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Complex Regional Pain Syndrome (CRPS) is a condition involving chronic, severe pain of a an arm or leg, usually occurring after an injury to that limb. The symptoms can involve the area of the injury, but can also spread to the entire limb and even the opposite side. The pain is described as tightness, burning and pins and needles and can also include increased sensitivity of the skin with changes in skin temperature, skin color and/or swelling.

The symptoms result from damage to the nerves controlling blood flow and temperature. CRPS occurs more often in women and in people around 40 years old, but can develop at any age.

The diagnosis is based on the person’s medical history and signs and symptoms. There is no definitive test for CRPS. It is important, however, to rule out other conditions that have similar symptoms but require different treatment.

Treatment may include physical therapy, non-steroidal anti-inflammatories, steroids, antiseizure drugs that help with neuropathic pain, topical anesthetic creams, nerve block and neural stimulation. Some newer treatments include intravenous immune globulin and intravenous ketamine. Some people find that acupuncture, behavior modification, biofeedback and relaxation techniques also help.

Research with Low-dose Naltrexone (LDN) in CRPS

There have been no clinical trials using LDN in CRPS, but there have been published case reports and a retrospective chart review.

In one report published in the International Journal of Pharmaceutical Compounding in 2016, in a patient with CRPS Type I refractory to other treatments, LDN “dramatically improved the patient’s pain symptoms”.

Two other case reports were described in the Journal of Neuroimmune Pharmacology in 2013.

The first is of a 48 year old male who developed CRPS with severe skin changes. He was treated with opioids, pregabalin and duloxetine. His pain became so severe he could no longer walk without assistance. After heart surgery for another problem, his CRPS progressed and involved his upper chest, upper arms and forearms. He was treated with anticonvulsants, antidepressants, physical therapy, psychotherapy, topical and systemic pain medications including opioids and other intravenous medications. At the time he was started on low-dose naltrexone 4.5 mg daily, narcotics were discontinued, but he was kept on tramadol. At that time he had increased skin sensitivity to pain, numbness and tingling, color and temperature changes and swelling.

After two months of LDN, “he recovered from his flares more quickly, felt more energetic, and tolerated pain better. He became physically more active and his sleep improved significantly. His spasms stopped and he was able to walk without a cane”. His pain went from an 8 to 10 out of 10 to an average of 5 to 6. He had no side effects from LDN.

The second case report is of a 12 year old girl with the genetic disorder, Ehlers-Danlos Syndrome. She had repeated dislocations of her right shoulder and ankle and subsequently developed CRPS. Her symptoms included skin color change, increased temperature, increased sensitivity to pain, numbness and tingling. She was on multiple medications yet her pain was described as an 8 to 10 out of 10.

She was started on LDN 3 mg daily, which was increased to 4.5 mg daily after one month. Her pain scores dropped to 3 to 5 out of 10. She had less sensitivity to pain, touch and temperature change. Eventually she needed surgery for the dislocated ankle and reported a decrease in her post-operative pain from LDN. At the time of publication of the report, she had been on LDN for 18 months with no side effects.

In April 2016, a retrospective chart review was done and published in the Journal of Pain. Twenty-seven patients with chronic pain, including some with CRPS, were treated with LDN 4.5 mg daily. They were asked to complete symptom surveys between 31 to 60 days after starting treatment and then again between 61 and 90 days. Patients taking LDN reported “significantly lower average pain scores, lower “lowest” pain scores, and improved physical function”. Depression scores were also significantly reduced and physical function improved. LDN was well tolerated.

Read the studies about the use of LDN in CRPS here.

Learn more about LDN’s mechanism of action here.