Pharmacogenetic aspects of the efficacy of nonsteroidal anti-inflammatory drugs and opioid analgesics for postoperative pain relief after total joint arthroplasty

Objective: to investigate possible associations between genetic, clinical, laboratory, and demographic parameters and the level of pain in the early postoperative (p/o) period, the need for opioid analgesics, and gastrointestinal symptoms in patients who underwent primary total knee (TKR) or hip replacement (THR). Material and methods. Sixty-one patients hospitalized for THR or TKR were included in the study. P/o pain relief was achieved using nonsteroidal anti-inflammatory drugs (NSAIDs) – ketoprofen or ketorolac – with tramadol prescribed "on demand." Pain was assessed in all patients using the numeric rating scale (NRS) on postoperative days 1–5. The amount of opioid analgesics used during hospitalization was recorded. Gene polymorphisms of CYP2C9, CYP2C8, PTGS1, PTGS2, ABCB1, CYP2D6, OPRM1, COMT, and C3orf20 were analyzed using real-time polymerase chain reaction. Results and discussion. Patients with the AC genotype of CYP2C9*3 experienced less intense pain on postoperative day 1 (4.5±1.0 vs. 7.0±2.3; p=0.03) and required fewer opioids during hospitalization (20.0±11.5 vs. 28.0±7.4 morphine equivalent units; p=0.04) compared to those with the AA genotype. Carriers of the CC genotype of the rs1045642 polymorphism of the ABCB1 gene reported less pain on day 5 (1.5±0.7 vs. 3.7±1.2; p=0.04) than those with the CT genotype. Patients with the AA genotype of rs1799971 in the OPRM1 gene required more opioids in p/o period than those with AG + GG genotypes (28.4±7.1 vs. 21.6±9.8 morphine equivalent units; p=0.03). Patients with the GG genotype of rs12496846 in the C3orf20 gene experienced more intense pain on p/o day 4 (6.0±1.41) than those with the AA genotype (2.60±1.50; p=0.002). Conclusion. Following THR and TKR, pain intensity and/or opioid use were associated with patients’ pharmacogenetic profiles in CYP2C9, ABCB1, OPRM1, and C3orf20.