Translational Research in Pelvic Pain

QST of the dorsal of the foot and midline lower abdomen according to the German Neuropathic Pain Network Protocol.

Assessment of the abdominal wall specifically looking for muscle tenderness according to a standardised protocol (an enhanced Carnetts test as described by Scheltinga and Roumen 2017). Subjects will be categorised into muscle tenderness present or absent.

A standardised conditioned pain modulation (CPM) paradigm will be used to investigate the change in pressure pain threshold on the dorsum of the foot. An ischaemic stimulus to the contralateral arm will be used as the conditioned stimulus. The foot PPT will be measured before the conditioned stimulus and immediately after. The change will be reported as the (PPTbefore - PPTafter).

Saliva will be collected at home at the specified times allowing a daily AUC of salivary cortisol for each subject to be calculated. Collection times: waking; 30-45 minutes after waking; before lunch; before dinner; bedtime.

A saliva sample will be collected at rest immediately before the CPM paradigm described in outcome 3 and then again immediately after. The ischaemic pain stimulus used as the conditioning stimulus in this paradigm is the most noxious component of the physiological testing paradigms used in this study and therefore the most likely to generate a stress response. The change will be reported as Cortisol(before)-Cortisol(after).

Assessed over a 20 minute period at rest.

Assessed at rest immediately before the CPM paradigm described in outcome 3 and then again immediately after. The ischaemic pain stimulus used as the conditioning stimulus in this paradigm is the most noxious component of the physiological testing paradigms used in this study and therefore the most likely to generate a stress response. The change will be reported as HR(before) - HR(after).

Assessed over a 20 minute period at rest. Measured in mmHG.

Assessed at rest immediately before the CPM paradigm described in outcome 3 and then again immediately after. The ischaemic pain stimulus used as the conditioning stimulus in this paradigm is the most noxious component of the physiological testing paradigms used in this study and therefore the most likely to generate a stress response. The change will be reported as BP(before) - BP(after).

Assessed with standardised non-invasive bladder filling paradigm, measured as time to verbal reports of different sensations of bladder fullness (first sensation, first urge) and then need to void (maximum tolerance) after drinking 600 ml water. Subjects will be categorised into those with bladder sensitivity compared to published norms for reproductive age women and those with normal bladder sensation.

Assessed with standardised non-invasive bladder filling paradigm described in outcome 10. The volume of urine voided when maximum tolerance is reached will be measured in mls.

fMRI scan with response to punctate stimuli of midline lower abdomen.

Measured with the Pain Catastrophising Scale (Sullivan). Scores range from 0 - 52 with high scores representing higher levels of pain catastrophising. Although three sub scales exist they will not be assessed for the purposes of these main analyses.

Measured with the Hospital Anxiety and Depression Scale (HADS). Scores range from 0 - 21 for each of the two sub scales measuring anxiety and depression. The two sub scales will be summed as a unidimensional measure of psychological distress in initial analyses (0 - 42 with higher scores representing greater distress).

Discovery study of levels of all known metabolite in plasma using an established validated proprietary tool designed by Metabolon (https://www.metabolon.com).

Study measuring levels of proteins detected on two panels (inflammation and neurological) as designed by OLink (https://www.olink.com).

Discovery transcriptomic analysis of matched eutopic and ectopic endometrium from endometriosis and control women will be performed on a subgroup of participants. Both descriptive data and pathway analysis will be performed.

Assessed with the complex medical symptoms inventory (CMSI).

The CMSI contains a 41 item symptom screener, which an increasing score on adds up to a higher functional somatic burden (scores range from 0-41). Additionally, clusters of symptoms point to specific diagnoses for which the full diagnostic criteria questions are provided allowing the commonest overlapping pain conditions to be screened for:

Fibromyalgia temporomandibular disorders irritable bowel syndrome chronic tension type headache migraine chronic low back pain myalgic encephalitis/chronic fatigue syndrome interstitial cystitis/painful bladder syndrome endometriosis vulvodynia

Assessed with the Childhood Traumatic Events Scale (CTES). Scores range from 0 - 42 with higher scores representing more experience of early trauma. No sub scales will be derived.

Assessed with the Recent Traumatic Events Scale (RTES). Scores range from 0 - 42 with higher scores representing more experience of recent trauma. No sub scales will be derived.