Cold pain sensitivity is associated with single-nucleotide polymorphisms of PAR2/F2RL1 and TRPM8

Pain sensitivity differs individually, but the mechanisms and genetic factors that underlie these differences are not fully understood. To investigate genetic factors that are involved in sensing cold pain, we applied a cold-induced pain test and evaluated protease-activated receptor 2 (PAR2/F2RL1) and transient receptor potential melastatin 8 (TRPM8), which are related to pain. We statistically investigated the associations between genetic polymorphisms and cold pain sensitivity in 461 healthy patients who were scheduled to undergo cosmetic orthognathic surgery for mandibular prognathism. We found an association between cold pain sensitivity and the rs2243057 polymorphism of the PAR2 gene. We also found a significant association between cold pain sensitivity and the rs12992084 polymorphism of the TRPM8 gene. Carriers of the minor A allele of the rs2243057 polymorphism of PAR2 and minor C allele of the rs12992084 polymorphism of TRPM8 exhibited a longer latency to pain perception in the cold-induced pain test, reflecting a decrease in cold pain sensitivity. These results suggest that genetic polymorphisms of both PAR2 and TRPM8 are involved in individual differences in cold pain sensitivity.