The effect of regional anaesthesia and genetic factors on the development of chronic pain following total knee arthroplasty

Abstract

Background: Chronic Post Surgical Pain (CPSP) is common after Total Knee Arthroplasty (TKA). Factors, including demographic, genetic and possibly anaesthetic techniques, that may modify the risk of developing CPSP are still being investigated. Aim and Objectives: The aims of this study were to show how anaesthetic techniques may influence CPSP and to evaluate potential polymorphisms in six genes that may also affect CPSP. Furthermore, this research studied the genomic variation of these genes in a sample of the local population. The genes investigated were COMT, GCH1, SCN9A, KCNS1, OPRM1 and OPRK1. Methods: Patients scheduled for a TKA were enrolled. Baseline characteristics were obtained, with a blood sample collected for genotyping. Patients were randomized to a spinal anaesthetic alone or to a general anaesthetic with femoral nerve block. Genotyping was performed using TaqManTM SNP Genotyping assays. Patients were followed up at three and at six months with a telephone questionnaire that included a WOMAC® and S-LANSS score. The primary outcome was the WOMAC® score at six months. Secondary outcomes were the acute postoperative pain scores, the WOMAC® Pain score, the S-LANSS score and the incidence of chronic post-surgical pain (CPSP) at six months. Results: 199 patients participated in the study. Patients who received a spinal anaesthetic had better function (WOMAC®: GA: 16.9 vs SP: 14.4, p-value 0.015) and less pain (WOMAC® pain: GA: 3.04 vs SP: 2.69, p-value 0.02) at three months, but not at six months. Overall, 11% of patients had chronic post-surgical pain (CPSP), with Group GA having a higher incidence of (CPSP) at 6 months (OR 4.07, 95CI: 1.33 – 14.59, p-value 0.019). Neuropathic pain was strongly associated with CPSP. Genotyping revealed that most SNPs had a frequency distribution similar to that found in European samples, except for rs998259 and rs3783641 (GCH1) and for rs495491 and rs533586 (OPRM1). Preoperative pain scores were lower in patients who carried the minor allele of rs2075572(OPRM1) (9 vs 11, p-value: <0.001), rs609148 (OPRM1) (9 vs 10, p-value: 0.028) and rs734784 (KCNS1) (9 vs 11, p-value: 0.046). Patients being homozygous for rs495491 (OPRM1) reported lower pain scores at rest (0 vs 2, p-value: 0.05). On multivariate analysis, patients homozygous for rs4633 (COMT) had lower WOMAC® pain scores at six months (Estimate -1.78, 95CI: -2.98 – -0.58, p-value: 0.004). Patients who carried the rs2075572 (OPRM1) had higher pain scores at three months (Estimate: +7.30, 95CI:2.64 – 11.96, p-value: 0.002). Patients who had two copies of rs734784 (KCNS1) had lower WOMAC® scores throughout the study period (Estimate3.94, 95CI: -6.97 – -0.91, p-value: 0.011). Conclusion: Spinal anaesthesia appears to reduce CPSP when compared to general anaesthesia with a femoral block. Genetic polymorphisms may also play a role in the development of CPSP.