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Serum levels of mu-opioid receptor according to menstrual cycle phases are associated with postoperative pain and opioid consumption in laparoscopic gynecological surgeries: a prospective observational study

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Abstract

Aims

In this prospective observational clinical study, we aimed to evaluate the relationship between serum mu-opioid receptor (MOR) levels according to menstrual cycle phases on postoperative pain scores and analgesic requirements.

Methods

A total of 80 female patients undergoing laparoscopic surgery were divided into two groups according to the phases of the menstrual cycle as follicular and luteal. Postoperative pain scores, total tramadol consumptions, and numbers of demands on patient-controlled analgesia (PCA) of the patients were recorded at 5 time points (T0: in the recovery room, T1: 1st hour in the ward, T2: 6th hour in the ward, T3: 12th hour in the ward, T4: 24th hour in the ward). Serum MOR concentrations were measured by enzyme-linked immunosorbent assay.

Results

The mean serum MOR levels were significantly higher in the follicular group (275 ± 32 pg/ml) compared to the luteal group (254 ± 28 pg/ml) (p = 0.003). Total tramadol consumption (T0, T2, and T3) was significantly higher in the luteal group (p = 0.031, p = 0.012, p = 0.017, respectively). Postoperative pain scores did not differ significantly between the groups. With the exception of T4 (p = 0.057), the number of demands on PCA was significantly higher in the luteal group. However, multivariate logistic regression analysis showed that serum MOR levels were affected by the menstrual cycle phase (follicular) (β = 0.361) (p = 0.001).

Conclusions

Our study revealed that patients during the follicular phase with higher serum MOR levels consumed less opioid analgesic postoperatively. More comprehensive studies are needed to determine the relationship between serum MOR levels and menstrual cycle phases as well as postoperative pain. (Trial registration number: NCT04690491 www.clinicaltrials.gov).

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References

  1. Zeeni C, Chamsy D, Khalil A et al (2020) Effect of postoperative Trendelenburg position on shoulder pain after gynecological laparoscopic procedures: a randomized clinical trial. BMC Anesthesiol 20(27):1–7. https://doi.org/10.1186/s12871-020-0946-9

    Article  CAS  Google Scholar 

  2. Wiesenfeld-Hallin Z (2005) Sex differences in pain perception. Gend Med 3(2):137–145

    Article  Google Scholar 

  3. Hussain AM, Khan FA, Ahmed A et al (2013) Effect of gender on pain perception and analgesic consumption in laparoscopic cholecystectomy: an observational study. J Anaesthesiol Clin Pharmacol 29(3):337–341. https://doi.org/10.4103/0970-9185.117095

    Article  PubMed  PubMed Central  Google Scholar 

  4. Lee CWS, Ho IK (2013) Sex differences in opioid analgesia and addiction: interactions among opioid receptors and estrogen receptors. Mol Pain 9(1):1–10

    Google Scholar 

  5. Piroli A, Mattei A, Carta G et al (2019) Influence of the menstrual cycle phase on pain perception and analgesic requirements in young women undergoing gynecological laparoscopy. Pain Pract 19(2):140–148. https://doi.org/10.1111/papr.12727

    Article  PubMed  Google Scholar 

  6. Iacovides S, Avidon I, Baker FC (2015) Does pain vary across the menstrual cycle? A Rev Eur J Pain 19(10):1389–1405. https://doi.org/10.1002/ejp.714

    Article  CAS  PubMed  Google Scholar 

  7. Rezaii T, Hirschberg AL, Carlström K et al (2012) The influence of menstrual phases on pain modulation in healthy women. J Pain 13(7):646–655. https://doi.org/10.1016/j.jpain.2012.04.002

    Article  PubMed  Google Scholar 

  8. Sener EB, Kocamanoglu S, Cetinkaya MB et al (2005) Effects of menstrual cycle on postoperative analgesic requirements, agitation, incidence of nausea and vomiting after gynecological laparoscopy. Gynecol Obstet Invest 59(1):49–53. https://doi.org/10.1159/000081222

    Article  PubMed  Google Scholar 

  9. Jewelewicz R (1984) The role of endogenous opioid peptides in control of the menstrual cycle. Fertil Steril 42(5):683–685

    Article  CAS  PubMed  Google Scholar 

  10. Gencer M, Gocmen AY (2020) The relationship between the level of μ-opioid receptor (μORs) and postoperative analgesic use in patients undergoing septoplasty: a prospective randomized controlled trial. BMC Anesthesiol 20(1):1–15. https://doi.org/10.21203/rs.3.rs-19493/v5

    Article  Google Scholar 

  11. Liang X, Liu R, Chen C et al (2016) Opioid system modulates the immune function: a review. Transl Perioper Pain Med 1(1):5–13

    PubMed  PubMed Central  Google Scholar 

  12. Al-Hakeim H, Al-Fadhel S, Al-Dujaili AH, Maes M (2019) In major depression, increased serum dynorphin and kappa opioid receptor levels are positively associated with mu opioid receptor levels and immune activation and are attenuated by nicotine dependence (April):1–38. Available from: https://doi.org/10.20944/preprints201904.0176.v1

  13. Al-Hakeim HK, Zeki Al-Fadhel S, Al-Dujaili AH, Maes M (2020) In major depression, increased kappa and mu opioid receptor levels are associated with immune activation. Acta Neuropsychiatr 32(2):99–108

    Article  PubMed  Google Scholar 

  14. Almulla AF, Al-Rawi KF, Maes M, Al-Hakeim HK (2021) In schizophrenia, immune-inflammatory pathways are strongly associated with depressive and anxiety symptoms, which are part of a latent trait which comprises neurocognitive impairments and schizophrenia symptoms. J Affect Disord 287:316–326. https://doi.org/10.1016/j.jad.2021.03.062

    Article  CAS  PubMed  Google Scholar 

  15. Al-Fadhel SZ, Al-Hakeim HK, Al-Dujaili AH, Maes M (2019) IL-10 is associated with increased mu-opioid receptor levels in major depressive disorder. Eur Psychiatry 57:46–51. https://doi.org/10.1016/j.eurpsy.2018.10.001

    Article  PubMed  Google Scholar 

  16. Vidal EL, Patel NA, Fiala M et al (1998) Interleukin-1 induces the expression of μ opioid receptors in endothelial cells. Immunopharmacology 1;38(3):261–6

  17. Böttcher B, Seeber B, Leyendecker G, Wildt L (2017) Impact of the opioid system on the reproductive axis. Am Soc Reproduct Med. https://doi.org/10.1016/j.fertnstert.2017.06.009

    Article  Google Scholar 

  18. Totorikaguena L, Olabarrieta E, Matorras R et al (2017) Mu opioid receptor in the human endometrium: dynamics of its expression and localization during the menstrual cycle. Fertil Steril 107(4):1070–1077. https://doi.org/10.1016/j.fertnstert.2017.01.020

    Article  CAS  PubMed  Google Scholar 

  19. Lee J, Lee J, Ko S (2014) The relationship between serum progesterone concentration and anesthetic and analgesic requirements: a prospective observational study of parturients undergoing cesarean delivery. Anesth Analg 119(4):901–905. https://doi.org/10.1213/ANE.0000000000000366

    Article  CAS  PubMed  Google Scholar 

  20. Yang MMH, Hartley RL, Leung AA et al (2019) Preoperative predictors of poor acute postoperative pain control: a systematic review and meta-analysis. BMJ Open 9:e025091. https://doi.org/10.1136/bmjopen-2018-025091

    Article  PubMed  PubMed Central  Google Scholar 

  21. Ring C, Veldhuijzen van Zanten JJCS, Kavussanu M (2009) Effects of sex, phase of the menstrual cycle and gonadal hormones on pain in healthy humans. Biol Psychol 81(3):189–191. https://doi.org/10.1016/j.biopsycho.2009.04.004

    Article  PubMed  Google Scholar 

  22. Xie N, Matigian N, Vithanage T et al (2018) Effect of perioperative opioids on cancer-relevant circulating parameters: mu opioid receptor and toll-like receptor 4 activation potential, and proteolytic profile. Clin Cancer Res 24(10):2319–2327

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would also like to thank all of the staff in the Department of Anesthesiology and Gynecology for their fundamental support during the study (Yozgat Bozok University, Medical Faculty Hospital, Yozgat, Turkey). In addition, the authors are grateful to the anesthesiologists M.D. (Ahmet Yuksek and Cevdet Yardımcı) and anesthesiology residents for their support throughout the study.

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Authors and Affiliations

  1. Department of Anesthesiology and Reanimation, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey

    Ökkeş Hakan Miniksar & Mehtap Honca

  2. Department of Obstetrics and Gynecology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey

    Taylan Onat

  3. Department of Biochemistry, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey

    Ayse Yesim Gocmen

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  1. Ökkeş Hakan Miniksar
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Correspondence to Ökkeş Hakan Miniksar.

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Miniksar, Ö.H., Onat, T., Gocmen, A.Y. et al. Serum levels of mu-opioid receptor according to menstrual cycle phases are associated with postoperative pain and opioid consumption in laparoscopic gynecological surgeries: a prospective observational study. Ir J Med Sci 192, 1847–1854 (2023). https://doi.org/10.1007/s11845-022-03146-z

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