Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Women's Health
Published in: BMC Women's Health 1/2024

Open Access 01-12-2024 | Endometriosis | Research

CGRP neuropeptide levels in patients with endometriosis-related pain treated with dienogest: a comparative study

Authors: Shahla Chaichian, Ziba Dehghan Firoozabadi, Samaneh Rokhgireh, Kobra Tahermanesh, Abolfazl Mehdizadeh Kashi, Azam Govahi, Sara Minaeian, Mehdi Mehdizadeh, Marziyeh Ajdary

Published in: BMC Women's Health | Issue 1/2024

Login to get access

Abstract

Background and objective

Endometriosis (EM) involves the peripheral nervous system and causes chronic pain. Sensory nerves innervating endometriotic lesions contribute to chronic pain and influence the growth phenotype by releasing neurotrophic factors and interacting with nearby immune cells. Calcitonin gene-related peptide (CGRP), a pain-signaling neurotransmitter, has a significant role. This study examines the effect of Dienogest (DNG), a hormone therapy used for managing EM -related pain, on serum CGRP levels in EM patients.

Materials and methods

The Visual Analog Scale (VAS) assessed pain in diagnosed EM. individuals. Serum samples were obtained to measure CGRP concentration. Participants received a 2 mg/day oral dose of DNG for six months as prescribed treatment. Additional serum samples were collected after this period to measure CGRP levels.

Results

In the EM group, 6.7%, 33.3%, and 20% had ovarian EM, ovarian plus uterosacral, and ovarian plus bladder, respectively. The EM group showed higher CGRP serum levels than the control group (80.53 ± 16.13 vs. 58.55 ± 6.93, P < 0.0001). Still, after drug administration, CGRP serum levels significantly decreased compared to pre-treatment levels (69.66 ± 11.53 vs. 80.53 ± 16.13, P < 0.05). The EM group showed higher pain compared to the control group (7.93 ± 1.58 vs. 0.13 ± 0.35, P < 0.0001), but after drug administration, pain significantly decreased compared to pre-treatment levels (1.00 ± 2.00 vs. 7.93 ± 1.58, P < 0.05).

Conclusion

DNG administration reduces pain and serum CGRP levels in EM patients, offering the potential for innovative treatments and tailored options. Understanding neurotransmitter roles and drug effects can aid in discovering more effective modulators for these pathways.
Literature
1.
Bulun SE, Monsavais D, Pavone ME, Dyson M, Xue Q, Attar E, Tokunaga H, Su EJ. Role of estrogen receptor-β in endometriosis. Seminars in reproductive medicine: 2012. Thieme Medical; 2012. pp. 39–45.
2.
Burch RC, Buse DC, Lipton RB. Migraine: epidemiology, burden, and comorbidity. Neurol Clin. 2019;37(4):631–49.CrossRefPubMed
3.
4.
Rahmioglu N, Mortlock S, Ghiasi M, Møller PL, Stefansdottir L, Galarneau G, Turman C, Danning R, Law MH, Sapkota Y. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions. Nat Genet. 2023;55(3):423–36.CrossRefPubMedPubMedCentral
5.
6.
Dutta S, Sengupta P. The role of nitric oxide on male and female reproduction. Malaysian J Med Sciences: MJMS. 2022;29(2):18.
7.
Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain. 2006;10(4):287–333.CrossRefPubMed
8.
Wall MS. Melzack’s Textbook of Pain. /SB McMahon, M. Koltzenburg. In. Elsevier Churchill Livingstone; 2005.
9.
Greenspan JD, Craft RM, LeResche L, Arendt-Nielsen L, Berkley KJ, Fillingim RB, Gold MS, Holdcroft A, Lautenbacher S, Mayer EA. Studying sex and gender differences in pain and analgesia: a consensus report. Pain. 2007;132:S26–45.CrossRefPubMedPubMedCentral
10.
Aloisi AM, Affaitati G, Ceccarelli I, Fiorenzani P, Lerza R, Rossi C, Pace MC, Chiefari M, Aurilio C, Giamberardino MA. Estradiol and testosterone differently affect visceral pain-related behavioural responses in male and female rats. Eur J Pain. 2010;14(6):602–7.CrossRefPubMed
11.
Aloisi AM, Sorda G. Relationship of female sex hormones with pain perception: focus on estrogens. Pain Manage. 2011;1(3):229–38.CrossRef
12.
Russell FA, King R, Smillie S-J, Kodji X, Brain S. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev. 2014;94(4):1099–142.CrossRefPubMedPubMedCentral
13.
Brain SD, Grant AD. Vascular actions of calcitonin gene-related peptide and adrenomedullin. Physiol Rev. 2004;84(3):903–34.CrossRefPubMed
14.
Spencer NJ, Kyloh M, Duffield M. Identification of different types of spinal afferent nerve endings that encode noxious and innocuous stimuli in the large intestine using a novel anterograde tracing technique. PLoS ONE. 2014;9(11):e112466.CrossRefPubMedPubMedCentral
15.
Donnerer J, Stein C. Evidence for an increase in the release of CGRP from sensory nerves during inflammation a. Ann N Y Acad Sci. 1992;657(1):505–6.CrossRefPubMed
16.
Belinskaia M, Zurawski T, Kaza SK, Antoniazzi C, Dolly JO, Lawrence GW. NGF enhances CGRP release evoked by capsaicin from rat trigeminal neurons: Differential inhibition by SNAP-25-cleaving proteases. Int J Mol Sci. 2022;23(2):892.CrossRefPubMedPubMedCentral
17.
Vita D, degli Uberti EC. Changes of plasma calcitonin gene–related peptide levels in postmenopausal women. Am J Obstet Gynecol. 1996;175(3):638–42.CrossRefPubMed
18.
Fattori V, Zaninelli TH, Rasquel-Oliveira FS, Heintz OK, Jain A, Sun L, Seshan ML, Peterse D, Lindholm AE, Anchan RM. Nociceptor to macrophage communication through CGRP/RAMP1 signaling drives endometriosis-associated pain and lesion growth. bioRxiv 2023:2023.2008. 2028.555101.
19.
Velho RV, Sehouli J, Mechsner S. Mechanisms of peripheral sensitization in endometriosis patients with peritoneal lesions and acyclical pain. Arch Gynecol Obstet. 2023;308(4):1327–40.CrossRefPubMedPubMedCentral
20.
Strowitzki T, Marr J, Gerlinger C, Faustmann T, Seitz C. Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial. Hum Reprod. 2010;25(3):633–41.CrossRefPubMed
21.
Durham PL. CGRP-receptor antagonists—a fresh approach to migraine therapy? N Engl J Med. 2004;350(11):1073–5.CrossRefPubMed
22.
Adewuyi EO, Sapkota Y, Auta A, Yoshihara K, Nyegaard M, Griffiths LR, Montgomery GW, Chasman DI, Nyholt DR, Consortium IE. Shared molecular genetic mechanisms underlie endometriosis and migraine comorbidity. Genes. 2020;11(3):268.CrossRefPubMedPubMedCentral
23.
Cooper D, Laidig WD, Sappington A, MacGregor G, Laidig W. A pharmacological review of calcitonin gene-related peptide Biologics and Future Use for Chronic Pain. Cureus 2023, 15(2).
24.
Suttle A, Wang P, Dias FC, Zhang Q, Luo Y, Simmons L, Bortsov A, Tchivileva IE, Nackley AG, Chen Y. Sensory neuron-TRPV4 modulates temporomandibular disorder pain via CGRP in mice. The journal of pain 2022.
25.
Christensen SL, Rasmussen RH, Ernstsen C, La Cour S, David A, Chaker J, Haanes KA, Christensen ST, Olesen J, Kristensen DM. CGRP-dependent signalling pathways involved in mouse models of GTN-cilostazol-and levcromakalim-induced migraine. Cephalalgia. 2021;41(14):1413–26.CrossRefPubMed
26.
Yao G, Man Y-H, Li A-R, Guo Y, Dai Y, Wang P, Zhou Y-F. NO up-regulates migraine-related CGRP via activation of an Akt/GSK-3β/NF-κB signaling cascade in trigeminal ganglion neurons. Aging. 2020;12(7):6370.CrossRefPubMedPubMedCentral
27.
Lykke L, Ernst C, Bek T. The vasoactive effects of bradykinin, vasoactive intestinal peptide, calcitonin gene-related peptide and neuropeptide Y depend on the perivascular tissue in porcine retinal arterioles in vitro. Acta Ophthalmol 2023.
28.
Zhang H, Zhang Xm Z, Dd J, Xy, Jiang H, Zhang Fz H, Sd. miR-34a‐5p up‐regulates the IL‐1β/COX2/PGE2 inflammation pathway and induces the release of CGRP via inhibition of SIRT1 in rat trigeminal ganglion neurons. FEBS Open Bio. 2021;11(1):300–11.CrossRefPubMed
29.
Durham PL, Russo AF. Stimulation of the calcitonin gene-related peptide enhancer by mitogen-activated protein kinases and repression by an antimigraine drug in trigeminal ganglia neurons. J Neurosci. 2003;23(3):807–15.CrossRefPubMedPubMedCentral
30.
Wang Q, Ma T, Lu Z, Liu M, Wang L, Zhao S, Zhao Y. Xiongzhi Dilong decoction interferes with calcitonin gene-related peptide (CGRP)-induced migraine in rats through the CGRP/iNOS pathway. J Traditional Chin Med Sci. 2022;9(3):267–76.CrossRef
31.
Tapmeier TT, Rahmioglu N, Lin J, De Leo B, Obendorf M, Raveendran M, Fischer OM, Bafligil C, Guo M, Harris RA et al. Neuropeptide S receptor 1 is a nonhormonal treatment target in endometriosis. Science translational medicine 2021, 13(608).
32.
Possover M, Tersiev P, Angelov DN. Comparative study of the neuropeptide-Y sympathetic nerves in endometriotic involved and noninvolved sacrouterine ligaments in women with pelvic endometriosis. J Minim Invasive Gynecol. 2009;16(3):340–3.CrossRefPubMed
33.
Raffaelli B, Overeem LH, Mecklenburg J, Hofacker MD, Knoth H, Nowak CP, Neeb L, Ebert AD, Sehouli J, Mechsner S. Plasma calcitonin gene-related peptide (CGRP) in migraine and endometriosis during the menstrual cycle. Ann Clin Transl Neurol. 2021;8(6):1251–9.CrossRefPubMedPubMedCentral
34.
Pota V, Quagliariello V, Armenia E, Aurilio C, Passavanti MB, Sansone P, Iannotti M, Catauro M, Coaccioli S, Barbarisi M. CGRP and visceral pain: the role of sex hormones in in vitro experiment. J Cell Biochem. 2017;118(3):510–7.CrossRefPubMed
Metadata
Title
CGRP neuropeptide levels in patients with endometriosis-related pain treated with dienogest: a comparative study
Authors
Shahla Chaichian
Ziba Dehghan Firoozabadi
Samaneh Rokhgireh
Kobra Tahermanesh
Abolfazl Mehdizadeh Kashi
Azam Govahi
Sara Minaeian
Mehdi Mehdizadeh
Marziyeh Ajdary
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Women's Health / Issue 1/2024
Electronic ISSN: 1472-6874
DOI
https://doi.org/10.1186/s12905-024-03095-y

Other articles of this Issue 1/2024

BMC Women's Health 1/2024 Go to the issue

Correction

Correction: Performance of Aptima-HPV in the cervical cancer screening program of Portugal: a cost-analysis

Research

A cross-sectional study observing the association of psychosocial stress and dietary intake with gut microbiota genera and alpha diversity among a young adult cohort of black and white women in Birmingham, Alabama

Research

Determinants of self-rated health among highly educated Ukrainian women refugees in Czechia: analysis based on cross-sectional study in 2022

Research

The relationship between resting metabolic rate and quality of life is moderated by age and body composition in women: a cross-sectional study

Research

A qualitative study on the adaptation of community programmes for the promotion of early detection and health-seeking of perinatal depression in Nepal

Case Report

Mullerian adenosarcoma of the uterus with MASO: a case report of cervical adenosarcoma in a young female that never had sexual behavior