BDNF and TrKB expression levels in patients with endometriosis and their associations with dysmenorrhoea

Abstract

Background Brain-derived neurotrophic factor (BDNF) is a known regulator of the development and maintenance of chronic pain in various chronic disorders. Together with its high-affinity tyrosine kinase type B (TrKB) receptor, BDNF is extensively expressed in the mammalian female reproductive system. However, BDNF and TrKB expression in different stages of endometriosis and the relationship between the expression of each in ectopic lesions and endometriosis pain remain unclear. Methods Sixty-two women who underwent laparoscopic surgery were enrolled in this study: forty-six diagnosed with ovarian endometrioma (study group) and sixteen diagnosed with ovarian benign tumours (control group). Samples from eutopic endometrium and ovarian endometriotic lesions were obtained at laparoscopic surgery. BDNF and TrKB messenger RNA (mRNA) and proteins levels in the eutopic and ectopic endometrium of both groups were measured by real-time PCR and immunohistochemical staining, respectively. Before the surgery the visual analogue scale (VAS) was used to measure dysmenorrhoea. Results BDNF and TrKB expression levels were higher in ovarian endometriotic lesions than in eutopic endometrium and normal endometrium (P < 0.05), and there was no cyclical change. Furthermore, their expression levels were higher in eutopic endometrium than in normal endometrium (P < 0.05), and BDNF and TrKB levels were higher in stage IV ovarian endometriotic lesions than in stage II and III lesions (P < 0.05), with their expression being non-significantly higher in stage III than in stage II (P > 0.05). Additionally, correlation coefficients for the association analysis between the mRNA expression of BDNF or TrKB in eutopic endometrium and the dysmenorrhoea VAS score were r = 0.52 and r = 0.56 for BDNF and TrKB, respectively (P < 0.05). The correlation coefficients for the associations between BDNF and TrKB in both the eutopic and ectopic endometrium were r = 0.82 and r = 0.66, respectively (P < 0.05). Conclusions BDNF and TrKB are closely related to dysmenorrhoea caused by endometriosis and may be important in the pathobiology or pathophysiology of endometriosis.

The Prescription of Chinese Herbal Medicine and Risk of Endometriosis in Women with Rheumatoid Arthritis: A Population-Based Cohort Study

“…33 Meanwhile, BDNF, together with its high-affinity tyrosine kinase type B (TrKB) receptor, has been linked to the onset of severe female reproductive disorders, including endometriosis. 34 Further, the present investigation pointed out the positive effects of Ye-Jiao-Teng and Chuan-Niu-Xi in preventing the onset of endometriosis. A murine model showed that an extract of Ye-Jiao-Teng could downregulate nitric oxide (NO) and pro-inflammatory cytokines, such as TNF-α and IL-1β, which are key mediators of inflammation.…”

“… 33 Meanwhile, BDNF, together with its high-affinity tyrosine kinase type B (TrKB) receptor, has been linked to the onset of severe female reproductive disorders, including endometriosis. 34 …”

Actualization of differential diagnosis of chronic pelvic pain syndrome in women of reproductive age

“…Згідно з теорією нейроангіогенезу, BDNF, як відомо, є трофічним як для нервів, так і для капілярів [13]. BDNF бере участь у шляхах болю не лише на центральному рівні, відіграючи ключову роль у центральній сенсибілізації при багатьох формах гіпералгезії, але також і на периферії після пошкодження нерва, модулюючи сенсорну нейротрансмісію у ноцицептивному шляху, тому відіграє важливу роль у перебігу ноцицептивного та нейропатичного болю [15,17]. Механізм нейрогенезу при ендометріозі залучає нейротрофіни, такі, як BDNF.…”

“…За даними останніх досліджень, виявлено підвищення концентрації BDNF у сироватці та плазмі крові у жінок з ендометріозом, асоційованим із тазовим болем і безпліддям, порівняно з контрольними групами [7,[13][14][15]18]. Рівень BDNF у крові пацієнток з ендометріозом позитивно корелює з клінічною стадією ендометріозу, тяжкістю СХТБ та ступенем дисменореї [7,17,19]. Також рівні BDNF у плазмі крові позитивно корелюють із показниками рівня тяжкості болю [14,18,19].…”

Development and Validation of a novelin vitrodiagnostic test for endometriosis

“…Another interesting biomarker, brain-derived neurotrophic factor (BDNF), has been found to be linked with several pathways that are disturbed in women with endometriosis. BDNF is a neurotrophin (26) with a high-affinity to neurotrophic tyrosine receptor kinase 2 (NTRK2) also known as Tropomyosin receptor kinase B (TrKB), and this ligand-receptor pair participates in some aspects of uterine physiology (27). BDNF and NTRK2 were more significantly expressed in the uterus of women with endometriosis compared to disease-free controls (28); BDNF has been found to be dysregulated and overexpressed in ectopic but not in eutopic endometrial tissue.…”