Ketamine Resets System for Normal Pain Processing in Complex Syndrome Patients

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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.”

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