• Pain Med · Nov 2021

    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.

    • Daniel T Barratt, Alex T Sia, Ene-Choo Tan, and Andrew A Somogyi.
    • Discipline of Pharmacology, Adelaide Medical School, Faculty of Health & Medical Sciences, University of Adelaide, Adelaide, Australia.
    • Pain Med. 2021 Nov 26; 22 (11): 2648-2660.

    ObjectivePain 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 signaling pathway genetics has seldom been investigated.SettingHospital surgical ward.SubjectsWomen (107 Indian, 184 Malay, and 750 Han Chinese) undergoing total hysterectomy surgery.MethodsMorphine consumption, preoperative pain, and postoperative pain were evaluated in relation to genetic variability comprising 19 single-nucleotide polymorphisms (SNPs) in 14 genes involved in glial activation, inflammatory signaling, and neuronal regulation, plus OPRM1 (1 SNP) and COMT (3 SNPs).ResultsPre- and postoperative 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 without controlling for postoperative pain.ConclusionsThis 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 nongenetic factors and consider ethnicity-dependent and nonadditive genotypic models in the assessment of factors that contribute to variability in opioid use.© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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