Search

Objective Histopathology is the criterion standard for evaluating cervical squamous intraepithelial neoplasia (dysplasia). In this pilot feasibility study, we examined whether a novel 3-dimensional imaging device using Gabor-domain optical coherence microscopy (GDOCM) could distinguish features of cervical dysplasia comparable with histopathology. Methods A prospective observational pilot study enrolled a small sample of women undergoing loop electrosurgical excision procedure for cervical squamous intraepithelial neoplasia. Fresh ex vivo specimens were imaged with the GDOCM device. Digital images were reviewed by a pathologist who was blinded to the histopathology results. Histopathologic features were then compared with the digital observations. Results Standard histologic features of cervical squamous epithelium and of squamous intraepithelial neoplasia could be observed in GDOCM images. Cervical epithelium, stroma, basement membrane, and squamous papilla could all be identified. Human papillomavirus effects, such as vacuolization and cellular density, were also observed. Conclusions A GDOCM imaging system has the potential to obtain histologic resolution images of the cervix in the evaluation of squamous intraepithelial neoplasia. This pilot study allowed for optimizing the imaging system and paved the way for a future diagnostic accuracy study. The development of this technology could streamline the evaluation of patients at risk for cervical neoplasia.

OBJECTIVE Couple interventions for chronic pain have been shown to more effectively reduce pain intensity for individuals with chronic pain (ICPs) than individual behavioral interventions or usual care. This systematic review identified randomized controlled trials of couple interventions to highlight strategies that could be incorporated into psychotherapy with ICPs and their romantic partners. METHODS The authors identified articles reporting randomized controlled trials of couple interventions for chronic pain. Three databases were searched (ie, PubMed, Embase, and PsycInfo), resulting in 18 studies and 22 articles. RESULTS Couple interventions resulted in statistically significant improvements in pain intensity compared with other conditions in 8% to 40% of the studies depending on the comparator group (i.e., control, individual intervention, another couple intervention), and in statistically significant improvements on a pain-related outcome compared with other conditions in 31% to 50% of the studies depending on the comparator group (ie, control, individual intervention, another couple intervention). Educating couples about pain was the most common strategy (83%). Jointly administered relaxation or meditation skills were included in nearly half of the interventions (48%). Many interventions taught cognitive-behavioral skills jointly to couples (39%) or to the ICP with partner encouragement (30%). Teaching couples how to request and provide assistance (30%), and encouraging partners to avoid reinforcing pain behaviors (39%), occurred frequently. ICPs and their partners were often asked to set goals (30%). DISCUSSION This review outlined strategies included in couple interventions for chronic pain that are derived from the cognitive-behavioral therapy, acceptance and commitment therapy, and operant behavioral traditions, but delivered relationally. Therapists working with ICPs and their partners may integrate these strategies into their practice to help couples who are managing chronic pain.

Localized provoked vulvodynia (LPV) is the most common cause of chronic dyspareunia in premenopausal women, characterized by pain with light touch to the vulvar vestibule surrounding the vaginal opening. The devastating impact of LPV includes sexual dysfunction, infertility, depression, and even suicide. Yet, its etiology is unclear. No effective medical therapy exists; surgical removal of the painful vestibule is the last resort. In LPV, the vestibule expresses a unique inflammatory profile with elevated levels of pro-nociceptive proinflammatory mediators prostaglandin E2 (PGE2) and interleukin-6 (IL-6), which are linked to lower mechanical sensitivity thresholds. Specialized pro-resolving mediators (SPMs), lipids produced endogenously within the body, hold promise as an LPV treatment by resolving inflammation without impairing host defense. Ten of 13 commercially available SPMs reduced IL-6 and PGE2 production by vulvar fibroblasts, administered either before or after inflammatory stimulation. Using a murine vulvar pain model, coupling proinflammatory mediator quantification with mechanical sensitivity threshold determination, topical treatment with the SPM, maresin 1, decreased sensitivity and suppressed PGE2 levels. Docosahexaenoic acid (DHA), a precursor of maresin 1, was also effective in reducing PGE2 in vulvar fibroblasts and rapidly restored mouse sensitivity thresholds. Overall, SPMs and their precursors may be a safe and efficacious for LPV. Perspective Vulvodynia, like many pain conditions, is difficult to treat because disease origins are incompletely understood. Here, we applied our knowledge of more recently discovered vulvodynia disease mechanisms to screen novel therapeutics. We identified several specialized pro-resolving mediators as likely potent and safe for treating LPV with potential for broader application.

Background Emergency departments (EDs) have the potential to promote critical public and preventive health interventions. Cervical cancer (CC) screening has been a cornerstone of preventive health efforts for decades. Approximately 20% of U.S. women are not adherent with CC screening guidelines—considerably below the U.S. Federal Government's target. ED patients are disproportionately nonadherent with CC screening guidelines. The ED, therefore, is an optimal setting to target women with an intervention that promotes CC screening. Objectives To assess the feasibility and potential efficacy of an intervention, grounded in behavioral change theory, to promote uptake of CC screening among ED patients. Methods Design: Randomized clinical trial pilot study; Patients: Women aged 21–65 years that were identified in the ED to be nonadherent with CC screening recommendations; Setting: Single center urban academic ED. Results Among enrolled participants, 355 (79%) were determined to be adherent with screening recommendations and 95 (21%) were determined to be either nonadherent or have uncertain adherence. Among the nonadherent/uncertain group, 47 were randomized to the control condition (referral only) and 48 were randomized to the intervention condition. Thirty-six percent of participants in the control condition received or scheduled screening during the follow-up period. In the intervention condition, 43% received or scheduled screening during the follow-up period—a 19% relative improvement over the control condition. Conclusion This pilot study demonstrates feasibility and preliminary efficacy of a behavioral intervention to increase uptake of CC screening among ED patients.

Chronic pelvic pain (CPP) in women is characterized by complex etiologies, psychosocial comorbidities, and treatment difficulties. Dysmenorrhea and the associated psychosocial and functional impairment beginning in adolescence may facilitate the transition into more debilitating CPP. This study describes dysmenorrhea history in a clinical sample of women with CPP and identifies predictors of dysmenorrhea catastrophizing (anxiously ruminating about dysmenorrhea symptoms) and functional impairment. From January-August 2020, we recruited 105 female patients (18+ years of age) with CPP receiving care through a tertiary center for chronic pelvic/vulvar pain. Patients completed a questionnaire that elicited dysmenorrhea information prior to the onset of their non-cyclical CPP. Questions included past dysmenorrhea symptoms and treatments, dysmenorrhea catastrophizing, and dysmenorrhea interference with activities of daily living. Multiple linear regression models identified predictors of dysmenorrhea catastrophizing and interference. On average, participants were 36 years of age and predominantly non-Hispanic white (82%). The majority (78%) experienced dysmenorrhea with each or most menstrual cycles, rated as moderate or greater intensity, within 5 years of menarche. Of these, 55% previously sought treatment. Over-the-counter pain medications, heating pad, and birth control pills/patch/ring were the most commonly reported dysmenorrhea treatments, and 10% of patients reported history of prescription opioids and 11% of marijuana use. Duration of dysmenorrhea within each menstrual period and dysmenorrhea intensity were most predictive of dysmenorrhea catastrophizing. Dysmenorrhea intensity and catastrophizing were predictive of dysmenorrhea interference, with catastrophizing mediating 62% (95% CI = 42%-83%) of the effect of dysmenorrhea intensity on interference. The majority of women in our sample reported dysmenorrhea prior to developing CPP, with some using opioids and marijuana for managing dysmenorrhea. The duration and intensity of dysmenorrhea were key predictors of dysmenorrhea catastrophizing, which in turn largely explained dysmenorrhea-associated functional impairment. These findings underscore the importance of early intervention for dysmenorrhea.

Chronic vulvar pain is alarmingly common in women of reproductive age and is often accompanied by psychological distress, sexual dysfunction, and a significant reduction in quality of life. Localized provoked vulvodynia (LPV) is associated with intense vulvar pain concentrated in the vulvar vestibule (area surrounding vaginal opening). To date, the origins of vulvodynia are poorly understood, and treatment for LPV manages pain symptoms, but does not resolve the root causes of disease. Until recently, no definitive disease mechanisms had been identified; our work indicates LPV has inflammatory origins, although additional studies are needed to understand LPV pain. Bradykinin signaling is one of the most potent inducers of inflammatory pain and is a candidate contributor to LPV. We report that bradykinin receptors are expressed at elevated levels in LPV patient versus healthy control vestibular fibroblasts, and patient vestibular fibroblasts produce elevated levels of proinflammatory mediators with bradykinin stimulation. Inhibiting expression of one or both bradykinin receptors significantly reduces proinflammatory mediator production. Finally, we determined that bradykinin activates nuclear factor (NF)κB signaling (a major inflammatory pathway), whereas inhibition of NFκB successfully ablates this response. These data suggest that therapeutic agents targeting bradykinin sensing and/or NFκB may represent new, more specific options for LPV therapy. Perspective There is an unmet need for the development of more effective vulvodynia therapies. As we explore the mechanisms by which human vulvar fibroblasts respond to proinflammatory/propain stimuli, we move closer to understanding the origins of chronic vulvar pain and identifying new therapeutic targets, knowledge that could significantly improve patient care.

Localised provoked vulvodynia (LPV) is a common, chronic, and disabling condition: patients experience profound pain and a diminished quality of life. The aetiologic origins of vulvodynia are poorly understood, yet recent evidence suggests a link to site-specific inflammatory responses. Fibroblasts isolated from the vestibule of LPV patients are sensitive to proinflammatory stimuli and copiously produce pain-associated proinflammatory mediators (IL-6 and PGE2). Although LPV is a multifactorial disorder, understanding vulvar inflammation and targeting the inflammatory response should lead to treatment advances, especially for patients exhibiting signs of inflammation. NFκB (already targeted clinically) or other inflammatory components may be suitable therapeutic targets. Tweetable abstract Vulvodynia is a poorly understood, prevalent, and serious women's health issue requiring better understanding to improve therapy.

Vulvodynia is a condition that affects approximately 8% to 12% of women during their lifetimes. Vulvar vestibulodynia (VVD), the most common form of this condition, is characterized by pain with touch at the vulvar vestibule and resulting entryway dyspareunia. Studies suggest a multifactorial etiology; hormonal effects, muscle dysfunction, personality, psychosocial factors, and inflammatory mediators may all play some role in the development of this condition. Both peripheral and central sensitization to pain have been implicated in the development of enhanced pain experienced by women with VVD. Recommendations for the treatment of this condition exist; however, treatments of this condition have not been well studied. Few prospective placebo-controlled trials exist, and many of those that do have failed to show clinically relevant efficacy associated with traditional therapies. New studies into the etiology of this condition, as well as potential new therapies, are emerging, but the optimal approach has yet to be defined. Proper vulvar hygiene is recommended, and traditional therapies such as topical medications and centrally acting oral medications may continue to play a role in treatment. Newer studies elucidating the effects of personality and cognitive factors as well as pelvic floor muscle dysfunction in the development of this condition lend support for the inclusion of cognitive behavioral therapy and physical therapy/surface electromyographic biofeedback in the treatment regimen. Surgery for this condition exists, with success rates of 60% to 90%; however, it is recommended only in cases that have failed to respond to traditional therapy.

Background Sexual dysfunction is common in women with vulvodynia. Objective The purpose of this study was (1) to evaluate whether extended-release gabapentin is more effective than placebo in improving sexual function in women with provoked vulvodynia and whether there is a relationship between treatment outcome and pelvic pain muscle severity that is evaluated by palpation with standardized applied pressure and (2) to evaluate whether sexual function in women with provoked vulvodynia would approach that of control subjects who report no vulvar pain either before or after treatment. Study Design As a secondary outcome in a multicenter double-blind, randomized crossover trial, sexual function that was measured by the Female Sexual Function Index was evaluated with gabapentin (1200–3000 mg/d) compared with placebo. Pain-free control subjects, matched by age and race, also completed Female Sexual Function Index for comparison. Results From August 2012 to January 2016, 230 women were screened at 3 academic institutions, and 89 women were assigned randomly to treatment. Gabapentin was more effective than placebo in improving overall sexual function (adjusted mean difference, 1.3; 95% confidence interval, 0.4–2.2; P=.008), which included desire (mean difference, 0.2; 95% confidence interval, 0.0–3.3; P=.04), arousal (mean difference, 0.3; 95% confidence interval, 0.1–0.5; P=.004), and satisfaction (mean difference, 0.3; 95% confidence interval, 0.04–0.5; P=.02); however, sexual function remained significantly lower than in 56 matched vulvodynia pain-free control subjects. There was a moderate treatment effect among participants with baseline pelvic muscle pain severity scores above the median on the full Female Sexual Function Index scale (mean difference, 1.6; 95% confidence interval, 0.3–2.8; P=.02) and arousal (mean difference, 0.3; 95% confidence interval, 0.1–0.6; P=.01) and pain domains (mean difference, 0.4; 95% confidence interval, 0.02–0.9; P=.04). Conclusion Gabapentin improved sexual function in this group of women with provoked vulvodynia, although overall sexual function remained lower than women without the disorder. The most statistically significant increase was in the arousal domain of the Female Sexual Function Index that suggested a central mechanism of response. Women with median algometer pain scores >5 improved sexual function overall, but the improvement was more frequent than the pain domain. We hypothesize that gabapentin may be effective as a pharmacologic treatment for those women with provoked vulvodynia and increased pelvic muscle pain on examination.

Fibroblast strains were derived from 2 regions of the lower genital tract of localized provoked vulvodynia (LPV) cases and pain-free controls. Sixteen strains were derived from 4 cases and 4 controls, age and race matched, after presampling mechanical pain threshold assessments. Strains were challenged with 6 separate stimuli: live yeast species (Candida albicans, Candida glabrata, Candida tropicalis, and Saccharomyces cerevisiae), yeast extract (zymosan), or inactive vehicle. Production of prostaglandin E2 (PGE2) and interleukin 6 (IL-6) were proinflammatory response measures. Highest IL-6 and PGE2 occurred with vestibular strains after C albicans, C glabrata, and zymosan challenges, resulting in the ability to significantly predict IL-6 and PGE2 production by genital tract location. After C albicans and C glabrata challenge of all 16 fibroblast strains, adjusting for dual sampling of subjects, PGE2 and IL-6 production significantly predicted the presampling pain threshold from the genital tract site of sampling. At the same location of pain assessment and fibroblast sampling, in situ immunohistochemical (IHC)(+) fibroblasts for IL-6 and Cox-2 were quantified microscopically. The correlation between IL-6 production and IL-6 IHC(+) was statistically significant; however, biological significance is unknown because of the small number of IHC(+) IL-6 fibroblasts identified. A low fibroblast IL-6 IHC(+) count may result from most IL-6 produced by fibroblasts existing in a secreted extracellular state. Enhanced, site-specific, innate immune responsiveness to yeast pathogens by fibroblasts may be an early step in LPV pathogenesis. Fibroblast strain testing may offer an attractive and objective marker of LPV pathology in women with vulvodynia of inflammatory origin.

Objective Our goal was to gain a better understanding of the inflammatory pathways affected during localized vulvodynia, a poorly understood, common, and debilitating condition characterized by chronic pain of the vulvar vestibule. Study Design In a control matched study, primary human fibroblast strains were generated from biopsies collected from localized provoked vulvodynia (LPV) cases and from age- and race-matched controls. We then examined intracellular mechanisms by which these fibroblasts recognize pathogenic Candida albicans ; >70% of vulvodynia patients report the occurrence of prior chronic Candida infections, which is accompanied by localized inflammation and elevated production of proinflammatory/pain-associated interleukin (IL)-6 and prostaglandin E2 (PGE 2 ). We focused on examining the signaling pathways involved in recognition of yeast components that are present and abundant during chronic infection. Results Dectin-1, a surface receptor that binds C albicans cell wall glucan, was significantly elevated in vestibular vs external vulvar cells (from areas without pain) in both cases and controls, while its abundance was highest in LPV cases. Blocking Dectin-1 signaling significantly reduced pain-associated IL-6 and PGE 2 production during the response to C albicans . Furthermore, LPV patient vestibular cells produced inflammatory mediators in response to low numbers of C albicans cells, while external vulvar fibroblasts were nonresponsive. Inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (proinflammatory transcription factor) nearly abrogated IL-6 and PGE 2 production induced by C albicans , in keeping with observations that Dectin-1 signals through the nuclear factor kappa-light-chain-enhancer of activated B cells pathway. Conclusion These findings implicate that a fibroblast-mediated proinflammatory response to C albicans contributes to the induction of pain in LPV cases. Targeting this response may be an ideal strategy for the development of new vulvodynia therapies.