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PURPOSE:: This study compared lipid peroxidation values in nonobese and obese postmenopausal women before and after acute maximal aerobic exercise (AX).METHODS:: Blood samples were collected in nonobese (22.1 ± 0.9% body fat) and obese (40.8 ± 0.9% body fat) women (61–75 yr, N = 34) before and immediately after a maximal graded treadmill test. Lipid hydroperoxides (PEROX), cholesterol, and thiol profiles were measured. Oxygen consumption (V̇O2), respiratory exchange ratios (RER), and minute ventilation (V̇E) values were determined before and during exercise.RESULTS:: PEROX levels were not different between the nonobese and obese groups at baseline (2.4 vs 2.8 nmol·mL, respectively) or post-AX (2.8 vs 3.2 nmol·mL, respectively) (P > 0.05). When expressed as ΔPEROX (nmol·mL)/ΔV̇O2 (mL·kg·min), to account for different exercise durations, the obese group had a greater lipid peroxidation response compared with the nonobese group (0.13 vs 0.02 (nmol·mL)·mL·kg·min, respectively; P < 0.05). Regression analysis revealed that when baseline PEROX and body fat values were controlled, age, exercise intensity, and duration were significant contributors to the ΔPEROX/ΔV̇O2 after AX (R = 0.536 P < 0.05).CONCLUSION:: For a given oxidative challenge (exercise-associated oxygen utilization), older, obese women were at a greater risk for oxidative stress compared with nonobese counterparts. [ABSTRACT FROM AUTHOR]

VINCENT, H. K., J. W. MORGAN, and K. R. VINCENT. Obesity Exacerbates Oxidative Stress Levels after Acute Exercise. Med. Sci. Sports Exerc., Vol. 36, No. 5, pp. 772'''779, 2004. INTRODUCTION/PURPOSE:: This study compared oxidative stress levels and antioxidant capacity in nonobese and obese participants after acute resistance (RX) and aerobic exercise (AX). METHODS:: Blood samples were collected from 28 nonobese (mean = 20.8% body fat) and obese (mean = 35.0% body fat) participants pre- and immediately post-RX and AX. Lipid hydroperoxides (PEROX), malondialdehyde (TBARS) and total antioxidant status (TAS) were measured. Oxygen consumption (&OV0312;O2) and minute ventilation (&OV0312;E) values were determined during each exercise session. RESULTS:: In both groups, PEROX and TBARS were elevated post-RX and AX, with the greater elevations occurring in the obese group in each case (P < 0.05). In the obese, TBARS increased by 42% and 41% post-RX and AX, respectively, compared with 7.1% and 26.9% in the nonobese group. PEROX increased by 100% and 70% post-RX and AX, respectively, in the obese, and by 85% and 62% in the nonobese. TAS was 17% higher (P < 0.05) post-RX in the nonobese compared with the obese, whereas TAS values were not different post-AX. Peak and average &OV0312;E, and relative &OV0312;O2). rates were higher in the obese post-AX compared with the nonobese (P < 0.05) Correlations existed between the exercise-induced change in PEROX and body fat, vitamin C and A intake, peak oxygen consumption, and exercise ventilation rates in the obese group (r = 0.784'''0.776, P < 0.05). In both groups, the exercise-induced changes in PEROX were associated with vitamin C intake, exercise ventilation rates, &OV0312;O2peak, and plasma triglycerides (r = 0.669'''0.558, P < 0.05). CONCLUSION:: Lipid peroxidation is elevated in both RX and AX, and it is exacerbated in the obese. The mechanisms underlying this response in each exercise may be different but could involve plasma triglycerides, oxygen consumption, and antioxidant intake. [ABSTRACT FROM AUTHOR]

Abstract: Endometriosis, a common cause for chronic pelvic pain, significantly affects quality of life, fertility, and overall productivity of those affected. Therapeutic options remain limited, and collating evidence on treatment efficacy is complicated. One reason could be the heterogeneity of assessed outcomes in nonsurgical clinical trials, impeding meaningful result comparisons. This systematic literature review examines outcome domains and patient-reported outcome measures (PROMs) used in clinical trials. Through comprehensive search of Embase, MEDLINE, and CENTRAL up until July 2022, we screened 1286 records, of which 191 were included in our analyses. Methodological quality (GRADE criteria), information about publication, patient population, and intervention were assessed, and domains as well as PROMs were extracted and analyzed. In accordance with IMMPACT domain framework, the domain pain was assessed in almost all studies (98.4%), followed by adverse events (73.8%). By contrast, assessment of physical functioning (29.8%), improvement and satisfaction (14.1%), and emotional functioning (6.8%) occurred less frequently. Studies of a better methodological quality tended to use more different domains. Nevertheless, combinations of more than 2 domains were rare, failing to comprehensively capture the bio-psycho-social aspects of endometriosis-associated pain. The PROMs used showed an even broader heterogeneity across all studies. Our findings underscore the large heterogeneity of assessed domains and PROMs in clinical pain-related endometriosis trials. This highlights the urgent need for a standardized approach to both, assessed domains and high-quality PROMs ideally realized through development and implementation of a core outcome set, encompassing the most pivotal domains and PROMs for both, stakeholders and patients., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Abstract: A cross-sectional multinational collaborative study on women with endometriosis from Latin America and Spain uncovered high levels of painful symptomatology and high pain catastrophizing scores. Associations between pain perception/catastrophizing and race/ethnicity have been documented. This study was conducted to uncover factors moderating pelvic pain severity, including socioeconomic variables, self-identified race, and pain catastrophizing in women with endometriosis from Latin America and Spain, a population encompassing diverse racial and sociocultural contexts. Self-reported data on demographics, clinical history, Ob-Gyn history, pelvic pain intensity, and pain catastrophizing were collected with the Spanish World Endometriosis Research Foundation (WERF) Endometriosis Phenome Project (EPhect) Clinical Questionnaire (ECQ). Multiple logistic regression was conducted to analyze effects of self-identified race, demographic clusters (defined as countries with similar racial population distribution), socioeconomic factors, and pain catastrophizing on reporting severe vs moderate-mild levels of dysmenorrhea, dyspareunia, and pelvic pain. Self-identified race did not affect the likelihood of reporting severe pelvic pain; however, there were significant differences in reporting severe dysmenorrhea at worst among demographic clusters. Older age was associated with severe dyspareunia at worst and recent pelvic pain. Pain catastrophizing score was highly predictive of reporting most types of severe pelvic pain, regardless of race and demographic cluster. These results negate a role of racial categories as moderator of pain in women from Latin America and Spain and support integration of pain catastrophizing assessments and psychological interventions into the pain management plan to enhance therapeutic outcomes and QoL for patients with endometriosis., (Copyright © 2024 International Association for the Study of Pain.)

Competing Interests: Financial Disclosure: Katy Vincent reports money was paid to her institution from Reckitts, Gedeon Richter, and UKRI. Research funding was paid to her institution from NIHR, NIH and the EU IMI2 scheme. Emma Evans did not report any potential conflicts of interest.

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.)

Abstract: Postoperative pain management is still insufficient, leading to major deficits, including patient suffering, impaired surgical recovery, long-term opioid intake, and postsurgical chronic pain. Yet, identifying the best treatment options refers to a heterogeneous outcome assessment in clinical trials, not always reflecting relevant pain-related aspects after surgery and therefore hamper evidence synthesis. Establishing a core outcome set for perioperative pain management of acute pain after surgery may overcome such limitations. An international, stepwise consensus process on outcome domains ("what to measure") for pain management after surgery, eg, after total knee arthroplasty, sternotomy, breast surgery, and surgery related to endometriosis, was performed. The process, guided by a steering committee, involved 9 international stakeholder groups and patient representatives. The face-to-face meeting was prepared by systematic literature searches identifying common outcome domains for each of the 4 surgical procedures and included breakout group sessions, world-café formats, plenary panel discussions, and final voting. The panel finally suggested an overall core outcome set for perioperative pain management with 5 core outcome domains: physical function (for a condition-specific measurement), pain intensity at rest, pain intensity during activity, adverse events, and self-efficacy. Innovative aspects of this work were inclusion of the psychological domain self-efficacy, as well as the specific assessment of pain intensity during activity and physical function recommended to be assessed in a condition-specific manner. The IMI-PROMPT core outcome set seeks to improve assessing efficacy and effectiveness of perioperative pain management in any clinical and observational studies as well as in clinical practice., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Abstract: Endometriosis (ENDO) and interstitial cystitis/bladder pain syndrome (IC/BPS) are chronic pain conditions for which better treatments are urgently needed. Development of new therapies with proven clinical benefit has been slow. We have conducted a review of existing preclinical in vivo models for ENDO and IC/BPS in rodents, discussed to what extent they replicate the phenotype and pain experience of patients, as well as their relevance for translational research. In 1009 publications detailing ENDO models, 41% used autologous, 26% syngeneic, 18% xenograft, and 11% allogeneic tissue in transplantation models. Intraperitoneal injection of endometrial tissue was the subcategory with the highest construct validity score for translational research. From 1055 IC/BPS publications, most interventions were bladder centric (85%), followed by complex mechanisms (8%) and stress-induced models (7%). Within these categories, the most frequently used models were instillation of irritants (92%), autoimmune (43%), and water avoidance stress (39%), respectively. Notably, although pelvic pain is a hallmark of both conditions and a key endpoint for development of novel therapies, only a small proportion of the studies (models of ENDO: 0.5%-12% and models of IC/BPS: 20%-44%) examined endpoints associated with pain. Moreover, only 2% and 3% of publications using models of ENDO and IC/BPS investigated nonevoked pain endpoints. This analysis highlights the wide variety of models used, limiting reproducibility and translation of results. We recommend refining models so that they better reflect clinical reality, sharing protocols, and using standardized endpoints to improve reproducibility. We are addressing this in our project Innovative Medicines Initiative-PainCare/Translational Research in Pelvic Pain., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Metabotropic glutamate receptor 5 (mGluR5) is an excitatory G-protein-coupled receptor (GPCR) present in the spinal cord dorsal horn (SCDH) where it has a well-established role in pain. In addition to its traditional location on the cytoplasmic membrane, recent evidence shows that these receptors are present intracellularly on the nuclear membrane in the spinal cord dorsal horn and are implicated in neuropathic pain. Nuclear mGluR5 is a functional receptor that binds glutamate entering the cell through the neuronal glutamate transporter (GT) EAAT3 and activates transcription factor c-fos, whereas plasma membrane mGluR5 is responsible for c-jun activation. Here, we extend these findings to a model of inflammatory pain using complete Freund's adjuvant (CFA) and show that nuclear mGluR5 is also upregulated in the spinal cord dorsal horn following inflammation. We also show that pretreatment with an excitatory amino acid transporter (EAAT) inhibitor attenuates pain and decreases Fos, but not Jun, expression in complete Freund's adjuvant rats. In contrast, selective glial glutamate transporter inhibitors are pronociceptive and increase spinal glutamate concentrations. Additionally, we found that permeable mGluR5 antagonists are more effective at attenuating pain and Fos expression than nonpermeable group I mGluR antagonists. Taken together, these results suggest that under inflammatory conditions, intracellular mGluR5 is actively involved in the relay of nociceptive information in the spinal cord.

The combined oral contraceptive pill (COCP) has been implicated in the development of a number of chronic pain conditions. Modern COCP formulations produce a low endogenous estradiol, low progesterone environment similar to the early follicular phase of the natural menstrual cycle, with a variable effect on serum androgen levels. We used behavioural measures and functional magnetic resonance imaging to investigate the response to experimental thermal stimuli in healthy women, in both a natural and COCP-induced low endogenous estradiol state, to investigate whether alterations in central pain processing may underlie these observations in COCP users. Although COCP users overall did not require lower temperatures to obtain a fixed pain intensity, alterations in the brain response to these stimuli were observed. In a subgroup of COCP users with significantly reduced serum testosterone, however, lower temperatures were required. Region-of-interest analysis revealed that within key regions of the descending pain inhibitory system, activity in response to noxious stimulation varied with serum testosterone levels in both groups of women. Of particular interest, in COCP users, activity in the rostral ventromedial medulla increased with increasing testosterone and in those women with low testosterone, was significantly reduced compared to controls. These findings suggest that, in a low endogenous estradiol state, testosterone may be a key factor in modulating pain sensitivity via descending pathways. Specifically, failure to engage descending inhibition at the level of the rostral ventromedial medulla may be responsible for the reduction in temperature required by COCP users with low circulating testosterone., (Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Patients with chronic pain conditions demonstrate altered central processing of experimental noxious stimuli, dysfunction of the hypothalamic-pituitary-adrenal axis, and reduced quality of life. Dysmenorrhoea is not considered a chronic pain condition, but is associated with enhanced behavioural responses to experimental noxious stimuli. We used behavioural measures, functional magnetic resonance imaging, and serum steroid hormone levels to investigate the response to experimental thermal stimuli in otherwise healthy women, with and without dysmenorrhoea. Women with dysmenorrhoea reported increased pain to noxious stimulation of the arm and abdomen throughout the menstrual cycle; no menstrual cycle effect was observed in either group. During menstruation, deactivation of brain regions in response to noxious stimulation was observed in control women but not in women with dysmenorrhoea. Without background pain (ie, in nonmenstrual phases), activity in the entorhinal cortex appeared to mediate the increased responses in women with dysmenorrhoea. Mean cortisol was significantly lower in women with dysmenorrhoea and was negatively correlated with the duration of the symptom. Additionally, women with dysmenorrhoea reported significantly lower physical but not mental quality of life. Thus, many features of chronic pain conditions are also seen in women with dysmenorrhoea: specifically a reduction in quality of life, suppression of the hypothalamic-pituitary-adrenal axis, and alterations in the central processing of experimental noxious stimuli. These alterations persist when there is no background pain and occur in response to stimuli at a site distant from that of the clinical pain. These findings indicate the potential importance of early and adequate treatment of dysmenorrhoea., (Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Purpose of Review: Pelvic pain is a common complaint of women that is frequently poorly managed. This review considers the current understanding of the mechanisms of pain perception and the development of chronic pain in the context of three gynaecological pain conditions. Recent advances in the management of these conditions are then discussed., Recent Findings: Persistent pelvic pain is associated with central changes, reflected by alterations in psychology, brain structure and function, and dysfunction of the hypothalamic-pituitary-adrenal axis. The many similarities among the conditions support the notion that chronic pain should be treated as a symptom in its own right, however, obtaining a diagnosis remains important to patients. Few new treatments have been developed recently, however, older treatments are being subjected to more rigorous testing and improvements in phenotyping should lead to better design of clinical trials., Summary: Good quality, well designed clinical trials are urgently required to improve the treatment of pelvic pain in women. However, a variety of successful treatments exist and outcomes can be optimized by individualizing treatment strategies in the context of a multidisciplinary package.

Purpose: Our goal was to determine the effects resistance training on circulating IGF-I and on two of its major binding proteins, IGFBP-1 and IGFBP-3. Additional goals were to compare the time course of hormonal changes with the time course of strength changes and to determine the effect of training volume on the extent of hormonal changes., Methods: Thirty-one men and women (mean age = 37 +/- 7 yr) completed a 25-wk, 3 d x wk(-1) program in which they performed single-set resistance training (1-SET, N = 11), multiple-set resistance training (3-SET, N = 11), or no exercise (Control, N = 9). Before training, and after 13 and 25 wk of training, blood hormones were analyzed and strength was assessed as the sum of one-repetition maximum (1-RM) for leg extension and chest press exercises., Results: During the first 13 wk of resistance training, circulating IGF-I increased by approximately 20% in both the 1-SET and 3-SET groups (P = 0.041). No further increases occurred between 13 and 25 wk. In the 3-SET group, IGFBP-3 decreased 20% between 13 and 25 wk (P = 0.008). Training did not alter IGFBP-1. Increases in 1-RM strength occurred mainly during the first 13 wk of training and were significantly higher with 3-SET training compared to 1-SET., Conclusions: These findings indicate that increased circulating IGF-I may, at least in part, mediate increases in strength that result from resistance training.

The purpose of this study was to evaluate the effects of 9 d of immobilization and partial suspension on muscle function at the wrist. Twelve female subjects (19-27 yr) wore a cast suspended from the neck by a sling that immobilized muscles acting on the wrist. Atrophy, muscle damage indicators, isometric and isokinetic strength, reaction time, speed of movement, and fatigability were assessed. Forearm muscle cross-sectional area decreased by 4.1% following immobilization and suspension. There was no indication that significant muscle degeneration occurred during immobilization or when muscles resumed normal function. Isometric strength for flexion and extension decreased by 29.3 and 32.5%, respectively. Concentric strength decrements for flexion, extension, pronation, and supination ranged from 8.9-21.7% at 2.11 and 3.16 rad.s-1. Eccentric strength decrements at 2.11 rad.s-1 for the same movements ranged from 12.5-18.5%. Fatigability was unaffected. Greater relative strength losses compared to decreased muscle cross-sectional area may be the result of a decrease in contractile protein density or unidentified neural factors following immobilization and partial suspension. However, neuromuscular control of reaction time was not affected.

Collagraft (Zimmer and Collagen Corporation) consists of a mixture of porous beads composed of 60% hydroxyapatite and 40% tricalcium phosphate ceramic and fibrillar collagen. When mixed with autogenous bone marrow, it serves as an effective bone graft substitute. Since September 1986, this material has been used in a multiclinic prospective trial, randomized against cancellous iliac crest autografts in the treatment of long bone fractures. To date, 267 patients have entered this study with 128 patients receiving cancellous autograft and 139 patients receiving Collagraft. At 6- and 12-month follow-ups, Collagraft appears to function as well as autogenous graft when used in the treatment of acute long bone fractures.