Search

Introduction: Chronic pelvic pain affects up to 24% of women worldwide and for up to 55% of these there is no associated pathology. Despite this there are no established treatments in this cohort. This is a secondary analysis of a randomised-controlled trial (GaPP2) to explore if there are measures which enable us to predict treatment outcome., Methods: GaPP2 recruited women with chronic pelvic pain and no identified pathology and compared the response to gabapentin and placebo. This analysis used variables collected at baseline including validated questionnaires. Binary logistic regression was used to create models to explore whether baseline variables predicted treatment response. Treatment response was determined using 30% reduction in average pain intensity, 30% reduction in worst pain intensity and the Patient Global Impression of Change ('marked' or 'very marked' improvement) individually. We also explored whether baseline variables predicted the occurrence of side-effects (dizziness, visual disturbances and drowsiness)., Results: Using the Patient Global Impression of Change questionnaire, we found a significant binary logistic regression ( p = 0.029, explaining 31% of the variance), with those with lower worst pain intensity (odds ratio (OR) of 0.393, 95% CI [0.217, 0.712]), lower bladder symptom score (OR = 0.788, CI [0.628, 0.989]), and higher mental component quality of life score (OR = 0.911, CI [0.840, 0.988]), more likely to have 'marked' or 'very marked' improvement when treated with gabapentin. We could not identify predictors of experiencing side-effects to gabapentin. However, we did find predictors of these in the placebo group (binary logistic regression ( p = 0.009) and explained 33% of the variance). Worse mental health (OR = 1.247, CI [1.019, 1.525]) and lower baseline pain interference (OR = 0.687, CI [0.483, 0.978]) were associated with having side effects, whilst the use of hormones reduced the risk of experiencing side effects (OR = 0.239, CI [0.084, 0.676])., Discussion: Researchers and clinicians are increasingly aware of the importance of personalised medicine and treatment decisions being driven by knowledge of what treatments work for whom. Our data suggests an important role of the Patient Global Impression of Change in clinical trials as it may better reflect balance between symptoms reduction and side-effects and therefore be more useful in clinician-patients joint decision making., Competing Interests: KV, AH and SM are listed as co-inventors on a patent application (UK Patent App No. 2217921.2, International Patent App No. PCT/GB2023/053076) relating to the use of the NRG3 loci as a predictive test to determine efficacy of gabapentin for chronic pelvic pain treatment. AH’s institution has received honoraria for consultancy from Roche Diagnostics, Gesynta and Joii, and he has received lecture fees from Theramex. AH’s institution has received grant funding from Roche Diagnostics. KV’s institution has received honoraria for consultancy and lectures from Bayer Healthcare, Reckitt, AbbVie and Gedeon Richter., (Copyright © 2024 Coxon, Amer, Daniels, Doust, Mackenzie, Horne and Vincent.)

Objective: To quantify the variation, triggers and impact on quality of life of symptom flares in women with chronic pelvic pain (CPP)., Design: Cross-sectional questionnaire within the Translational Research in Pelvic Pain clinical cohort study., Setting: Women with CPP, with subgroups of women with endometriosis (EAP), interstitial cystitis/bladder pain syndrome (BPS), comorbid endometriosis and interstitial cystitis/bladder pain syndrome (EABP), and those with pelvic pain without endometriosis or interstitial cystitis/bladder pain syndrome (PP)., Population or Sample: A total of 100 participants., Methods: Descriptive and comparative analysis from flares questionnaire., Main Outcome Measures: The prevalence, characteristics and triggers of short, medium and long symptom flares in CPP., Results: We received 100 responses of 104 questionnaires sent. Seventy-six per cent of women with CPP have ever experienced symptom flares of at least one length (short, medium and/or long). Flares are associated with painful and non-painful symptoms. There is large variation for the frequency, duration, symptoms and triggers for flares. Over 60% of participants reported flares as stopping them from doing things they would usually do, >80% reported thinking about symptoms of flares and >80% reported flares being bothersome., Conclusions: Flares are prevalent and clinically very important in CPP. More research is needed to elucidate the mechanisms and characteristics underlying flares. Clinical practice should include an enquiry into flares with the aim of finding strategies to lessen their burden., (© 2024 The Author(s). BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Endometriosis-associated pain is burdensome to both the individual and wider society. However, current treatment leaves many with persisting pain. Here, we highlight how recent work considering endometriosis in the context of chronic pain has altered our understanding and how this has the potential to improve clinical care., Competing Interests: Declaration of interests K.V. declares fees paid to her institution for consultancy and lectures from Bayer Healthcare, Gedeon Richter, AbbVie, and Reckitts and grant funding from NIHR, NIH US, MRC, and EU IMI-2., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Femoral acetabular impingement syndrome (FAIS) is a cause of hip pain thought to be nociceptive, although pain phenotypes e.g., burning, pain attacks, prickling, numbness etc., are reported, mimicking neuropathic pain. Although no lesion to the somatosensory system is identified, neuropathic pain (NeP) may explain why nociceptive-focussed treatments are not always successful., Objective: To identify NeP in patients with FAIS and investigate if related to poorer outcomes., Design: A secondary analysis of the Femoral Acetabular Impingement Trial (FAIT). Outcome of interest: PainDETECT questionnaire; secondary outcomes of interest; International Hip Outcome Tool (iHOT33), Hospital Anxiety and Depression Scale (HADS) and VAS 'average pain over a month', at baseline and 8 months follow-up. Intervention (surgery or physiotherapy) were pooled., Results: 173 data sets at baseline; 123 at 8 months follow-up. Baseline painDETECT identified three groups: 69% nociceptive, 19% unclear and 12% neuropathic pain phenotypes. Baseline, median scores were higher for the neuropathic group compared to the nociceptive group demonstrating borderline anxiety (9.5(5.3 to 14.2), 5(3 to 8), higher normal values for depression (7.5(2.3 to 11.8), (4(2 to 9), higher average pain (7 (6 to 8), 5(4 to 6) and lower iHOT33 14.2(9 to 21.1), 38.4(26.2 to 55.7). Post treatment, there was a median change in the neuropathic score in both iHOT33 (40.8 (25 to 76.5) with a median difference of 24.13 (CI 95% 10.46 to 45.92) and average pain 4.5(1.5 to 7) with a median difference of 2 (CI 95% 1 to 5) but to a lesser amount than the nociceptive group, iHOT33 (64(38.2 to 86.6) with a median difference of 15.50 (CI 95% 6.41 to 21.82) and average pain 3(1 to 5.7) with a median difference of 1 (CI 95% 0.5 to 1)., Conclusion: NeP exists in symptomatic FAIS patients and is associated with increased average pain, and functional limitations. Nociceptive-targeted treatment improves hip function and pain but with less improvement in the NeP group when compared to the nociceptive group. Pain phenotyping before intervention may improve outcomes. CONTRIBUTION OF PAPER., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Chronic pelvic pain (CPP) in women with no obvious pelvic pathology has few evidence-based treatment options. Our recent multicenter randomized controlled trial (GaPP2) in women with CPP and no obvious pelvic pathology showed that gabapentin did not relieve pain overall and was associated with more side effects than placebo. We conducted an exploratory genome-wide association study using eligible GaPP2 participants aiming to identify genetic variants associated with gabapentin response. One genome-wide significant association with gabapentin analgesic response was identified, rs4442490, an intron variant located in Neuregulin 3 ( NRG3 ) ( p  = 2·11×10 -8 ; OR = 18·82 (95% CI 4·86-72·83). Analysis of a large sample of UK Biobank participants demonstrated phenome-wide significant brain imaging features of rs4442490, particularly implicating the orbitofrontal cortex. NRG3 is expressed predominantly in central nervous system tissues and plays a critical role in nervous system development, maintenance, and repair, suggesting a neurobiologically plausible role in gabapentin efficacy and potential for personalized analgesic treatment., Competing Interests: SCM, NR, KV, KTZ, AWH, and LHRW are listed as co-inventors on a patent application (UK Patent App No. 2217921.2, International Patent App No. PCT/GB2023/053076) relating to the use of the NRG3 loci presented herein as a predictive test to determine the efficacy of gabapentin for chronic pelvic pain treatment. AWH’s institution has received honoraria for consultancy from Roche Diagnostics, Gesynta, and Joii, and he has received lecture fees from Theramex. AWH and LHRW’s institution has received grant funding from Roche Diagnostics. KV reports grant funding to the Institution from Bayer AG and honoraria for consultancy paid to the Institution from Bayer AG, Abbvie, Reckitts, and Gedeon Richter. KTZ reports grant funding to the Institution from Bayer AG, Roche Diagnostics, MDNA Life Sciences Ltd, and Exeltis Ltd, and royalty payments from scientific collaboration with Bayer AG. The other authors declare no competing interests., (Crown Copyright © 2024 Published by Elsevier Inc.)

Abstract: Chronic pelvic pain (CPP), despite its high prevalence, is still relatively poorly understood mechanistically. This study, as part of the Translational Research in Pelvic Pain (TRiPP) project, has used a full quantitative sensory testing (QST) paradigm to profile n = 85 women with and without CPP (endometriosis or bladder pain specifically). We used the foot as a control site and abdomen as the test site. Across 5 diagnostically determined subgroups, we found features which are common across different aetiologies, eg, gain of function in pressure pain threshold (PPT) when assessing responses from the lower abdomen or pelvis (referred pain site). However, disease-specific phenotypes were also identified, eg, greater mechanical allodynia in endometriosis, despite there being large heterogeneities within diagnostic groups. The most common QST sensory phenotype was mechanical hyperalgesia (>50% across all the groups). A "healthy' sensory phenotype was seen in <7% of CPP participants. Specific QST measures correlated with sensory symptoms assessed by the painDETECT questionnaire (pressure-evoked pain [painDETECT] and PPT [QST] [ r = 0.47, P < 0.001]; mechanical hyperalgesia (painDETECT) and mechanical pain sensitivity [MPS from QST] [ r = 0.38, P = 0.009]). The data suggest that participants with CPP are sensitive to both deep tissue and cutaneous inputs, suggesting that central mechanisms may be important in this cohort. We also see phenotypes such as thermal hyperalgesia, which may be the result of peripheral mechanisms, such as irritable nociceptors. This highlights the importance of stratifying patients into clinically meaningful phenotypes, which may have implications for the development of better therapeutic strategies for CPP., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Purpose of Review: This review looks to overview advances in endometriosis-associated pain, both in understanding the pain mechanisms involved and increasing treatment options with well designed clinical trials and meta-analyses., Recent Findings: Our understanding of endometriosis-associated pain has progressed from a purely nociceptive model to an awareness that both neuropathic and nociplastic mechanisms can be present for some people with endometriosis. Clinical trials and meta-analyses have demonstrated efficacy of surgical treatments and hormonal therapies. It is notable that currently, the basic science and clinical trials are not cross-fertilising., Summary: Following growth in other areas of chronic pain, there have been significant advances in our understanding of endometriosis-associated pain. However, there remains lots to explore and we are currently a long way from our goal of timely personalized holistic multidisciplinary treatment for all sufferers of endometriosis-associated pain., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Chronic pelvic pain (CPP) is a common condition affecting up to 26.6% of women, with many suffering for several years before diagnosis and/or treatment. Its clinical presentation is varied and there are frequently comorbid conditions both within and outside the pelvis. We aim to explore whether specific subgroups of women with CPP report different clinical symptoms and differing impact of pain on their quality of life (QoL)., Methods: The study is part of the Translational Research in Pelvic Pain (TRiPP) project which is a cross-sectional observational cohort study. The study includes 769 female participants of reproductive age who completed an extensive set of questions derived from standardised WERF EPHect questionnaires. Within this population we defined a control group (reporting no pelvic pain, no bladder pain syndrome, and no endometriosis diagnosis, N  = 230) and four pain groups: endometriosis-associated pain (EAP, N  = 237), interstitial cystitis/bladder pain syndrome (BPS, N  = 72), comorbid endometriosis-associated pain and BPS (EABP, N  = 120), and pelvic pain only (PP, N  = 127)., Results: Clinical profiles of women with CPP (13-50 years old) show variability of clinical symptoms. The EAP and EABP groups scored higher than the PP group ( p  < 0.001) on the pain intensity scales for non-cyclical pelvic pain and higher than both the BPS and PP groups ( p  < 0.001) on the dysmenorrhoea scale. The EABP group also had significantly higher scores for dyspareunia ( p  < 0.001), even though more than 50% of sexually active participants in each pain group reported interrupting and/or avoiding sexual intercourse due to pain in the last 12 months. Scores for the QoL questionnaire (SF-36) reveal that CPP patients had significantly lower QoL across all SF-36 subscales ( p  < 0.001). Significant effects were also observed between the pain groups for pain interference with their work ( p  < 0.001) and daily lives ( p  < 0.001), with the EABP suffering more compared to the EAP and PP groups ( p  < 0.001)., Discussion: Our results demonstrate the negative impact that chronic pain has on CPP patients' QoL and reveal an increased negative impact of pain on the comorbid EABP group. Furthermore, it demonstrates the importance of dyspareunia in women with CPP. Overall, our results demonstrate the need for further exploration of interventions targeting QoL more broadly and suggest that novel approaches to classifying women with CPP are needed., Competing Interests: AWH: reports grant funding from the MRC, NIHR, CSO, Wellbeing of Women, Roche Diagnostics, Astra Zeneca, Ferring, Charles Wolfson Charitable Trust and Standard Life. His employer has received consultancy fees from Roche Diagnostics, AbbVie, Nordic Pharma and Ferring, outside the submitted work. In addition, AWH has a patent for a serum biomarker for endometriosis pending. AH: Employee of Bayer AG, Germany. EPZ: received financial support from Grunenthal and Mundipharma for research activities and advisory and lecture fees from Grünenthal, Novartis and Mundipharma. In addition, she receives scientific support from the German Research Foundation (DFG), the Federal Ministry of Education and Research (BMBF), the German Federal Joint Committee (G-BA) and the Innovative Medicines Initiative (IMI) 2 Joint Undertaking under grant agreement No 777500. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA All money went to the institution EMP.-Z is working for RDT: Ad board for BAYER, IASP task force on chronic pain classification. CMB: Research Grants from Bayer Healthcare, MDNA Life Sciences, Roche Diagnostics, European Commission, NIH His employer has received consulancy fees from Myovant and ObsEva for work outside of this project. FC: Consultant and/or investigator for Allergan (Abbvie), Astellas, Bayer, Ipsen and Recordati. SAM: has been an advisory board member for AbbVie and Roche and receives research funding from the National Institutes of Health, the US Department of Defense, the J Willard and Alice S Marriott Foundation, and AbbVie; none are related to the presented work; the J Willard and Alice S Marriott Foundation supported enrollment of and data collection from the A2A cohort in Boston from which TRiPP data were sampled. KTZ: reports grant funding from EU Horizon 2020, NIH US, Wellbeing of Women, Bayer AG, Roche Diagnostics, Evotec-Lab282, MDNA Life Sciences, outside the submitted work. JN: Employee and shareholder of Bayer AG, Germany. KV: declares research funding from Bayer Healthcare and UKRI and honoraria for consultancy and talks and associated travel expenses from Bayer Healthcare, Grunenthal GmBH, AbbVie and Eli Lilly. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest, (© 2023 Demetriou, Krassowski, Abreu Mendes, Garbutt, Vitonis, Wilkins, Coxon, Arendt-Nielsen, Aziz, Birch, Horne, Hoffman, Hummelshoj, Lunde, Meijlink, Perro, Rahmioglu, Terry, Pogatzki-Zahn, Sieberg, Treede, Becker, Cruz, Missmer, Zondervan, Nagel and Vincent.)

Background: Pain is one of the primary symptoms of endometriosis, a chronic inflammatory condition characterised by the presence of endometrial tissue outside the uterus. Endometriosis-associated pain is commonly considered as nociceptive in nature, but its clinical presentation suggests that it might have neuropathic-like properties in a subgroup of patients. Methods: This is a cross sectional study using an online survey. The survey was distributed by patient support websites. The survey was composed of validated questionnaires assessing pain symptoms, psychological measures and questions about number of surgeries. Main Results: We had 1,417 responses which met the inclusion criteria. Using standard painDETECT cut-off scores, we found that pain was classified as neuropathic in 40% of patients and as mixed neuropathic/nociceptive in a further 35%. In line with observations in other neuropathic conditions, the neuropathic subgroup reported higher pain intensities, greater psychological distress and cognitive impairment. Neuropathic pain was also more likely in those with more surgeries to the abdomen and a longer history of pain. As revealed by a cluster analysis, those with a neuropathic pain component could further be divided into two subgroups based on their sensory profile. Conclusions: The data presented here indicate that endometriosis-associated pain includes a neuropathic-like component in a substantial proportion of women. Although further investigation is required, our finding challenges the current conceptualisation of endometriosis-associated pain as nociceptive and advocates for a new perspective on this type of pain, which is so debilitating to a large number of women., Competing Interests: KW has received Consultancy fees from P&G Health, Germany. KV declares that she has received research funding from Bayer AG, Honoraria from Eli Lilly and Honoraria and Consultancy fees from Bayer AG, Grünenthal GmBH and AbbeVie. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Coxon, Wiech and Vincent.)

Although pain is one of the main symptoms women with endometriosis present with, there is poor correlation between symptom severity and disease burden and the underlying biological mechanisms by which pain arises are still only poorly understood. We briefly review the neurobiology of pain before considering mechanisms that may be specifically relevant in the context of endometriosis. The role of pelvic factors such as new nerve fibre growth, peritoneal fluid and inflammation is explored with a particular focus on studies where these factors have been associated with pain symptoms rather than just being compared between women with endometriosis and disease-free controls. We then consider the role of the central nervous system and associated systems, including the stress axis and psychological factors, in the modulation of pain. The potential for changes in these systems to be a cause and/or a consequence of the pain and how they might explain some of the known associations between endometriosis and other somatic symptoms is discussed. The chapter concludes by considering the implications of these mechanisms on treatment strategies for these women., (Copyright © 2018. Published by Elsevier Ltd.)