Genetic Contribution in Low Back Pain: A Prospective Genetic Association Study

• DOI: 10.1111/papr.12816
• Publication Date: 2019-07-03T18:42:51Z
• Authors: César Margarit; Reyes Roca; María‐del‐Mar Inda; Javier Muriel; Pura Ballester; Rocío Moreu; Anna Lucia Conte; Angela Nuñez; Domingo Morales; Ana M Peiró
• Keywords: Adult; Male; OPRM1; ATP Binding Cassette Transporter, Subfamily B; COMT , KCNJ6 , OPRM1 , UGT2B7 , chronic low back pain, opioids, pharmacogenetics; Receptors, Opioid, mu; Polymorphism, Single Nucleotide; 03 medical and health sciences; CDU::6 - Ciencias aplicadas::61 - Medicina::615 - Farmacología. Terapéutica. Toxicología. Radiología; 0302 clinical medicine; KCNJ6; Humans; Prospective Studies; UGT2B7; Genetic Association Studies; pharmacogenetics; Aged; opioids; Middle Aged; COMT; 3. Good health; Analgesics, Opioid; Pharmacogenetics; chronic low back pain; Quality of Life; Female; Chronic Pain; Low Back Pain; Follow-Up Studies

AbstractObjectivesChronic pain is one of the most common reasons individuals seek medical attention. It is a major issue because of the wide interindividual variability in the analgesic response. This might be partly explained by the presence of variants in genes encoding molecules involved in pharmacodynamics and pharmacokinetics. The aim was to analyze opioid effectiveness in chronic low back pain (CLBP) relief after opioid titration, unveiling the impact of pharmacogenetics.MethodsThe study included 231 opioid‐naïve patients from the Spine Unit; age 63 ± 14 years, 64% female, body mass index 29 ± 6 kg/m2, visual analog scale pain intensity score 73 ± 16 mm. Clinical data were collected at baseline, 3 months after opioid titration, and after 2 to 4 years of follow‐up concerning pain (intensity and relief), quality of life, disability, comorbidities, and drug prescription (opioid dose, rotations, and adverse events). The genotype influence ofOPRM1,COMT,UGT2B7,ABCB1,KCNJ6, andCYP3A5*3Ain analgesic response was analyzed by reverse‐transcription polymerase chain reaction genotyping.ResultsPatients with theCOMTG472A‐AAgenotype (rs4680) andKCNJ6A1032G‐A allele (rs2070995)CLBPresponded differently to opioid titration, with higher pain intensity requiring higher dosing. Furthermore,GG‐ genotypes of A118G (OPRM1, rs1799971) and A854G (UGT2B7, rs776746) influenced the neuropathic component. After opioid titration,CLBPintensity, neuropathic component, low back pain disability, anxiety, and depression significantly decreased, while quality of life improved.ConclusionSingle‐nucleotide polymorphisms in genes involved in pain transmission and opioid metabolism might predispose to exaggerated sensitivity and differences in the opioid analgesic effect in patients withCLBP. We encourage clinical trials for their clinical application in chronic pain management.