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Endometriosis is a benign inflammatory condition characterised by the presence of endome-trial-like tissue outside the uterus. Patients with endometriosis often report pain symptoms such as dysmenorrhea and chronic pelvic pain. Medical and surgical treatments are not always effective due to limited understanding of the pain mechanisms. Studies on other chronic pain conditions indicate that chemokines, neurogenesis, and changes in the central nervous system, including GABAergic neurons, play a significant role in chronic pain development.

The purpose of the research presented in this thesis is to contribute to the understanding of the mechanisms that give rise to pain in women with endometriosis, and ultimately to improve treatment of the condition. Chemokines and their link to symptom severity were examined (Paper I). The endometrial innervation and its association with symptom severity and hormonal factors were studied (Paper II). The function of the GABAA receptor was evaluated (Paper III). Changes in pain symptoms after hysterectomy and the impact of patient characteristics and the extent of the surgery were explored (Paper IV).

The chemokines CCL2, CXCL8, and CXCL1 were assessed in blood samples and endome-trial samples from patients with endometriosis (n = 51) and controls (n = 22). Serum chemokine levels were measured using enzyme-linked immunosorbent assay (ELISA) kits, and the endometrial expression was quantified using immunohistochemistry and histoscore (Paper I). Serum hormone levels were measured and endometrial biopsies were assessed by immunohistochemistry for the density of nerve fibres. The endometrial innervation was compared between patients with endometriosis (n = 76) and controls (n = 24) (Paper II). Symptom severity was assessed using a visual analogue scale and the 30-item Endometriosis Health Profile (Papers I and II). For the assessment of GABAA-receptor function, patients with endometriosis (n = 15) and controls (n = 10) underwent a GABAA-receptor challenge test that measured changes in saccadic eye velocity after a GABAA-receptor agonist (Paper III). Data from patients with endometriosis who underwent hysterectomy in Sweden between 2010 and 2015, registered in the Swedish National Quality Register of Gynecological Surgery, were analysed (n = 137). Symptom severity before and 12 months after surgery, demographic data, and surgery details from the register were accessed, and supplemented by follow-up questionnaires with a median follow-up of 63 months (Paper IV).

The main findings were: that the endometrial expression of the chemokine CXCL1 was associated with pain intensity among patients with endometriosis, independent of whether the patient was receiving hormone treatment; patients with endometriosis expressed an increased innervation of the endometrium, and a higher endometrial innervation was associated with more severe pain in these patients; pelvic pain was reduced in most patients after hysterectomy, though one in four with severe pain symptoms before surgery still experienced these symptoms afterwards; notably, bilateral oophorectomy did not yield improved outcomes. Systemic changes were also observed; women with endometriosis had a decreased GABAA-receptor mediated response and an altered allopregnanolone/progesterone ratio, and this ratio was associated with the pain severity.

In conclusion, the intrauterine environment may play a role in the pain experienced by women with endometriosis, supported by the pain reduction seen after hysterectomy. However, the persistence of severe pain in some patients suggests that intrauterine factors would only bepart of the explanation. Alterations in allopregnanolone metabolism and GABAA-receptor function may also contribute to pain perception, warranting further research.