Study of the polymorphism of the ADRB2 molecular structure and its influence on the development of chronic postsurgical pain in children

Authors

DOI:

https://doi.org/10.15574/PS.2023.78.9

Keywords:

chronic pain, children, polymorphism, ADRB2

Abstract

Introduction. Pain is a signal to any aggression that leads to cellular damage and requires a defensive response. Uncontrolled acute perioperative visceral pain can lead to the development of pain chronicity. By studying the characteristics of chronic pain, some scientists have identified relationships with single-nucleotide polymorphisms of the beta2-adrenergic receptor (ADRB2) gene.

Purpose - to study the dependence of pain expression in the postoperative period in children on the polymorphism of the molecular structure of the ADRB2 receptor.

Materials and methods. The study involved 42 children (20 boys and 22 girls) aged 7 to 18 years who were treated in the surgical department in 2020-2022 for acute appendicitis and peritonitis.

Results. Based on the results of examining all the subjects under study, 13 children had the Arg16Gly polymorphism, 15 children had the Arg16Gly polymorphic variant, and 14 children were diagnosed with the homomorphic Gly16Gly polymorphism in the ADRB2. The data obtained confirmed the trend of the preliminary analysis and proved better body response to pain relief and reduced pain intensity in individuals with the Arg16Arg variant of the ADRB2.

Analysis of the dependence between the polymorphism of the ADRB2 molecular structure and Visual Analogue Scale (VAS) scores in children in the postoperative period proved that the presence of Arg in the receptor phenotype had a strong negative correlation with the VAS score on discharge day (r=-0.822, p<0.001), while the presence of Gly in the receptor phenotype had a strong positive correlation with the Visual Analogue Scale score on discharge day (r=0.814, p<0.001). In regression analysis, the presence of Gly in the receptor phenotype was associated with a 1.917-fold increase in the VAS score at hospital discharge (OR: 1.917; 95% CI: 1.448-2.385; р<0.001).

Conclusions. The presence of the homomorphic Arg16Arg variant of the ADRB2 in children who underwent anterior abdominal wall surgery was accompanied by rapid response to analgesics.

The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies.

No conflict of interests was declared by the authors.

References

Aisiku P, Smith WR, McClish DK, Levenson JL, Penberthy LT, Roseff SD et al. (2009). Comparisons of high versus low emergency department utilizers in sickle cell disease. Ann Emerg Med. 53 (5): 587-593. https://doi.org/10.1016/j.annemergmed.2008.07.050; PMid:18926599

Apfelbaum JL, Chen C, Mehta SS, Gan TJ. (2003). Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 97 (2): 534-540. https://doi.org/10.1213/01.ANE.0000068822.10113.9E; PMid:12873949

Bisgaard T, Klarskov B, Rosenberg J, Kehlet H. (2001). Characteristics and prediction of early pain after laparoscopic cholecystectomy. Pain. 90: 261-269. https://doi.org/10.1016/S0304-3959(00)00406-1; PMid:11207398

Caperell K, Pitetti R, Cross KP. (2013). Race and acute abdominal pain in a pediatric emergency department. Pediatrics. 131 (6): 1098-1106. https://doi.org/10.1542/peds.2012-3672; PMid:23690514

Diatchenko L, Anderson AD, Slade GD, Fillingim RB, Shabalina SA, Higgins TJ et al. (2006). Three major haplotypes of the beta2 adrenergic receptor define psychological profile, blood pressure, and the risk for development of a common musculoskeletal pain disorder. Am J Med Genet B Neuropsychiatr Genet. 141B (5): 449-462. https://doi.org/10.1002/ajmg.b.30324; PMid:16741943 PMCid:PMC2570772

Dickinson BD, Head CA, Gitlow S, Osbahr AJ. (2010). Maldynia: pathophysiology and management of neuropathic and maladaptive pain--a report of the AMA Council on Science and Public Health. Pain Med. 11 (11): 1635-1653. https://doi.org/10.1111/j.1526-4637.2010.00986.x; PMid:21044254

Dmytriiev D. (2018). Assessment and treatment of postoperative pain in children. Anaesthesia, Pain & Intensive Care. 22 (3): 392-400.

Elsenbruch S, Icenhour A, Enck P. (2017). Visceral pain: a biopsychological perspective. Neuroforum. 23: 105-110. https://doi.org/10.1515/nf-2017-A029

Gan TJ. (2017). Poorly controlled postoperative pain: prevalence, consequences, and prevention. J Pain Res. 10: 2287-2298. https://doi.org/10.2147/JPR.S144066; PMid:29026331 PMCid:PMC5626380

Gebhart GF, Bielefeldt K. Physiology of visceral pain. (2016). Compr Physiol. 6: 609-633. https://doi.org/10.1002/cphy.c150049; PMid:27783853

Hein L. (2006). Adrenoceptors and signal transduction in neurons. Cell Tissue Res. 326 (2): 541-551. https://doi.org/10.1007/s00441-006-0285-2; PMid:16896948

IASP-PAIN. (2018). International association for the study of Pain. In: IASP Taxonomy. URL: http://www.iasp-pain.org/Education/Content.aspx?ItemNumber=1698#Pain. (accessed June 18, 2018).

Koenen LR, Icenhour A, Forkmann K, Pasler A, Theysohn N, Forsting M et al. (2017). Greater fear of visceral pain contributes to differences between visceral and somatic pain in healthy women. Pain. 158: 1599-1608. https://doi.org/10.1097/j.pain.0000000000000924; PMid:28426553

Kucera TJ, Boezaart AP. (2014). Regional anesthesia does not consistently block ischemic pain: two further cases and a review of the literature. Pain Med. 15: 316-319. https://doi.org/10.1111/pme.12235; PMid:24102987

Kumar N, Thapa D, Gombar S, Ahuja V, Gupta R. (2014). Analgesic efficacy of pre-operative stellate ganglion block on postoperative pain relief: a randomised controlled trial. Anaesthesia. 69: 954-660. https://doi.org/10.1111/anae.12774; PMid:25040168

Litonjua AA, Gong L, Duan QL, Shin J, Moore MJ, Weiss ST et al. (2010). Very important pharmacogene summary ADRB2. Pharmacogenet Genomics. 20 (1): 64-69. https://doi.org/10.1097/FPC.0b013e328333dae6; PMid:19927042 PMCid:PMC3098753

Nicholson R, Dixon AK, Spanswick D, Lee K. (2005). Noradrenergic receptor mRNA expression in adult rat superficial dorsal horn and dorsal root ganglion neurons. Neurosci Lett. 380 (3): 316-321. https://doi.org/10.1016/j.neulet.2005.01.079; PMid:15862909

Niv D, Devor M. (2004). Chronic pain as a disease in its own right. Pain Pract. 4 (3): 179-181. https://doi.org/10.1111/j.1533-2500.2004.04301.x; PMid:17173599

Portenoy RK. (2011). Treatment of cancer pain. Lancet. 377 (9784): 2236-2247. https://doi.org/10.1016/S0140-6736(11)60236-5; PMid:21704873

Rees DC, Williams TN, Gladwin MT. (2010). Sickle-cell disease. Lancet. 376 (9757): 2018-2031. https://doi.org/10.1016/S0140-6736(10)61029-X; PMid:21131035

Reiner S, Ambrosio M, Hoffmann C, Lohse MJ. (2010). Differential signaling of the endogenous agonists at the beta2-adrenergic receptor. J Biol Chem. 285 (46): 36188-36198. https://doi.org/10.1074/jbc.M110.175604; PMid:20837485 PMCid:PMC2975241

Schurman JV, Hunter HL, Friesen CA. (2010). Conceptualization and treatment of chronic abdominal pain in pediatric gastroenterology practice. J Pediatr Gastroenterol Nutr. 50 (1): 32-37. https://doi.org/10.1097/MPG.0b013e3181ae3610; PMid:19915496

Semkovych Ya, Dmytriiev D, Rusak P, Zaporozhan S, Nazarchuk O. (2022). Prevalence of chronic pain after herniorrhaphy, orchiopexy, and bernardi procedure in children. A retrospective-prospective study. Paediatric Surgery (Ukraine). 3 (76): 8-18. https://doi.org/10.15574/PS.2022.76.8

Sikandar S, Dickenson AH. (2012). Visceral Pain - the Ins and Outs, the Ups and Downs. Curr Opin Support Palliat Care. 6: 17-26. https://doi.org/10.1097/SPC.0b013e32834f6ec9; PMid:22246042 PMCid:PMC3272481

Skouen JS, Smith AJ, Warrington NM, O'Sullivan PB, McKenzie L, Pennell CE et al. (2012). Genetic variation in the beta-2 adrenergic receptor is associated with chronic musculoskeletal complaints in adolescents. Eur J Pain. 16 (9): 1232-1242. https://doi.org/10.1002/j.1532-2149.2012.00131.x; PMid:22416031

The Ministry of Ukraine. (2004). On Approval of Protocols for Treatment of Children in Specialty Pediatric Surgery. Order of the Ministry of Ukraine No. 88-Adm of March 30, 2004, with amendments and additions made by the Order of the Ministry of Ukraine No. 150 dated February 18, 2010.

Tolver MA, Rosenberg J, Bisgaard T. (2012). Early pain after laparoscopic inguinal hernia repair. A qualitative systematic review. Acta Anaesthesiol Scand. 56 (5): 549-557. https://doi.org/10.1111/j.1399-6576.2011.02633.x; PMid:22260427

Woolf CJ. (2020). Capturing novel non-opioid pain targets. Biol Psychiatry. 87 (1): 74-81. https://doi.org/10.1016/j.biopsych.2019.06.017; PMid:31399256 PMCid:PMC6898770

Wu CL, Raja SN. (2011). Treatment of acute postoperative pain. Lancet. 377 (9784): 2215-2225. https://doi.org/10.1016/S0140-6736(11)60245-6; PMid:21704871

Yalcin I, Tessier LH, Petit-Demouliere N, Waltisperger E, Hein L, Freund-Mercier MJ et al. (2010). Chronic treatment with agonists of beta (2)-adrenergic receptors in neuropathic pain. Exp Neurol. 221 (1): 115-121. https://doi.org/10.1016/j.expneurol.2009.10.008; PMid:19840789

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Published

2023-03-28

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Original articles. General surgery