injury (if an injury has occurred), which gets worse rather than better over time. CRPS most often affects one of the extremities (arms, legs, hands, or feet) and is also often accompanied by:

  • “burning” pain
  • increased skin sensitivity
  • changes in skin temperature: warmer or cooler compared to the opposite extremity
  • changes in skin color: often blotchy, purple, pale, or red
  • changes in skin texture: shiny and thin, and sometimes excessively sweaty
  • changes in nail and hair growth patterns
  • swelling and stiffness in affected joints
  • motor disability, with decreased ability to move the affected body part

Often the pain spreads to include the entire arm or leg, even though the initiating injury might have been only to a finger or toe. Pain can sometimes even travel to the opposite extremity. It may be heightened by emotional stress.

“While we don’t really know all the reasons patients develop CRPS, data from Europe and Mexico show that using very high doses of ketamine in an intensive care (ICU) or post-anesthesia care unit (PACU) setting produces a dramatic reduction in CRPS,” noted Houston. “With a ‘ketamine coma,’ one-third of patients have full resolution of symptoms: They are cured. One-third experience dramatic, permanent reduction in pain. Others have temporary relief. There is a much higher response rate than with other treatment modalities.”

Hospitalized patients who are intubated and ventilated receive an average of 500 mg of ketamine per hour for five days. Prior research showed that three days was insufficient and that no additional benefit was seen after five days. Patients typically leave the hospital two days after terminating the infusion.

To monitor the neurocognitive effects of ketamine, patients undergo psychological assessments prior to treatment, immediately following treatment and six weeks later.

“Immediately following treatment, we note some vision changes, some hallucinations. But at the six-week mark, patients are actually better and more functional than at baseline. With the severe, chronic pain resolved, they can focus, function and respond better,” Houston said.

“We’ve had about two-dozen patients in ketamine comas in the ICU to treat pain. Some of them had neuropathic pain, and, when they went in for surgery, we used ketamine for sedation and kept them intubated,” he added.

Not everyone with CRPS, phantom-limb pain or other neuropathic pain is a candidate for ketamine treatment. Inducing a coma and ventilating a patient for five days is a high-risk procedure, Houston explained, and patients must have tried injections, nerve blocks, spinal-cord stimulation and other conventional treatments first. Typical candidates have disabling pain that has made them nonfunctional or created severe psychological distress.

“CRPS can make people suicidal. We want to help them before they get to the point of considering suicide or amputation for a limb involved in CRPS. Some patients think that removing a limb will eliminate the pain, but CPRS is a disorder of nerve processing, not of the limb, so amputation is ineffective. We want to provide a treatment that will work,” said Houston.

Proactive Use of Ketamine

The best approach to chronic pain is prevention, and ketamine may be able to help there, too. “We are using the treatment now for patients coming in from Afghanistan with multiple injuries. Using ketamine for sedation, we could prevent potential phantom-limb pain. There isn’t a lot of data yet, but it seems that using a higher dose of ketamine closer to the time of trauma may prevent some cases of neuropathic pain and phantom limb pain,” Houston recounted.

For now, the team at Walter Reed is focused on presenting the results of the international research and their own experience, as well as the protocol they’ve developed for use of ketamine in patients in military hospitals.

“Our goal is to identify more patients and get the information about this therapy out so more patients can find relief,” Houston said.

Back to October Articles

[1] Correll GE, Maleki J, Gracely EJ, Muir JJ, Harbut RE. Subanesthetic ketamine infusion therapy: A Retrospective Analysis of a Novel Therapeutic Approach to Complex Regional Pain Syndrome. Pain Medicine. 2004;3:263-275. http://www.thblack.com/links/RSD/PainMed2004_5_263_ketamine_infusion_therapy.pdf


16 Comments

  • James Mullarky says:

    You should also consider administering Cycloserine during the post treatment periods to extend the effect of the pain relief. This antibiotic in combination with other meds has had tremendous benefits for someone I love. The small molecule penetrates the blood brain barrier and helps quiet the part of the brain that remembers pain – not many side effects.

    It’s good to hear that med professionals are trying new things to help those suffering chronic nerve or phantom pain. Chronic memory or nerve pain is so misunderstood by most medical professionals. I’m now hoping to convince my loved one to try this infusion therapy.

  • john b says:

    I had crps/rsd for almost 7 years post op on a knee replacement, and also had drop foot along with it….went thru all the meds and the nightmares, implant stimulator etc…and was truly close to throwing in the towel when ifound a doc in Albuquerque who did the ketamine IV process….spent 5 or 6 days in intensive care and came out with NO PAIN…and no longer taking the heavy pain meds I had 5 days earlier….this can be such a painful, terrible condition….I truly have a new life, and feel very, very very lucky…..best regards….jb in new mexico.

  • Kate says:

    Hi John B, was the pain you had post knee surgery only from your foot drop or from something else as well? I have foot drop and am taking daily morphine but it doesn’t take care of all the pain, tingling, buzzing numbness, etc., it’s awful and I can’t sleep, concentrate, etc. Can you share the exact location you had treatment at, how high the dosages were? Thanks and SO happy you’re not I pain anymore!

  • Kate says:

    Hi John B, was the pain you had post knee surgery only from your foot drop or from something else as well? I have foot drop and am taking daily morphine but it doesn’t take care of all the pain, tingling, buzzing numbness, etc., it’s awful and I can’t sleep, concentrate, etc. Can you share the exact location you had treatment at, how high the dosages were? Thanks and SO happy you’re not I pain anymore!

  • Monica says:

    Do you know if ketamine blocks work for long term RSD? I have had RSD for 14 years. It is in all of my limbs. I am able to walk very short distances and I do work full time. Interested in other long term pain sufferers and how ketamine works.

  • Donna R says:

    I have full body crps/RSD for four years. I’ve had many OP treatments of IV Ketamine but it’s never worked for me. I have a reputable pm doctor. Treatmental protocol was based on Dr. Shwartsman (sp?) of 35 years ago. Any suggestions or ideas? I do not want intensive care or coma treatment. I know that some people do not respond to ketamine. I get 300 ml over 4 hrs. Any opinions?

  • KEVIN C MORSE JR says:

    I have below knee Amputation, after 3 major falls last Oct 2016 I began to get CRPS. My leg gets white and cold at the end, it feels like my leg is hotdog over cooked and split. I have full body sweats. Extreme pain. I have been going thru W Roxbury and Jamaica Plains VA to no prevail. I need help. Getting worse.

  • KEVIN C MORSE JR says:

    I have below knee Amputation, after 3 major falls last Oct 2016 I began to get CRPS. My leg gets white and cold at the end, it feels like my leg is hotdog over cooked and split. I have full body sweats. Extreme pain. I have been going thru W Roxbury and Jamaica Plains VA to no prevail. I need help. Getting worse.

  • Jane says:

    the current VA Sec Dr David Shulkin does endorse ketamine infusions for CRPS email/call him the VA Chief of Staff Deputy Chief of Staff and the current Under Secretary of Health veterans if not at the VA are getting care at Stanford Hospital, University of New Mexico, University of Virginia, Florida Spine Institute Walter Reed NMMC, as well all paid for by the VA!your VA is ling to sadly and being lazy IMO

  • Hannah says:

    I’ve had rsd/CRPS for 3 years;pain meds,blocks,and a spinal cord implant did not work. After 2 4 hour ketamine infusions I feel 50perscent better. Try it!

  • Hannah says:

    I’ve had rsd/CRPS for 3 years;pain meds,blocks,and a spinal cord implant did not work. After 2 4 hour ketamine infusions I feel 50perscent better. Try it!

  • john b says:

    I had crps/rsd for almost 7 years post op on a knee replacement, and also had drop foot along with it….went thru all the meds and the nightmares, implant stimulator etc…and was truly close to throwing in the towel when ifound a doc in Albuquerque who did the ketamine IV process….spent 5 or 6 days in intensive care and came out with NO PAIN…and no longer taking the heavy pain meds I had 5 days earlier….this can be such a painful, terrible condition….I truly have a new life, and feel very, very very lucky…..best regards….jb in new mexico.

  • James Mullarky says:

    You should also consider administering Cycloserine during the post treatment periods to extend the effect of the pain relief. This antibiotic in combination with other meds has had tremendous benefits for someone I love. The small molecule penetrates the blood brain barrier and helps quiet the part of the brain that remembers pain – not many side effects.

    It’s good to hear that med professionals are trying new things to help those suffering chronic nerve or phantom pain. Chronic memory or nerve pain is so misunderstood by most medical professionals. I’m now hoping to convince my loved one to try this infusion therapy.

  • Monica says:

    Do you know if ketamine blocks work for long term RSD? I have had RSD for 14 years. It is in all of my limbs. I am able to walk very short distances and I do work full time. Interested in other long term pain sufferers and how ketamine works.

  • Donna R says:

    I have full body crps/RSD for four years. I’ve had many OP treatments of IV Ketamine but it’s never worked for me. I have a reputable pm doctor. Treatmental protocol was based on Dr. Shwartsman (sp?) of 35 years ago. Any suggestions or ideas? I do not want intensive care or coma treatment. I know that some people do not respond to ketamine. I get 300 ml over 4 hrs. Any opinions?

  • Jane says:

    the current VA Sec Dr David Shulkin does endorse ketamine infusions for CRPS email/call him the VA Chief of Staff Deputy Chief of Staff and the current Under Secretary of Health veterans if not at the VA are getting care at Stanford Hospital, University of New Mexico, University of Virginia, Florida Spine Institute Walter Reed NMMC, as well all paid for by the VA!your VA is ling to sadly and being lazy IMO


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