Hydration-induced Void-containing Hydrogels for Encapsulation and Sustained Release of Small Hydrophilic Molecules.

Efficient encapsulation and sustained release of small hydrophilic molecules from traditional hydrogel systems have been challenging due to the large mesh size of 3D networks and high water content. Furthermore, the encapsulated molecules are prone to early release from the hydrogel prior to use, resulting in a short shelf life of the formulation. Here, we present a hydration-induced void-containing hydrogel (HVH) based on hyperbranched polyglycerol-poly(propylene oxide)-hyperbranched polyglycerol (HPG-PPG-HPG) as a robust and efficient delivery system for small hydrophilic molecules. Specifically, after the HPG-PPG-HPG is incubated overnight at 4 °C in the drug solution, it is hydrated into a hydrogel containing micron-sized voids, which could encapsulate hydrophilic drugs and achieve 100% drug encapsulation efficiency. In addition, the voids are surrounded by a densely packed polymer matrix, which restricts drug transport to achieve sustained drug release. The hydrogel/drug formulation can be stored for several months without changing the drug encapsulation and release properties. HVH hydrogels are injectable due to shear thinning properties. In rats, a single injection of the HPG-PPG-HPG hydrogel containing 8 µg of tetrodotoxin (TTX) produced sciatic nerve block lasting up to 10 hours without any TTX-related systemic toxicity nor local toxicity to nerves and muscles.

Chronic pain in female breast cancer survivors - prevalence, characteristics and contributing factors: a cross-sectional pilot study.

BACKGROUND: While the global incidence of breast cancer is increasing, there is also an increase in the numbers of breast cancer survivors and in survival duration, as early detection programs are implemented, and treatments are optimized. Breast cancer survivors in several countries commonly struggle with a range of symptoms (fatigue, insomnia, depression) with 25-80% of survivors suffering from chronic pain. There is a paucity of literature reporting on breast cancer survivors in South Africa. In this pilot study we aimed to determine the prevalence of chronic pain in female breast cancer survivors attending the breast oncology clinic. METHODS: A cross-sectional survey was conducted of all breast cancer survivors attending the Groote Schuur Hospital Breast Unit during one month in 2019. 44 female breast cancer survivors (median age 60.5y) completed a sociodemographic questionnaire, the Brief Pain Inventory, Pain Catastrophizing Scale and measures for neuropathic pain (DN4), health related quality of life (HRQoL; EQ-5d-3 L), physical activity (IPAQ), depression and anxiety (PHQ4), and screening questions to evaluate sleep, happiness and perceived discrimination in the language of their choice. RESULTS: The prevalence of chronic pain (pain on most days for more than three months) was 59% (95%CI 44-72), a significantly higher number than the 18,3% prevalence of chronic pain reported by South African adults. 39% of the women were classified as having neuropathic pain. The median pain severity score was 3.75 (IQR = 2.75-5) and the median pain interference with function score was 4 (IQR = 2.9-5.4). The women were experiencing pain in a median of 2 different body sites (IQR = 1-3). The women with pain were more likely to be unemployed or receiving a disability grant, had significantly worse HRQoL, and significantly worse scores for risk of depression and anxiety. CONCLUSION: The results of this pilot study suggest that chronic pain may be a significant burden for South African breast cancer survivors. Routine screening for chronic pain in breast cancer survivors is recommended with a larger study indicated to explore this issue further.

Pain mechanisms in the transgender individual: a review.

Specific Aim: Provide an overview of the literature addressing major areas pertinent to pain in transgender persons and to identify areas of primary relevance for future research. Methods: A team of scholars that have previously published on different areas of related research met periodically though zoom conferencing between April 2021 and February 2023 to discuss relevant literature with the goal of providing an overview on the incidence, phenotype, and mechanisms of pain in transgender patients. Review sections were written after gathering information from systematic literature searches of published or publicly available electronic literature to be compiled for publication as part of a topical series on gender and pain in the Frontiers in Pain Research. Results: While transgender individuals represent a significant and increasingly visible component of the population, many researchers and clinicians are not well informed about the diversity in gender identity, physiology, hormonal status, and gender-affirming medical procedures utilized by transgender and other gender diverse patients. Transgender and cisgender people present with many of the same medical concerns, but research and treatment of these medical needs must reflect an appreciation of how differences in sex, gender, gender-affirming medical procedures, and minoritized status impact pain. Conclusions: While significant advances have occurred in our appreciation of pain, the review indicates the need to support more targeted research on treatment and prevention of pain in transgender individuals. This is particularly relevant both for gender-affirming medical interventions and related medical care. Of particular importance is the need for large long-term follow-up studies to ascertain best practices for such procedures. A multi-disciplinary approach with personalized interventions is of particular importance to move forward.

Drug Permeability: From the Blood-Brain Barrier to the Peripheral Nerve Barriers.

Drug delivery into the peripheral nerves and nerve roots has important implications for effective local anesthesia and treatment of peripheral neuropathies and chronic neuropathic pain. Similar to drugs that need to cross the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) to gain access to the central nervous system (CNS), drugs must cross the peripheral nerve barriers (PNB), formed by the perineurium and blood-nerve barrier (BNB) to modulate peripheral axons. Despite significant progress made to develop effective strategies to enhance BBB permeability in therapeutic drug design, efforts to enhance drug permeability and retention in peripheral nerves and nerve roots are relatively understudied. Guided by knowledge describing structural, molecular and functional similarities between restrictive neural barriers in the CNS and peripheral nervous system (PNS), we hypothesize that certain CNS drug delivery strategies are adaptable for peripheral nerve drug delivery. In this review, we describe the molecular, structural and functional similarities and differences between the BBB and PNB, summarize and compare existing CNS and peripheral nerve drug delivery strategies, and discuss the potential application of selected CNS delivery strategies to improve efficacious drug entry for peripheral nerve disorders.

Emulsion-induced polymersomes taming tetrodotoxin for prolonged duration local anesthesia.

Injectable local anesthetics that can provide a continuous nerve block approximating the duration of a pain state would be a life-changing solution for patients experiencing post-operative pain or chronic pain. Tetrodotoxin (TTX) is a site 1 sodium channel blocker that is extremely potent compared to clinically used local anesthetics. Challengingly, TTX doses are limited by its associated systemic toxicity, thus shortening the achievable duration of nerve blocks. Here, we explore emulsion-induced polymersomes (EIP) as a drug delivery system to safely use TTX for local anesthesia. By emulsifying hyperbranched polyglycerol-poly (propylene glycol)-hyperbranched polyglycerol (HPG-PPG-HPG) in TTX aqueous solution, HPG-PPG-HPG self-assembled into micrometer-sized polymersomes within seconds. The formed polymersomes have microscopically visible internal aqueous pockets that encapsulate TTX with an encapsulation efficiency of up to 94%. Moreover, the polymersomes are structurally stable, enabling sustained TTX release. In vivo, the freshly prepared EIP/TTX formulation can be directly injected and increased the tolerated dose of TTX in Sprague-Dawley rats to 11.5 µg without causing any TTX-related systemic toxicity. In the presence of the chemical penetration enhancer (CPE) sodium octyl sulfate (SOS), a single perineural injection of EIP/TTX/SOS formulation produced a reliable sciatic nerve block for 22 days with minimal local toxicity.

Optimizing and Accelerating the Development of Precision Pain Treatments for Chronic Pain: IMMPACT Review and Recommendations.

Large variability in the individual response to even the most-efficacious pain treatments is observed clinically, which has led to calls for a more personalized, tailored approach to treating patients with pain (ie, "precision pain medicine"). Precision pain medicine, currently an aspirational goal, would consist of empirically based algorithms that determine the optimal treatments, or treatment combinations, for specific patients (ie, targeting the right treatment, in the right dose, to the right patient, at the right time). Answering this question of "what works for whom" will certainly improve the clinical care of patients with pain. It may also support the success of novel drug development in pain, making it easier to identify novel treatments that work for certain patients and more accurately identify the magnitude of the treatment effect for those subgroups. Significant preliminary work has been done in this area, and analgesic trials are beginning to utilize precision pain medicine approaches such as stratified allocation on the basis of prespecified patient phenotypes using assessment methodologies such as quantitative sensory testing. Current major challenges within the field include: 1) identifying optimal measurement approaches to assessing patient characteristics that are most robustly and consistently predictive of inter-patient variation in specific analgesic treatment outcomes, 2) designing clinical trials that can identify treatment-by-phenotype interactions, and 3) selecting the most promising therapeutics to be tested in this way. This review surveys the current state of precision pain medicine, with a focus on drug treatments (which have been most-studied in a precision pain medicine context). It further presents a set of evidence-based recommendations for accelerating the application of precision pain methods in chronic pain research. PERSPECTIVE: Given the considerable variability in treatment outcomes for chronic pain, progress in precision pain treatment is critical for the field. An array of phenotypes and mechanisms contribute to chronic pain; this review summarizes current knowledge regarding which treatments are most effective for patients with specific biopsychosocial characteristics.

AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome.

PURPOSE: To provide a clinical framework for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. MATERIALS AND METHODS: A systematic review of the literature using the MEDLINE® database (search dates 1/1/83-7/22/09) was conducted to identify peer reviewed publications relevant to the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. Insufficient evidence-based data were retrieved regarding diagnosis and, therefore, this portion of the Guideline is based on Clinical Principles and Expert Opinion statements. The review yielded an evidence base of 86 treatment articles after application of inclusion/exclusion criteria. These publications were used to create the majority of the treatment portion of the Guideline. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate) or C (low). Additional treatment information is provided as Clinical Principles and Expert Opinion when insufficient evidence existed. See text and algorithm for definitions, and detailed diagnostic management, and treatment frameworks. RESULTS: The evidence-based guideline statements are provided for diagnosis and overall management of interstitial cystitis/bladder pain syndrome as well as for various treatments. The panel identified first through sixth line treatments as well as developed guideline statements on treatments that should not be offered. CONCLUSIONS: Interstitial cystitis/bladder pain syndrome is best identified and managed through use of a logical algorithm such as is presented in this Guideline. In the algorithm the panel identifies an overall management strategy for the interstitial cystitis/bladder pain syndrome patient. Diagnosis and treatment methodologies can be expected to change as the evidence base grows in the future.

Efficacy and Safety of Drug Combinations for Chronic Pelvic Pain: Protocol for a Systematic Review.

BACKGROUND: Chronic pelvic pain with various etiologies and mechanisms affects men and women and is a major challenge. Monotherapy is often unsuccessful for chronic pelvic pain, and combinations of different classes of medications are frequently prescribed, with the expectation of improved outcomes. Although a number of combination trials for chronic pelvic pain have been reported, we are not aware of any systematic reviews of the available evidence on combination drug therapy for chronic pelvic pain. OBJECTIVE: We have developed a protocol for a systematic review to evaluate available evidence of the efficacy and safety of drug combinations for chronic pelvic pain. METHODS: This systematic review will involve a detailed search of randomized controlled trials investigating drug combinations to treat chronic pelvic pain in adults. The databases searched will include the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE from their inception until the date the searches are run to identify relevant studies. The primary outcome will be pain relief measured using validated scoring tools. Secondary outcomes, where reported, will include the following: adverse events, serious adverse events, sexual function, quality of life, and depression and anxiety. Methodological quality of each included study will be assessed using the Cochrane Risk of Bias Tool. RESULTS: The systematic review defined by this protocol is expected to synthesize available good quality evidence on combination drug therapy in chronic pelvic pain, which may help guide future research and treatment choices for patients and their health care providers. CONCLUSIONS: This review will provide a clearer understanding of the efficacy and safety of combination pharmacological therapy for chronic pelvic pain. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020192231; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=192231. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/21909.

Pelvic pain and surgeries in women before interstitial cystitis/painful bladder syndrome.

OBJECTIVE: The objective of the study was to compare subjects with interstitial cystitis/painful bladder syndrome (IC/PBS) with controls on prior surgeries. STUDY DESIGN: IC/PBS subjects were compared with matched controls on surgeries and possible surgical indications prior to their index dates. RESULTS: Adjusted for demographic variables, logistic regression showed subjects exceeded controls in surgeries longer than 12 months and less than 1 month before the index date. However, addition of possible surgical indications showed chronic pelvic pain (CPP) to have a strong association with IC/PBS, whereas associations with surgeries were reduced to nonsignificance. CONCLUSION: Although women with IC/PBS were more likely to have experienced prior surgeries than controls, the apparent indications for surgeries, not the surgeries themselves, were stronger risk factors for IC/PBS. In particular, a prior history of CPP had a strong association with IC/PBS. Several features of study design, including extensive medical record review, suggest that prior CPP was not undiagnosed IC/PBS. Further investigation of CPP may yield insight into the pathogenesis of IC/PBS.

Women's sexual pain disorders.

INTRODUCTION: Women's sexual pain disorders include dyspareunia and vaginismus and there is need for state-of-the-art information in this area. AIM: To update the scientific evidence published in 2004, from the 2nd International Consultation on Sexual Medicine pertaining to the diagnosis and treatment of women's sexual pain disorders. METHODS: An expert committee, invited from six countries by the 3rd International Consultation, was comprised of eight researchers and clinicians from biological and social science disciplines, for the purpose of reviewing and grading the scientific evidence on nosology, etiology, diagnosis, and treatment of women's sexual pain disorders. MAIN OUTCOME MEASURE: Expert opinion was based on grading of evidence-based medical literature, extensive internal committee discussion, public presentation, and debate. Results. A comprehensive assessment of medical, sexual, and psychosocial history is recommended for diagnosis and management. Indications for general and focused pelvic genital examination are identified. Evidence-based recommendations for assessment of women's sexual pain disorders are reviewed. An evidence-based approach to management of these disorders is provided. CONCLUSIONS: Continued efforts are warranted to conduct research and scientific reporting on the optimal assessment and management of women's sexual pain disorders, including multidisciplinary approaches.

Vulvodynia.

Vulvodynia is a condition that occurs in 8-10% of women of all ages and is characterized by pain at the vulva that is present during sexual and/or non-sexual situations. Diagnosis is established through careful medical history and pelvic examination, including the cotton-swab test. The onset and maintenance of vulvodynia involves a complex interplay of peripheral and central pain mechanisms, pelvic floor muscle and autonomic dysfunction, anxiety, depression and childhood maltreatment as well as cognitive-affective, behavioural and interpersonal factors. Given the absence of empirically supported treatment guidelines, a stepwise approach of pelvic floor physical therapy and cognitive behavioural therapy as well as medical management is suggested, with surgery as the last option. Vulvodynia has a negative effect on the quality of life of women and their partners, and imposes a profound personal and societal economic burden. In addition, women with vulvodynia are more likely to report other chronic pain conditions, which further alters their quality of life. Future efforts should aim to increase girls', women's and healthcare professionals' education and awareness of vulvodynia, phenotype different subgroups of women based on biopsychosocial characteristics among more diverse samples, conduct longitudinal studies and improve clinical trial designs.

The IASP classification of chronic pain for ICD-11: chronic secondary visceral pain.

Chronic visceral pain is a frequent and disabling condition. Despite high prevalence and impact, chronic visceral pain is not represented in ICD-10 in a systematic manner. Chronic secondary visceral pain is chronic pain secondary to an underlying condition originating from internal organs of the head or neck region or of the thoracic, abdominal, or pelvic regions. It can be caused by persistent inflammation, by vascular mechanisms or by mechanical factors. The pain intensity is not necessarily fully correlated with the disease process, and the chronic visceral pain may persist beyond successful treatment of the underlying cause. This article describes how a new classification of chronic secondary visceral pain is intended to facilitate the diagnostic process and to enable the collection of accurate epidemiological data. Furthermore, it is hoped that the new classification will improve the tailoring of patient-centered pain treatment of chronic secondary visceral pain and stimulate research. Chronic secondary visceral pain should be distinguished from chronic primary visceral pain states that are considered diseases in their own right.

Sites of pain from interstitial cystitis/painful bladder syndrome.

PURPOSE: In interstitial cystitis/painful bladder syndrome multiple pain sites are common. We hypothesized that a careful and systematic description of the pain of interstitial cystitis/painful bladder syndrome might provide clues to its pathogenesis. MATERIALS AND METHODS: Women with 12 months or greater of interstitial cystitis/painful bladder syndrome symptoms underwent a medical record review and interview. Each completed a questionnaire that included views of the female body and described up to 5 interstitial cystitis/painful bladder syndrome pains, noting 40 descriptors for each. RESULTS: Two-thirds of the 226 patients reported multiple pains. Pain could be consolidated at 4 sites, including suprapubic, urethral, genital and nongenitourinary. Most descriptors were similar and little evidence indicated that 1 pain influenced pain at another site. Another 3 patterns were evident, including 1) a suprapubic > urethral > genital > nongenitourinary ranking in site distribution and at each site proportions that were solitary, the worst and the most frequent pains, and pains that responded to bladder events, 2) site specific allodynia, and 3) for urethral and genital pains a wider spectrum of sensations, including burning, stinging and sharp. Patients with urethral (38%) or genital (27%) pain did not differ from those without such pain in 95% of 44 important characteristics. CONCLUSIONS: Suprapubic prominence and changes in the voiding cycle are features consistent with but do not prove that the bladder is the pain generator in interstitial cystitis/painful bladder syndrome and the pain sites described by patients are referred from it. The patients with interstitial cystitis/painful bladder syndrome who might have been diagnosed with vulvodynia or urethral syndrome did not differ from others in important patient variables.

AAPT Diagnostic Criteria for Chronic Abdominal, Pelvic, and Urogenital Pain: Irritable Bowel Syndrome.

In conjunction with the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership with the U.S. Food and Drug Administration and the American Pain Society, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks-American Pain Society Pain Taxonomy (AAPT) initiative strove to develop the characteristics of a diagnostic system useful for clinical and research purposes across disciplines and types of chronic pain conditions. After the establishment of these characteristics, a working group of clinicians and clinical and basic scientists with expertise in abdominal, pelvic, and urogenital pain began generating core diagnostic criteria and defining the related extraintestinal somatic pain and other symptoms experienced by patients. Systematic diagnostic criteria for several common abdominal, pelvic, and urogenital pain conditions are in development. In this report, we present the proposed AAPT criteria for irritable bowel syndrome (IBS), the most common chronic, noncancer abdominal pain condition. A systematic review and synthesis was conducted to complement the Rome IV Diagnostic Criteria for IBS. Future efforts will subject these proposed AAPT criteria to systematic empirical evaluation of their feasibility, reliability, and validity. The AAPT IBS criteria are part of an evidence-based classification system that provides a consistent vocabulary regarding diagnostic criteria, common features, comorbidities, consequences, and putative mechanisms of the disorder. A similar approach is being applied to other chronic and often debilitating abdominal, pelvic, and urogenital pain conditions. PERSPECTIVE: The AAPT's goal is to develop an evidence-based taxonomy for chronic pain on the basis of a consistently applied multidimensional framework, and encourage experts to apply this taxonomy to specific chronic pain conditions. In this report, the taxonomy is applied to IBS, a chronic abdominal pain condition.

Research Design Characteristics of Published Pharmacologic Randomized Clinical Trials for Irritable Bowel Syndrome and Chronic Pelvic Pain Conditions: An ACTTION Systematic Review.

Chronic pain conditions occurring in the lower abdomen and pelvis are common, often challenging to manage, and can negatively affect health-related quality of life. Methodological challenges in designing randomized clinical trials (RCTs) for these conditions likely contributes to the limited number of available treatments. The goal of this systematic review of RCTs of pharmacologic treatments for irritable bowel syndrome and 3 common chronic pelvic pain conditions are to: 1) summarize the primary end points and entry criteria, and 2) evaluate the clarity of reporting of important methodological details. In total, 127 RCTs were included in the analysis. The most common inclusion criteria were a minimum pain duration (81%), fulfilling an established diagnostic criteria (61%), and reporting a minimum pain intensity (42%). Primary end points were identified for only 57% of trials. These end points, summarized in this article, were highly variable. The results of this systematic review can be used to inform future research to optimize the entry criteria and outcome measures for pain conditions occurring in the lower abdomen and pelvis, to increase transparency in reporting to allow for proper interpretation of RCT results for clinical and policy applications, and to facilitate the aggregation of data in meta-analyses. PERSPECTIVE: This article summarizes entry criteria and outcome measures and the clarity of reporting of these important design features in RCTs of irritable bowel syndrome and 3 common chronic pelvic pain conditions. These results can be used to improve design of future trials of these largely unaddressed pain conditions.

Visceral pain as a triggering factor for fibromyalgia symptoms in comorbid patients.

Fibromyalgia syndrome (FMS) is a central sensitization syndrome; however, peripheral pain sources potentially exacerbate its symptoms of chronic diffuse musculoskeletal pain and hyperalgesia. This prospective study evaluated visceral pain as a possible triggering factor for FMS pain and hyperalgesia in comorbid patients. Women with (1) FMS + irritable bowel syndrome (IBS); (2) FMS + primary dysmenorrhea (Dys); (3) FMS + Dys secondary to endometriosis (Endo); (4) FMS + colon diverticulosis (Div) were compared with FMS-only women, for fibromyalgia pain (number and intensity of episodes and analgesic consumption) over comparable periods and for somatic hyperalgesia (electrical and pressure pain thresholds) in painful (tender points) and control areas (trapezius, deltoid, quadriceps muscles, and overlying subcutis and skin). In comorbid subgroups, FMS symptoms were also reassessed after treatment of the visceral condition or no treatment. All comorbid groups vs FMS-only had significantly higher FMS pain (number/intensity of episodes and analgesic consumption) and hyperalgesia in deep somatic tissues (subcutis and muscle) at all sites (0.05 < P < 0.0001). Visceral pain (number of IBS days, painful menstrual cycles, and abdominal pain episodes from diverticulitis) correlated directly with all parameters of FMS pain and inversely with muscle pain thresholds at all sites (0.03 < P < 0.0001). Fibromyalgia syndrome pain and hyperalgesia in all tissues and all sites significantly decreased in patients after visceral comorbidity treatment (dietary for 6 months [IBS], hormonal for 6 months [dysmenorrhea], laser [endometriosis], and surgery [diverticulosis]) (0.05 < P < 0.0001) vs no change in untreated patients. Visceral pain enhances FMS symptoms, probably augmenting the level of central sensitization typical of the syndrome. Systematic assessment and treatment of visceral pain comorbidities should be a part of FMS management strategy.

Recommendations for Self-Report Outcome Measures in Vulvodynia Clinical Trials.

OBJECTIVES: Vulvodynia (idiopathic chronic vulvar pain) is a prevalent condition associated with significant and negative impacts in many areas of function. Despite the increased research interest in vulvodynia in recent years, recommendations for outcome measures for use in clinical trials are missing. The purpose of this paper, therefore, was to provide recommendations for outcome measures for vulvodynia clinical trials so that consistent measures are used across trials to facilitate between-study comparisons and the conduct of large multicenter trials, and to improve measurement of the multiple dimensions of vulvodynia. METHODS: Given that provoked vestibulodynia (PVD)-characterized by provoked pain localized to the vaginal opening-is the most common subtype of vulvodynia and the current main focus of clinical trials, this paper focused on recommended outcome measures in PVD clinical trials. The framework used to guide the selection of outcome measures was based on the one proposed by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). RESULTS: The IMMPACT framework provided a well-suited guideline for outcome measure recommendations in PVD clinical trials. However, given the provoked presentation of PVD and the significant impact it has on sexuality, modifications to some of the IMMPACT recommendations were made and specific additional measures were suggested. DISCUSSION: Measures that are specific to vulvovaginal pain are ideal for adoption in PVD clinical trials, and many such measures currently exist that allow the relevant IMMPACT domains to be captured.

Vulvodynia: a state-of-the-art consensus on definitions, diagnosis and management.

Vulvodynia is a chronic pain syndrome affecting up to 18% of the female population. Despite its high prevalence and associated distress, the etiology, diagnosis and clinical management of the disorder have not been clearly delineated. This "white paper" describes the findings and recommendations of a consensus conference panel based on a comprehensive review of the published literature on vulvodynia in addition to expert presentations on research findings and clinical management approaches. The consensus panel also identified key topics and issues forfurther research, including the role of inflammatory mechanisms and genetic factors and psychosexual contributors.