J Biomed Transl Res.  2022 Dec;23(4):109-118. 10.12729/jbtr.2022.23.4.109.

Genetic role in the pathogenesis of complex regional pain syndrome: a review

• Kang H
• Noh S
• Hwang J
• Lee J
• Gang S

• KMID: 2538513
• DOI: http://doi.org/10.12729/jbtr.2022.23.4.109

Abstract

The ambiguity of complex regional pain syndrome (CRPS) posed a challenge to many medical researchers in the early days after its discovery and continues to do so till date. The establishment of the Budapest Criteria of the International Association for the Study of Pain resolved certain queries on CRPS. Many aspects of CRPS, such as pathophysiology and etiology, remain unknown. Therefore, of these aspects, we focused on the genetic basis of CRPS. In this qualitative review, we summarized the recent findings on the genetic associa-tion of CRPS and analyzed the roles of genes identified in each study and limitations of the studies. In particular, we confirmed the reliability of each study by comparing the following research, which used the following control groups or the same candidate genes. Notably, specific phenotypes of CRPS with dystonia indicate a significant association with human leukocyte antigen (HLA)-DQ8. Further, HLA-DQ8, which is associated with aberrant CD4+ T-cell reaction, could be associated with CRPS etiology since an increased CD4+ T-cell population was reported in CRPS patients. In addition, matrix metalloproteinase (MMP)-9 found in genome-wide expression profiling is noteworthy since MMP-9 is associated with neuro-in-flammatory reactions. Despite these suggestions on the genetic aspects of CRPS, the patho-physiology and etiology of CRPS may be polygenic and multifactorial, influenced by multiple genes and other factors. Further, some studies have suggested that CRPS phenotypes have different etiologies. Thus, further studies with the precise classification of CRPS on a unified basis and with a significant number of case groups are required.

Keyword

complex regional pain syndromes; genes; HLA antigens; matrix metalloproteinases; genome