Innate immune and neuronal genetic markers are highly predictive of postoperative pain and morphine patient-controlled analgesia requirements in Indian but not Chinese or Malay hysterectomy patients

Abstract

OBJECTIVE: Pain severity and opioid requirements in the postoperative period show substantial and clinically significant inter-patient variation due mainly to factors such as age, surgery type and duration. Genetic factors have not been adequately assessed except for the neuronal OPRM1 rs1799971 and COMT rs4680, whereas the contribution of innate immune signalling pathway genetics was seldom investigated. SETTING: Hospital surgical ward. SUBJECTS: 107 Indian, 184 Malay and 750 Han Chinese women undergoing total hysterectomy surgery. METHODS: Morphine consumption, pre- and post-operative pain were evaluated in relation to genetic variability comprising 19 SNPs in 14 genes involved in glial activation, inflammatory signalling and neuronal regulation plus OPRM1 (1 SNP) and COMT (3 SNPs). RESULTS: Pre- and post-operative pain and age were associated with increased and decreased morphine consumption, respectively. In Chinese patients, only 8% of the variability in consumption could be explained by these nongenetic and genetic (BDNF, IL1B, IL6R, CRP, OPRM1, COMT, MYD88) factors. However, in Indian patients, 41% of morphine consumption variability could be explained by age (explaining <3%) and variants in OPRM1 rs1799971, CRP rs2794521, TLR4 rs4986790, IL2 rs2069762, COMT rs4818, TGFB1 rs1800469 and IL6R rs8192284 when not controlling for postoperative pain. CONCLUSIONS: This is the highest known value reported for genetic contributions (38%) to morphine use in the acute postoperative pain setting. Our findings highlight the need to incorporate both genetic and non-genetic factors and, consider ethnicity-dependent and non-additive genotypic models, when assessing factors that contribute to variability in opioid use.