Complex Regional Pain Syndrome (CRPS), sometimes also called Reflex Sympathetic Dystrophy (RSD), is a neuro-inflammatory disorder characterized by chronic, intense pain. It is often caused by damage to nerves from an injury but there are cases where the cause is not known. The condition likely develops after an injury due to a dysfunction in the nervous systems, although there may be many factors that contribute to its development. The most common cause of CRPS is limb trauma that requires a cast and immobilization for a period of time while the limb heals. While treatment of CRPS involves multiple methods including physical rehabilitation and psychological support, medications are an essential part of managing this difficult condition.

Symptoms of CRPS

CRPS results in chronic regional pain that is out of proportion to the pain of the initial injury. In many cases the pain will spread from the area of injury. The pain can be intense and is often associated with a burning sensation. There may also be swelling and stiffness in joints and changes in how the skin responds to temperature. Blotchiness, redness, and thinning of the skin can also occur. Since there is no cure for CRPS, treatment involves finding methods to manage pain and relieve other symptoms. The RSD Society of America has a comprehensive list of symptoms on its website, which can be viewed here: https://rsds.org/.

Pharmacological Treatments for Complex Regional Pain Syndrome

The drugs that are used to treat CRPS include different kind of pain relievers and anesthetics. Some of the drugs used for managing CRPS symptoms include:

• NSAIDs – Both oral and topical NSAIDs are used to treat pain and inflammation. They include ketoprofen, indomethacin, ibuprofen, and more.
• Gabapentin – Seizure medications like gabapentin that treat neuropathic pain can be effective because the pain from CRPS is associated with nerve damage. Gabapentin treats pain that results from overactive pain pathways.
• Ketamine – The NMDA receptor antagonist ketamine has not frequently been used for CRPS because the effective dosage tends to have a high level of toxicity. New research shows that ketamine is a promising pain treatment when applied topically either in a cream or nasal spray. Topical administration may minimize systemic effects by keeping blood levels of the drug lower than when taken orally.
• Lidocaine – Anesthetics like lidocaine can be applied topically in a cream to numb the area of pain. Other anesthetics used topically include benzocaine and tetracaine.

Topical Pain Gels and Creams

Managing the symptoms of complex regional pain syndrome often involves the use of multiple types of pain relief. Many of the treatments that are effective orally can also be made into a topical cream or gel by a compounding pharmacy. NSAIDs like ketoprofen can be compounded into pain rubs along with drugs for treating neuropathic pain like gabapentin.  In addition to these medicated ingredients, pain gels also can contain counterirritants that help distract the body from pain. These ingredients can all be made into one gel or cream by a compounding pharmacy.

Topical Ketamine

While ketamine only has FDA-approved indications for intravenous and intramuscular use, topical administration has been used by healthcare practitioners for many years. Topically applied ketamine in the form of a nasal spray or cream has been studied recently as a possible treatment for complex regional pain syndrome. Topical ketamine may be an effective treatment option for CRPS with a low incidence of side effects. While it has been studied most frequently for use by emergency departments, some healthcare providers are now prescribing it for chronic neuropathic pain.

• When a ketamine gel was used in five patients with neuropathic pain it resulted in pain relief along with an improved sense of temperature and decreased tension in the area of application. No significant side effects were reported in this case study. (Study: Topical ketamine gel: possible role in treating neuropathic pain)
• Intranasal ketamine has also been studied for use in emergency rooms as an effective way to manage pain while minimizing effects on the respiratory system and on heart rate. This study included 34 participants and the majority of patients experienced significant improvement after 15 minutes and saw greater improvement 30 minutes after application. (Study: Intranasal ketamine for the treatment of patients with acute pain in the emergency department).
• In another emergency department study, 88% of participants who were given intranasal ketamine had a clinically significant decrease in VAS scores. (Study: Intranasal ketamine for analgesia in the emergency department: a prospective observational series.).

Low Dose Naltrexone

LDN is a lower dose of the FDA-approved drug naltrexone, which has been used for many years to treat opioid addiction. There are several theories as to why LDN is effective for a variety of conditions but it is likely due to its ability to increase production of endorphins. Some patients have found success taking LDN for complex regional pain syndrome with decreased pain and improvements in dystonia.