Research Article

* Author for correspondence

Clinical Anaesthesia & Paediatrics, Acute & Perioperative Pain Service, Department of Anaesthesia, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, MLC 2001, Cincinnati, OH 45229, USA.

Email the corresponding author at senthilkumar.sadhasivam@cchmc.org

Vidya Chidambaran

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Vanessa A Olbrecht

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Hope R Esslinger

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Kejian Zhang

Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45040, USA

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Xue Zhang

Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45040, USA

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Lisa J Martin

Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45040, USA

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Published Online:17 Feb 2014https://doi.org/10.2217/pgs.13.248

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Abstract

Background: Effective perioperative analgesia is lacking for children owing to interindividual variations and underdosing of opioids caused by fear of adverse effects. We investigated the role of COMT SNPs on postoperative pain management in children. Methods: One hundred and forty nine children undergoing adenotonsillectomy were enrolled. The associations of four COMT SNPs (rs6269, rs4633, rs4818 and rs4680) with postoperative pain were analyzed and outcome measures included maximum pain scores, need for postoperative opioid interventions and postoperative morphine requirements. Results: We detected an association of postoperative opioid intervention need with all four COMT SNPs. Minor allele carriers of COMT SNPs were approximately three-times more likely to require analgesic interventions than homozygotes of major alleles (p-value range: 0.0031–0.0127; odds ratio range: 2.6–3.1). In addition, significant association was detected between maximum Face, Leg, Activity, Consolability, Cry (FLACC) pain scores and three COMT SNPs (rs6269, rs4633 and rs4680). Haplotype 1 (ATCA: 51.3%) and Haplotype 2 (GCGG: 36.2%) are more frequent. Haplotype 2 was associated with higher odds of intravenous analgesic intervention need in postanesthesia recovery unit with an odds ratio of 2.6 (95% CI: 1.2–5.4; p-value = 0.022). Conclusion:COMT SNPs may play a significant role in interindividual variation in postoperative pain perception and postoperative morphine requirements in children.

Original submitted 16 August 2013; Revision submitted 13 December 2013

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References

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Vol. 15, No. 3

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History

Published online 17 February 2014

Published in print February 2014

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Keywords

Trial registration

This clinical trial reflects a portion of a larger study, Personalizing Perioperative Morphine Analgesia in Children, NCT01140724, registered at clinicaltrials.gov.

Authors’ contribution

S Sadhasivam conceptualized and designed the study, designed the data collection instruments, recruited subjects, and coordinated and supervised data collection, drafted the initial manuscript, and approved the final manuscript as submitted. V Olbrecht helped with the initial draft, reviewed and revised the manuscript, and approved the final manuscript as submitted. V Chidambaran helped with recruitment, reviewed and revised the manuscript, and approved the final manuscript as submitted. HR Esslinger helped with patient recruitment, data collection and approved the final manuscript. K Zhang helped with genetic study design and analysis. X Zhang helped with data analyses, draft statistical section, tables and revision of the manuscript. LJ Martin helped with data analyses, statistical methods, revision of the manuscript and approved the final manuscript as submitted.

Financial & competing interests disclosure

This work was supported in part by USPHS Grant #UL1 RR026314 from the National Center for Research Resources, NIH and with the Place Outcomes Research Award and Translational Research Award, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA. Additional research funding support was provided by the Department of Anesthesia, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA. No financial support was received except for departmental salary support for the authors. This pharmacogenetic study was designed and undertaken by the authors. The sponsor of this study, the Cincinnati Children’s Hospital Medical Center (CCHMC) provided funding support for the genetic analyses and supported the salary of the research team. The authors directed and had access to all the analyses and the full clinical and genetic database, wrote all drafts of the report, decided to publish the results, and attest for the accuracy and completeness of the data. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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Genetics of pain perception, COMT and postoperative pain management in children

Abstract

References