Can symptoms of CRPS be remitted using low-dose Naltrexone?

Following recent articles on treatment and clinical trials involving Neridronate and Zoledronaterespectively, we have heard that Stanford University are currently recruiting participants for a clinical trial of low-dose Naltrexone in the treatment of CRPS.


Traditionally it was thought that pain signals were transmitted through and affected solely by neurons. However, some years ago it was discovered that non-neuronal cells in the spinal cord called neuroglia or glia, actually amplify pain when they receive certain signals from the peripheral nervous system.

In CRPS there is both central sensitisation of the central nervous system and activation of the glia. The drug Naltrexone acts to reduce the affect of the glia in amplifying pain.


In higher doses, Naltrexone is used largely in the treatment of alcohol and opioid dependency. In low doses, however, it has been heralded in some quarters as a “wonder drug” in the treatment of conditions as diverse as cancer, multiple sclerosis, fibromyalgia and Parkinson’s Disease. But can it benefit those suffering CRPS?

Reported cases

In 2013, the Journal of Neuroimmune Pharmacology reported the cases of two people with seemingly therapy-resistant CRPS, who were prescribed low dose Naltrexone (LDN) in addition to their regular medication.

Case 1

This case involved a 48 year old man who developed symptoms of CRPS following an injury to his right leg. Within 3 years the CRPS had spread to his upper limbs, where he also developed dystonia. He received a variety of treatment and medication including anticonvulsants, antidepressants, opioids, physical therapy and psychotherapy. Infusions of Ketamine proved initially beneficial but this was not sustained with repeat infusions.

However, it was reported that within 4 weeks of commencing low dose Naltrexone:

the patient’s requirements for the lower dose intravenous ketamine infusions were not as frequent…The patient recovered from CRPS flares more quickly, felt more energetic, and tolerated pain better. He became physically more active, and his sleep improved significantly. Within 2 months after starting LDN, the patient’s dystonic spasms discontinued, although he still had moderate pain in both upper extremities. The patient was able to walk without a cane, which he had used continuously [for 6 years]. His pain was an average of 8 to 10 on the Numeric Rating Scale (NRS) before starting LDN. It dropped down to an average of 5 to 6 on the NRS after starting LDN. After LDN therapy, the patient’s pain symptoms have reduced in severity, but not in their distribution. His current mood state is good. No side effects of LDN were noted.

Case 2

This case involved a young girl who suffered from a genetic disorder which resulted in multiple dislocations of her right shoulder and right ankle, as well as a number of other medical conditions. When she was about 7 years old she first developed symptoms of CRPS in her lower right leg which spread and she also developed dystonia in her upper limbs and fixed dystonia in her lower right leg and ankle.

After commencing low dose Naltrexone, it was reported:

Remarkably, the patient did not experience any [further] spread of her CRPS, despite undergoing multiple invasive procedures, including surgery…The patient still has a chronic shoulder dislocation, associated with her [underlying genetic condition]. However, her CRPS symptoms have resolved completely. The patient has been maintained on LDN for 18 months. No side effects of LDN have been noted.


The authors of the study concluded:

The remission of pain and dystonic spasms in Case 1, as well a remission of all CRPS symptoms (including fixed dystonia) in Case 2, provide evidence that a multi-modal interventional approach, which includes low-dose naltrexone…should be considered as a treatment option for the treatment of CRPS patients, particularly those patients with dystonic movement disorders.

With such promising results in these two reported cases it is encouraging to see that a formal clinical trial is now planned.

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