July 12, 2024

Genetic Predisposition Accounts for One-Third of Chronic Regional Pain Syndrome Cases

A recent study suggests that genetic factors may contribute to approximately one-third of cases of chronic regional pain syndrome (CRPS). However, interestingly, the condition is less common in men, despite them having a higher likelihood of carrying four genetic variations associated with an increased risk. This finding implies that there may be sex-specific causes at play, according to the researchers.

CRPS is typically triggered by an injury, which leads to hypersensitivity in the affected body part, causing severe pain even with minimal touch or temperature changes. Although the condition often improves over time, some individuals endure intense pain for many years, making it challenging to manage effectively.

The reasons why some people develop CRPS after an injury while others do not remain unclear. However, some researchers have suggested a hereditary component in the onset of CRPS, which has prompted the theory that certain individuals may have a genetic predisposition to the condition.
To investigate further, the researchers examined DNA samples from 34 individuals diagnosed with CRPS (discovery group) for variations in genes known as single nucleotide polymorphisms (SNPs). These variations were then compared to 39 individuals with chronic back pain (comparison group) and an additional 50 individuals with CRPS (confirmatory group). The participants’ age ranged from 20 to 86 years, with an average age of mid-40s to mid-50s across all three groups.

The study revealed that a single SNP in each of four genes (ANO10, P2RX7, PRKAG1, and SLC12A9) was more prevalent in individuals with CRPS in both the discovery and confirmatory groups compared to the back pain group. Out of the 84 patients who had been diagnosed with CRPS for over a year, 25 (30%) exhibited variations in at least one of the four genes. Notably, none of these genetic variations were found in individuals with chronic back pain.

Although CRPS is more common in men than women at a ratio of 3-4:1, interestingly, more men than women expressed these genetic variations (57% vs. 24%). However, the researchers note that a larger study group is necessary to confirm this discrepancy and explore potential sex-related mechanisms and therapeutic responses in CRPS.

The researchers acknowledge that their genetic findings could be just one part of the CRPS puzzle. They point out that autoimmune diseases are more prevalent in women than men, and recent studies strongly suggest a causative link between autoimmune disorders and some cases of CRPS.

The findings may be biologically significant, as the genes ANO10, P2RX7, and SLC12A9 are expressed in immune cells in the peripheral nervous system, both of which are involved in the symptoms observed in individuals with CRPS. Additionally, all four genes are typically expressed in macrophages, a type of white blood cell involved in the immune response, in healthy subjects.

It is important to note that this study was observational, meaning that definitive conclusions about cause and effect cannot be drawn. The researchers also acknowledge that the sample sizes were relatively small, potentially limiting the detection of other SNPs. Furthermore, the majority of participants in the study were from the White population.

In conclusion, the study provides evidence supporting a genetic predisposition to CRPS in approximately one-third of cases, with a more pronounced effect in males. Further research on these genes and SNPs could contribute to the development of personalized precision diagnosis and treatment for CRPS.


  1. Source: Coherent Market Insights, Public sources, Desk research
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