Single-Nucleotide Polymorphisms of the PAR2 and IL-17A Genes Are Significantly Associated with Chronic Pain.

Patients with chronic pain are affected psychologically and socially. There are also individual differences in treatment efficacy. Insufficient research has been conducted on genetic polymorphisms that are related to individual differences in the susceptibility to chronic pain. Autoimmune disorders can lead to inflammation and chronic pain; therefore, we focused on the autoimmune-related protease-activated receptor 2 (PAR2/F2RL1) and interleukin 17A (IL-17A/IL17A) genes. PAR2 and IL-17A are associated with autoimmune diseases that lead to chronic pain, and PAR2 regulates T-helper (Th) cell activation and differentiation. We hypothesized that the PAR2 and IL-17A genes are associated with chronic pain. The present study used a case-control design to statistically examine associations between genetic polymorphisms and the vulnerability to chronic pain. The rs2243057 polymorphism of the PAR2 gene and rs3819025 polymorphism of the IL-17A gene were previously reported to be associated with pain- or autoimmune-related phenotypes. Thus, these polymorphisms were investigated in the present study. We found that both rs2243057 and rs3819025 were significantly associated with a susceptibility to chronic pain. The present findings revealed autoimmune-related genetic factors that are involved in individual differences in chronic pain, further aiding understanding of the pathomechanism that underlies chronic pain and possibly contributing to future personalized medicine.

Rs11726196 Single-Nucleotide Polymorphism of the Transient Receptor Potential Canonical 3 (TRPC3) Gene Is Associated with Chronic Pain.

Chronic pain is reportedly associated with the transient receptor potential canonical 3 (TRPC3) gene. The present study examined the genetic associations between the single-nucleotide polymorphisms (SNPs) of the TRPC3 gene and chronic pain. The genomic samples from 194 patients underwent linkage disequilibrium (LD) analyses of 29 SNPs within and around the vicinity of the TRPC3 gene. We examined the associations between the SNPs and the susceptibility to chronic pain by comparing the genotype distribution of 194 patients with 282 control subjects. All SNP genotype data were extracted from our previous whole-genome genotyping results. Twenty-nine SNPs were extracted, and a total of four LD blocks with 15 tag SNPs were observed within and around the TRPC3 gene. We further analyzed the associations between these tag SNPs and chronic pain. The rs11726196 SNP genotype distribution of patients was significantly different from the control subjects even after multiple-testing correction with the number of SNPs. The TT + TG genotype of rs11726196 is often carried by chronic pain patients, suggesting a causal role for the T allele. These results contribute to our understanding of the genetic risk factors for chronic pain.

Heparan sulfate 3-O-sulfotransferase 4 is genetically associated with herpes zoster and enhances varicella-zoster virus-mediated fusogenic activity.

Acute pain that is associated with herpes zoster (HZ) can become long-lasting neuropathic pain, known as chronic post-herpetic neuralgia (PHN), especially in the elderly. HZ is caused by the reactivation of latent varicella-zoster virus (VZV), whereas PHN is not attributed to ongoing viral replication. Although VZV infection reportedly induces neuronal cell fusion in humans, the pathogenesis of PHN is not fully understood. A genome-wide association study (GWAS) revealed significant associations between PHN and the rs12596324 single-nucleotide polymorphism (SNP) of the heparan sulfate 3-O-sulfotransferase 4 (HS3ST4) gene in a previous study. To further examine whether this SNP is associated with both PHN and VZV reactivation, associations between rs12596324 and a history of HZ were statistically analyzed using GWAS data. HZ was significantly associated with the rs12596324 SNP of HS3ST4, indicating that HS3ST4 is related to viral replication. We investigated the influence of HS3ST4 expression on VZV infection in cultured cells. Fusogenic activity after VZV infection was enhanced in cells with HS3ST4 expression by microscopy. To quantitatively evaluate the fusogenic activity, we applied cytotoxicity assay and revealed that HS3ST4 expression enhanced cytotoxicity after VZV infection. Expression of the VZV glycoproteins gB, gH, and gL significantly increased cytotoxicity in cells with HS3ST4 expression by cytotoxicity assay, consistent with the fusogenic activity as visualized by fluorescence microscopy. HS3ST4 had little influence on viral genome replication, revealed by quantitative real-time polymerase chain reaction. These results suggest that HS3ST4 enhances cytotoxicity including fusogenic activity in the presence of VZV glycoproteins without enhancing viral genome replication.

Genome-wide association study identifies candidate loci associated with chronic pain and postherpetic neuralgia.

BACKGROUND: Human twin studies and other studies have indicated that chronic pain has heritability that ranges from 30% to 70%. We aimed to identify potential genetic variants that contribute to the susceptibility to chronic pain and efficacy of administered drugs. We conducted genome-wide association studies (GWASs) using whole-genome genotyping arrays with more than 700,000 markers in 191 chronic pain patients and a subgroup of 89 patients with postherpetic neuralgia (PHN) in addition to 282 healthy control subjects in several genetic models, followed by additional gene-based and gene-set analyses of the same phenotypes. We also performed a GWAS for the efficacy of drugs for the treatment of pain. RESULTS: Although none of the single-nucleotide polymorphisms (SNPs) were found to be genome-wide significantly associated with chronic pain (p ≥ 1.858 × 10-7), the GWAS of PHN patients revealed that the rs4773840 SNP within the ABCC4 gene region was significantly associated with PHN in the trend model (nominal p = 1.638 × 10-7). In the additional gene-based analysis, one gene, PRKCQ, was significantly associated with chronic pain in the trend model (adjusted p = 0.03722). In the gene-set analysis, several gene sets were significantly associated with chronic pain and PHN. No SNPs were significantly associated with the efficacy of any of types of drugs in any of the genetic models. CONCLUSIONS: These results suggest that the PRKCQ gene and rs4773840 SNP within the ABCC4 gene region may be related to the susceptibility to chronic pain conditions and PHN, respectively.

Preoperative detection of pleural adhesions using pocket-sized ultrasound.

BACKGROUND: Although preoperative detection of pleural adhesions is important in thoracic surgery, it is not widely performed. We report the availability of a pocket-sized ultrasound device for the preoperative detection of pleural adhesions. METHODS: Between September 2019 and September 2020, pleural adhesions were assessed preoperatively using a pocket-sized ultrasound device in 62 patients who underwent thoracic surgery. Evaluations were performed using the Vscan Dual Probe on the wards or just before surgery in the operating theater. We used a linear probe to scan the chest wall where the incision was scheduled, and evaluated the sliding sign. We compared ultrasound results with intraoperative findings. RESULTS: Of the 62 patients, the sliding sign was observed in 58 patients, 56 of whom demonstrated no pleural adhesions intraoperatively. The sensitivity was 96.6%. Four patients were negative for the sliding sign; of these, three had pleural adhesions and one did not. The specificity was 75.0%. Among all 62 patients, the diagnostic accuracy of ultrasound for pleural adhesions was 95.2%. False negatives were caused by loose adhesions. False positives were caused by the absence of vertical lines on ultrasound. Accuracy was not influenced by the timing of the test. CONCLUSIONS: A pocket-sized ultrasound device was useful for the preoperative detection of pleural adhesions in thoracic surgery.

[A Case of Advanced Gastric Cancer Responding Effectively to Neoadjuvant Chemotherapy].

A 78-year-old man underwent an upper gastrointestinal endoscopy for evaluation of epigastralgia. Endoscopy revealed a bulky type 3 tumor in the lesser curvature of the upper body. A biopsy showed a poorly differentiated adenocarcinoma with signet ring cell carcinoma. Additionally, abdominal computed tomography(CT)showed bulky lymph node metastases leading to a diagnosis of cT3N2M0, Stage III A carcinoma. Following administration of 2 courses of neoadjuvant chemotherapy (NAC)using S-1/cisplatin(CDDP), CT revealed significant regression of the primary lesion and lymph nodes. Eventually, laparoscopic total gastrectomy was performed. Histopathologically, almost all viable cancer cells had been cleared from the primary lesion, and no cancer cells were found in the lymph nodes, which indicated a pathological partial response(Grade 2). NAC could be a valid option for the treatment of advanced gastric cancer.