Multifocal Analysis of Acute Pain After Third Molar Removal

Giovana Maria Weckwerth, Thiago José Dionísio, Yuri Martins Costa, Paulo Zupelari-Gonçalves, Gabriela Moraes Oliveira, Elza Araújo Torres, Leonardo Rigoldi Bonjardim, Flavio Augusto Cardoso Faria, Adriana Maria Calvo, Troy Moore, Devin Michael Absher, Carlos Ferreira Santos, Giovana Maria Weckwerth, Thiago José Dionísio, Yuri Martins Costa, Paulo Zupelari-Gonçalves, Gabriela Moraes Oliveira, Elza Araújo Torres, Leonardo Rigoldi Bonjardim, Flavio Augusto Cardoso Faria, Adriana Maria Calvo, Troy Moore, Devin Michael Absher, Carlos Ferreira Santos

Abstract

Background: To analyze the pain modulation capacity profile in a Brazilian population, the relationship between opioid receptor (OPRM1) and Catechol-O-methyltransferase (COMT) 1polymorphisms and pain modulation capacity was determined through preoperative pain modulation tests and acute postoperative pain control evaluation, swelling, and trismus in 200 volunteers undergoing lower third molar removal. Methods: Psychologic and clinical parameters were measured. Patient DNA was sequenced for single nucleotide polymorphisms in OPRM1 and COMT, and the salivary concentration of interleukin (IL)-2 (IL)-6, interferon (IFN)-γ and tumor necrosis factor (TNF)-α was evaluated. Primary outcomes were the influence of all predictors on the fluctuation of pain intensity using a visual analogue scale (VAS), and swelling and trismus on the 2nd and 7th postoperative days. Preoperative pain modulation capacity (CPM), pain catastrophizing scale (PCS), body mass index (BMI), and surgery duration and difficulty were evaluated. Results: Salivary concentration of IFN-γ and IL-2 as well as the duration of surgery influenced the fluctuation of postoperative pain in the VAS, and in the sum of the differences in pain intensity test at 8, 48, and 96 h. BMI influenced swelling, while both BMI and COMT haplotype influenced trismus on the 2nd postoperative day. Conclusion: Polymorphisms in COMT, salivary concentrations of IL-2 and IFN-γ, BMI, and duration of surgery were predictors for pain fluctuation, swelling, and trismus on the 2nd day after lower third molar extraction. This therapy was effective in controlling inflammatory symptomatology after lower third molar extraction and ibuprofen was well tolerated by patients. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03169127.

Keywords: NSAIDs (non-steroidal anti-inflammatory drugs); catechol O-methyltransferase (COMT); opioid receptor; pain; polymorphisms.

Conflict of interest statement

TM was employed by the Kailos Genetics Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be considered as a potential conflict of interest.

Copyright © 2021 Weckwerth, Dionísio, Costa, Zupelari-Gonçalves, Oliveira, Torres, Bonjardim, Faria, Calvo, Moore, Absher and Santos.

Figures

FIGURE 1
FIGURE 1
Consort flow diagram (Weckwerth et al., 2020).

References

    1. Akbulut N., Üstüner E., Atakan C., Çölok G. (2014). Comparison of the effect of naproxen, etodolac and diclofenac on postoperative sequels following third molar surgery: a randomised, double-blind, crossover study. Med. Oral Patol Oral Cir. Bucal 19 (2), e149–e156. 10.4317/medoral.19518
    1. Antunes A. A., Avelar R. L., Martins Neto E. C., Frota R., Dias E. (2011). Effect of two routes of administration of dexamethasone on pain, edema, and trismus in impacted lower third molar surgery. Oral Maxillofac. Surg. 15 (4), 217–223. 10.1007/s10006-011-0290-9
    1. Bartošová O., Polaneckỳ O., Perlík F., Adámek S., Slanař O. (2015). OPRM1 and ABCB1 polymorphisms and their effect on postoperative pain relief with piritramide. Physiol. Res. 64, S521–S527. 10.33549/physiolres.933210
    1. Bond C., LaForge K. S., Tian M., Melia D., Zhang S., Borg L., et al. (1998). Single-nucleotide polymorphism in the human mu opioid receptor gene alters β-endorphin binding and activity: possible implications for opiate addiction. Proc. Natl. Acad. Sci. 95 (16), 9608–9613. 10.1073/pnas.95.16.9608
    1. Calvo A. M., Brozoski D. T., Giglio F. P. M., Gonçalves P. Z., Sant’Ana E., Dionísio T. J., et al. (2012). Are antibiotics necessary after lower third molar removal? Oral surg. Oral Med. Oral Pathol. Oral Radiol. 114 (Suppl. 5), S199–S208. 10.1016/j.oooo.2011.10.022
    1. Calvo A. M., Zupelari-Gonçalves P., Dionísio T. J., Brozoski D. T., Faria F. A., Santos C. F. (2017). Efficacy of piroxicam for postoperative pain after lower third molar surgery associated with CYP2C8*3 and CYP2C9. J. Pain Res. 10, 1581–1589. 10.2147/JPR.S138147
    1. Chou W. Y., Yang L. C., Lu H. F., Ko J. Y., Wang C. H., Lin S. H., et al. (2006). Association of μ-opioid receptor gene polymorphism (A118G) with variations in morphine consumption for analgesia after total knee arthroplasty. Acta Anaesthesiol. Scand. 50 (7), 787–792. 10.1111/j.1399-6576.2006.01058.x
    1. Cooper S. A., Beaver W. T. (1976). A model to evaluate mild analgesics in oral surgery outpatients. Clin. Pharmacol. Ther. 20 (2), 241–250. 10.1002/cpt1976202241
    1. Cooper S. A., Desjardins P. J., Turk D. C., Dworkin R. H., Katz N. P., Kehlet H., et al. (2016). Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations. Pain 157, 288–301. 10.1097/j.pain.0000000000000375
    1. Costa Y. M., Morita-Neto O., de Araújo-Júnior E. N. S., Sampaio F. A., Conti P. C. R., Bonjardim L. R. (2017). Test-retest reliability of quantitative sensory testing for mechanical somatosensory and pain modulation assessment of masticatory structures. J. Oral Rehabil. 44 (3), 197–204. 10.1111/joor.12477
    1. Crist R. C., Berrettini W. H. (2014). Pharmacogenetics of OPRM1. Pharmacol. Biochem. Behav. 123, 25–33. 10.1016/j.pbb.2013.10.018
    1. de Oliveira J. C. S., de Oliveira G. A. G., Farnezi Bassi A. P. (2016). Comparative assessment of the effect of ibuprofen and etodolac on edema, trismus, and pain in lower third molar surgery: a randomized clinical trial. J. Oral Maxillofac. Surg. 74 (8), 1524–1530. 10.1016/j.joms.2016.04.003
    1. Degirmenci A., Yalcin E. (2019). The effect of pregabalin and ibuprofen combination for pain after third molar surgery. Niger. J. Clin. Pract. 22 (4), 503–510. 10.4103/njcp.njcp_492_18
    1. Ferrante A. W. (2007). Obesity-induced inflammation: a metabolic dialogue in the language of inflammation. J. Intern. Med. 262 (4), 408–414. 10.1111/j.1365-2796.2007.01852.x
    1. Fillingim R. B., Kaplan L., Staud R., Ness T. J., Glover T. L., Campbell C. M., et al. (2005). The A118G single nucleotide polymorphism of the μ-opioid receptor gene (OPRM1) is associated with pressure pain sensitivity in humans. J. Pain 6 (3), 159–167. 10.1016/j.jpain.2004.11.008
    1. Graziani F., D’Aiuto F., Arduino P. G., Tonelli M., Gabriele M. (2006). Perioperative dexamethasone reduces post-surgical sequelae of wisdom tooth removal. A split-mouth randomized double-masked clinical trial. Int. J. Oral Maxillofac. Surg. 35 (3), 241–246. 10.1016/j.ijom.2005.07.010
    1. Jensen K. B., Lonsdorf T. B., Schalling M., Kosek E., Ingvar M. (2009). Increased sensitivity to thermal pain following a single opiate dose is influenced by the COMT Val158 Met polymorphism. PLoS One 4 (6), 2–6. 10.1371/journal.pone.0006016
    1. Jensen M. P., Martin S. A., Cheung R. (2005). The meaning of pain relief in a clinical trial. J. Pain 6 (6), 400–406. 10.1016/j.jpain.2005.01.360
    1. Kim H., Lee H., Rowan J., Brahim J., Dionne A. R. (2006). Genetic polymorphisms in monoamine neurotransmitter systems show only weak association with acute post-surgical pain in humans. Mol. Pain 2, 1–9. 10.1186/1744-8069-2-24
    1. Lee P. J., Delaney P., Keogh J., Sleeman D., Shorten G. D. (2011). Catecholamine-O-Methyltransferase polymorphisms are associated with postoperative pain intensity. Clin. J. Pain 27 (2), 93–101. 10.1097/ajp.0b013e3181f15885
    1. Liu Y. C., Wang W. S. (2012). Human mu-opioid receptor gene A118G polymorphism predicts the efficacy of tramadol/acetaminophen combination tablets (ultracet) in oxaliplatin-induced painful neuropathy. Cancer 118 (6), 1718–1725. 10.1002/cncr.26430
    1. Lötsch J., Stuck B., Hummel T. (2006). The human μ-opioid receptor gene polymorphism 118A > G decreases cortical activation in response to specific nociceptive stimulation. Behav. Neurosci. 120, 1218–1224. 10.1037/0735-7044.120.6.1218
    1. Martire L. M., Wilson S. J., Brent J. S., Yvette P. C., Piotr K. J., Sliwinski M. J. (2016). COMT and OPRM1 genotype Associations with daily knee pain variability and activity induced pain. Scand. J. Pain 10, 6–12. 10.1016/j.sjpain.2015.07.004
    1. Matsunaga M., Isowa T., Murakami H., Kasugai K., Yoneda M., Kaneko H., et al. (2009). Association of polymorphism in the human μ-opioid receptor OPRM1 gene with proinflammatory cytokine levels and health perception. Brain Behav. Immun. 23 (7), 931–935. 10.1016/j.bbi.2009.03.007
    1. Merksey H., Bogduk N. (1994). “Criteria CRPS,” in Classification of chronic pain. 2nd Edn. Editors Merskey H., Bogduk N. (Seattle, WA: International Association for the Study of Pain; ).
    1. Pérez-González J. M., Esparza-Villalpando V., Martínez-Rider R., Noyola-Frías M. Á., Pozos-Guillén A. (2018). Clinical and radiographic characteristics as predictive factors of swelling and trismus after mandibular third molar surgery: a longitudinal approach. Pain Res. Manage. 2018, 7938492. 10.1155/2018/7938492
    1. Porporatti A., Bonjardim L., Stuginski-Barbosa J., Bonfante E., Costa Y., Rodrigues Conti P. (2017). Pain from dental implant placement, inflammatory pulpitis pain, and neuropathic pain present different somatosensory profiles. J. Oral Facial Pain Headache 31 (1), 19–29. 10.11607/ofph.1680
    1. Santana-Santos T., de Souza-Santos J. A. S., Martins-Filho P. R. S., da Silva L. C. F., de Oliveira E. D., Gomes A. C. A. (2013). Prediction of postoperative facial swelling, pain and trismus following third molar surgery based on preoperative variables. Med. Oral Patol. Oral Cir. Bucal. 18 (1), e65–e70. 10.4317/medoral.18039
    1. Santos C. F., Modena K. C., Giglio F. P. M., Sakai V. T., Calvo A. M., Colombini B. L., et al. (2007). Epinephrine concentration (1:100,000 or 1:200,000) does not affect the clinical efficacy of 4% articaine for lower third molar removal: a double-blind, randomized, crossover study. J. Oral Maxillofac. Surg. 65 (12), 2445–2452. 10.1016/j.joms.2007.04.020
    1. Sehn F., Chachamovich E., Vidor L. P., Dall-Agnol L., Custódio de Souza I. C., Torres I. L. S., et al. (2012). Cross-cultural adaptation and validation of the Brazilian Portuguese version of the pain catastrophizing scale. Pain Med. 13 (11), 1425–1435. 10.1111/j.1526-4637.2012.01492.x
    1. Senagore A. J., Champagne B. J., Dosokey E., Brady J., Steele S. R., Reynolds H. L., et al. (2017). Pharmacogenetics-guided analgesics in major abdominal surgery: further benefits within an enhanced recovery protocol. Am. J. Surg. 213 (3), 467–472. 10.1016/j.amjsurg.2016.11.008
    1. Senes A. M., Calvo A. M., Colombini-Ishikiriama B. L., Gonçalves P. Z., Dionísio T. J., Sant'ana E., et al. (2015). Efficacy and safety of 2% and 4% articaine for lower third molar surgery. J. Dent Res. 94 (Suppl. 9), 166S–173S. 10.1177/0022034515596313
    1. Simoneti L. F., Weckwerth G. M., Dionísio T. J., Zupelari-Gonçalves P., Calvo A. M., Lauris J. R., et al. (2018). Efficacy of ketoprofen with or without omeprazole for pain and inflammation control after third molar removal. Braz. Dent. J. 29 (2), 140–149. 10.1590/0103-6440201802254
    1. Soares F. F. C., Poluha R. L., Canales G. L. T., Costa Y. M., Nascimento G. G., Conti P. C. R., et al. (2020). Genetic polymorphism on pain sensitivity of orofacial region: a systematic review. J. Oral Facial Pain Headache 34, 353–363. 10.11607/ofph.2641
    1. Sullivan M. J. L., Bishop S. R., Pivik J. (1995). The pain catastrophizing scale: development and validation. Psychol. Assess. 7 (4), 524–532. 10.1037/1040-3590.7.4.524
    1. Theken K. N., Hersh E. V., Lahens N. F., Lee H. M., Li X., Granquist E. J., et al. (2019). Variability in the analgesic response to ibuprofen is associated with cyclooxygenase activation in inflammatory pain. Clin. Pharmacol. Ther. 106 (3), 632–641. 10.1002/cpt.1446
    1. Trescot A. M., Datta S., Lee M., Hansen H. (2008). Opioid Pharmacology. Pain Physician 11 (2 Suppl. l), S133–S153.
    1. Trindade P. A. K., Giglio F. P. M., Colombini-Ishikiriama B. L., Calvo A. M., Modena K. C. S., Ribeiro D. A., et al. (2011). Comparison of oral versus sublingual piroxicam during postoperative pain management after lower third molar extraction. Int. J. Oral Maxillofac. Surg. 40 (3), 292–297. 10.1016/j.ijom.2010.10.026
    1. Trindade P. A. K., Giglio F. P. M., Colombini-Ishikiriama B. L., Calvo A. M., Modena K. C. S., Ribeiro D. A., et al. (2012). Sublingual ketorolac and sublingual piroxicam are equally effective for postoperative pain, trismus, and swelling management in lower third molar removal. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 114 (1), 27–34. 10.1016/j.tripleo.2011.05.027
    1. Troullos E. S., Hargreaves K. M., Butler D. P., Dionne R. A. (1990). Comparison of nonsteroidal anti-inflammatory drugs, ibuprofen and flurbiprofen, with methylprednisolone and placebo for acute pain, swelling, and trismus. J. Oral Maxillofacial Surg. 48 (9), 945–952. 10.1016/0278-2391(90)90007-o
    1. Weckwerth G. M., Dionísio T. J., Costa Y. M., Colombini-Ishiquiriama B. L., Oliveira G. M., Torres E. A., et al. (2020). CYP450 polymorphisms and clinical Pharmacogenetics of ibuprofen after lower third molar extraction. Eur. J. Clin. Pharmacol. 22 (1), e122–e131. 10.1007/s00228-020-03046-0
    1. Weckwerth G. M., Simoneti L. F., Zupelari-Goncalves P., Calvo A. M., Brozoski D. T., Dionisio T. J., et al. (2016). Efficacy of naproxen with or without esomeprazole for pain and inflammation in patients after bilateral third molar extractions: a double blinded crossover study. Medicina Oral Patología Oral y Cirugia Bucal 22 (1), e122–e131. 10.4317/medoral.21514
    1. Yarnitsky D. (2015). Role of endogenous pain modulation in chronic pain mechanisms and treatment. Pain 156, S24–S31. 10.1097/01.j.pain.0000460343.46847.58
    1. Zhang Y., Wang D., Johnson A. D., Papp A. C., Sadée W. (2005). Allelic expression imbalance of human mu opioid receptor (OPRM1) caused by variant A118G. J. Biol. Chem. 280 (38), 32618–32624. 10.1074/jbc.m504942200
    1. Zupelari-Goncalves P., Weckwerth G. M., Calvo A. M., Simoneti L. F., Dionisio T. J., Brozoski D. T., et al. (2017). Efficacy of oral diclofenac with or without codeine for pain control after invasive bilateral third molar extractions. Int. J. Oral Maxillofacial Surg. 46 (5), 621–627. 10.1016/j.ijom.2017.01.008

Source: PubMed

3
Abonner