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Chronic persistent surgical pain is strongly associated with COMT alleles in patients undergoing cardiac surgery with median sternotomy

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Abstract

Objectives

Catechol-O-methyl transferase (COMT), a catechol-dependent enzyme, plays pivotal role in the development of pain. In different ethnic populations, it is associated with chronic persistent surgical pain (CPSP). In this context, the present study is aimed to assess involvement of COMT allele (Val158Met) in the development of CPSP.

Methodology

The patients (n = 216) underwent cardiac surgery with median sternotomy were selected to assess the magnitude of the CPSP evaluated with pain questionnaires’ after 3 months from surgery. The exon 4 of COMT gene was PCR amplified and sequenced. The quantitative gene expression of COMT using RT-PCR corroborated the COMT enzyme activity.

Results

Among 216 patients who underwent sternotomy procedure, 54 patients showed CPSP even after 3 months from surgery. The sequence analysis revealed that, in 25% (54/216) patients having following one or more alleles: c.472G>A (Val158Met) (reported), and novel c.382C>G;c.383G>C (Arg128Ala), c.373C>G (Arg125Gly), c.370G>A (Val124Met), c.359G>C (Gly120Ala), c.349G>A, c.350G>A(Ala117Ser), c.349G>C, c.351C>A (Ala117Pro), c.349G>A (Ala117Thr), c.350G>C (Ala117Gly), and c.405G>C (Ala135Ser) were observed for the first time in Indian population. Distinct CPSP (≥ 4 NRS pain score) was observed in these patients correlating with COMT enzyme activity (7.80 ± 0.92 units/mg) which is 14 times lowered when compared with non-CPSP patient’s (n = 162) 110.15 ± 6.41 units/mg. The findings of COMT gene expression using quantitative RT-PCR corroborated the COMT enzyme activity.

Conclusion

The dominant effect of mutant COMT alleles connecting with low enzyme activity resulted in CPSP, warrants COMT genetic analysis prior to surgery was useful to predict the occurrence of CPSP.

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Acknowledgements

We sincerely acknowledge the Sri Venkateswara Institute of Medical Sciences (SVIMS University), Tirupati, India, for providing the facilities to carry out this work and this paper forms part of a Ph.D. thesis to be submitted to SVIMS University, Tirupati, and Andhra Pradesh, India. This work, carried out in the Department of Anesthesiology, Cardio Thoracic Vascular Surgery and Biotechnology, further supported by the Sri Balaji Arogya Vara Prasadini scheme [SBAVP-RG/Ph.D/20, 2017] from the SVIMS University.

Funding

Sri Balaji Arogya Vara Prasadini scheme [SBAVP-RG/Ph.D/20, 2017] from the SVIMS University.

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Authors and Affiliations

  1. Department of Anesthesiology, SVIMS University, Tirupati, Andhra Pradesh, 517507, India

    Goduguchintha Dharaniprasad, Aloka Samantaray & Mangu Hanumantha Rao

  2. Department of Biotechnology, SVIMS University, Tirupati, Andhra Pradesh, India

    Lokanathan Srikanth & Potukuchi Venktata Gurunadha Krishna Sarma

  3. Department of C.T. Surgery, SVIMS University, Tirupati, Andhra Pradesh, India

    Abha Chandra

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  1. Goduguchintha Dharaniprasad
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Correspondence to Aloka Samantaray.

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Institutional ethics committee (IEC approval no. 614. dated 24.04.2017) at SVIMS and registered under Clinical Trials Registry, India (ICMR-NIMS) (CTRI) with a registration number: CTRI/2018/03/012364.

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Dharaniprasad, G., Samantaray, A., Srikanth, L. et al. Chronic persistent surgical pain is strongly associated with COMT alleles in patients undergoing cardiac surgery with median sternotomy. Gen Thorac Cardiovasc Surg 68, 1101–1112 (2020). https://doi.org/10.1007/s11748-020-01321-6

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