Central pain processing in women with chronic pelvic pain syndrome

Chronic pelvic pain (CPP) is chronic or persistent pain perceived in structures related to the pelvis of either men or women. It is often associated with negative cognitive, behavioural, sexual, and emotional consequences as well as with symptoms suggestive of lower urinary tract, sexual, bowel, pelvic floor or gynaecological dysfunction. The UK annual prevalence of CPP is estimated at 3.8% and it is thought there are approximately one million women with CPP living in the UK.CPP is the most common cause for gynaecology referral accounting for 20% of all gynaecology consultations and 40% of diagnostic laparoscopies. In approximately 35% of cases there is no obvious pelvic pathology, leading to the diagnosis of Chronic Pelvic Pain Syndrome (CPPS). Despite CPP being associated with significant socio-economic cost, it still remains poorly understood, making clinical management challenging. The overarching objective of my MD thesis was to understand how CPPS is clinically managed in the UK, understand the mechanisms underpinning central pain processing and how this knowledge can influence future clinical practice. Specifically, I had the following aims: 1) Investigate the current clinical management trends for women with CPPS in the UK. 2) Determine if there are differences in central pain processing between women with CPPS and healthy female volunteers with no pelvic pain. 3) Investigate if existing clinical questionnaires can stratify women with CPPS into clinically meaningful groups. To achieve the first aim, I designed and distributed an online survey to UK clinicians managing chronic pelvic pain. A descriptive statistical analysis of the responses was carried out using an online survey tool. My online survey generated 148 responses. 45% of survey respondents indicated that they felt the management of women with CPP in the UK is ‘poor’ or ‘very poor’. 51% of clinicians prioritised ‘pain management’ above other aspects of care. Pelvic ultrasound and diagnostic laparoscopy were the most frequently performed investigations (97% and 78% respectively). The majority of clinicians (66%) discharged patients back to primary care without any further management plan or follow-up after negative findings at diagnostic laparoscopy. Of those clinicians who instigate post-operative treatment, hormonal therapies were the most commonly used (combined oral contraceptive pill - 84%, GnRH analogues - 69%, progestogens - 52%). The survey results indicate that CPP is managed predominantly by obstetricians and gynaecologists with relatively low case load, suggesting that majority are not ‘specialists’ in the field. There is surprisingly high level of dissatisfaction amongst the clinicians about the care they provide. The majority of women are referred back to community care following ‘negative’ finding at diagnostic laparoscopy, often without treatment or follow-up plans. Survey participants reported lack of seamless referral pathways and lack of multi-disciplinary approach as main barriers in delivering quality care to women with pelvic pain. This highlights an urgent need for research, education and improved clinical guidance to advance the management of this common but challenging gynaecological problem. To address the second aim, I performed a case-controlled study comprising two groups of participants, women with CPPS and healthy female volunteers with no pelvic pain. Women with CPPS and healthy volunteers meeting the inclusion criteria completed validated measures of pain and psychological state, and provided a blood sample for serum estrogen and progesterone levels. Subsequently, all participants underwent a functional MRI (fMRI) scan of their brain. The scan session included an acquisition of structural images and event-related task fMRI with variable interval design, during which participants received punctate stimuli over the suprapubic area of the abdomen using 300-gramm Von Frey filament. The MRI data were analysed using FMRIB’s Software Library (FSL). Standard data pre-processing (brain extraction, registration, B0 field unwarping and motion correction) was carried out. FSL FEAT was used for the first and higher-level analyses using mixed effects methods (Z score threshold = 3.1, cluster corrected regions considered to be significant at P<0.05). A sub-group of healthy volunteers (n=13) was matched with women with CPPS (n=13) for their age (+/- 5 years) and hormonal status (method of contraception or the stage of menstrual cycle). This approach allowed further analyses controlling for hormonal state, a well-known factor influencing pain modulation. I investigated the hypothesised differences in central pain processing between women with CPPS and healthy female volunteers in two ways: 1) Base analysis: 42 women with CPPS compared with 15 healthy volunteers. This approach maximised sample size and statistical power but did not control for hormonal state differences between the groups. 2) Matched analysis: 13 ‘hormonally matched’ women with CPPS compared with 13 healthy volunteers. This approach controlled for the hormonal state, but smaller cohort had reduced power to detect fMRI differences in brain activity between the analysed groups. In the ‘base analysis’, there was no difference (P=0.46) in the age between healthy volunteers (median=27, range: 23-35) and women with CPPS (median=26, range: 19-50). As predicted, women with CPPS experienced significantly higher (P