By Pat Anson, PNN Editor

Chronic Regional Pain Syndrome (CRPS) is one of the worst and most baffling of pain conditions. It usually starts after an injury to an arm or leg, with the skin in the affected area becoming warm, red and painful to touch. Most cases are mild and people recover after a few months, but in rare cases the condition grows worse, resulting in intense nerve pain that can spread and last for years.

Why do some people develop CRPS, while others get better? A small new study in the UK suggests that a genetic variant may be responsible for about a third of CRPS cases.

Researchers at the University of Cambridge took blood samples from 84 patients enrolled in the CRPS-UK Registry to look for variations in certain genes known as single nucleotide polymorphisms, or SNPs for short. Their DNA was compared to a control group of patients with chronic pain from fibromyalgia and low back pain.

Their findings, recently published in the Journal of Medical Genetics, show that an SNP in 4 genes (ANO10, P2RX7, PRKAG1 and SLC12A9) was “more common than expected” in patients with CRPS for at least a year (CRPS-1) than it was in the fibromyalgia/back pain group.

In all, 25 of the 84 patients (30%) with CRPS-1 had the variations in at least 1 of the 4 genes. None of the variations was found in the control group.

Interestingly, men with CRPS were more likely to have the variations (57%) than women (24%), although the sample sizes are so small the discrepancy will need to be confirmed in a larger study. In real life, women are more likely to have CRPS than men.

“This raises the possibility of different mechanisms of disease in males and females in CRPS-1 and that therapeutic responses may also be influenced by sex,” wrote lead author C. Geoffrey Woods, a clinical geneticist at the Cambridge Institute for Medical Research.  “Our data support an underlying genetic predisposition to CRPS-1 in up to a third of cases, with this effect being most prominent in males.”

There may be a biological explanation for the findings, because the ANO10, P2RX7and SLC12A9 genes are found in immune cells of the peripheral nervous system, which becomes inflamed by CRPS.

All 4 genes are also expressed in macrophages — a type of white blood cell involved in the immune response of healthy people. This suggests that variations in those 4 genes may be what triggers CRPS, which is also known as Reflex Sympathetic Dystrophy (RSD).

CRPS/RSD is difficult to treat and there is no known cure. Some patients have found relief through Scrambler therapy and ketamine infusions.