Could relationship-based learnt beliefs and expectations contribute to physiological vulnerability of chronic pain? Making a case to consider attachment in pain research.

Pain is an interpersonal and inherently social experience. Pain perception and administration of medical treatment all occur in a particular environmental and social context. Early environmental influences, and early learning experiences and interactions, condition the body's response to different threats (like pain), ultimately shaping the underlying neurophysiology. These early interactions and experiences also determine what situations are perceived as threatening, as well as our belief in our own ability to self-manage, and our belief in others to offer support, during perceived threats. These beliefs intrinsically drive the combination of behaviours that emerge in response to perceived threats, including pain. Such behaviours can be categorised into attachment styles. In this interdisciplinary review, we synthesise and summarise evidence from the neurobiological, psychobiological, psychosocial and psychobehavioural fields, to describe how these beliefs are embedded in the brain's prediction models to generate a series of expectations/perceptions around the level of safety/threat in different contexts. As such, these beliefs may predict how one experiences, and responds to, pain; with potentially significant implications for the development and management of chronic pain. Little attention has been directed to the effect of adult attachment style on pain in research studies and in the clinical setting. Using interdisciplinary evidence, we argue why we think this interaction merits further consideration and research. PERSPECTIVE: This review explores the influence of attachment styles on pain perception, suggesting a link between social connections and chronic pain development. It aligns with recent calls to emphasise the social context in pain research and advocates for increased focus on adult attachment styles in research and clinical practice.

Correction: Could the ketogenic diet induce a shift in thyroid function and support a metabolic advantage in healthy participants? A pilot randomized-controlled-crossover trial.

[This corrects the article DOI: 10.1371/journal.pone.0269440.].

The complexities of the sleep-pain relationship in adolescents: A critical review.

Chronic pain is a common and disabling condition in adolescents. Disturbed sleep is associated with many detrimental effects in adolescents with acute and chronic pain. While sleep and pain are known to share a reciprocal relationship, the sleep-pain relationship in adolescence warrants further contextualization within normally occurring maturation of several biopsychological processes. Since sleep and pain disorders begin to emerge in early adolescence and are often comorbid, there is a need for a comprehensive picture of their interrelation especially related to temporal relationships and mechanistic drivers. While existing reviews provide a solid foundation for the interaction between disturbed sleep and pain in youth, we will extend this review by highlighting current methodological challenges for both sleep and pain assessments, exploring the recent evidence for directionality in the sleep-pain relationship, reviewing potential mechanisms and factors underlying the relationship, and providing direction for future investigations. We will also highlight the potential role of digital technologies in advancing the understanding of the sleep and pain relationship. Ultimately, we anticipate this information will facilitate further research and inform the management of pain and poor sleep, which will ultimately improve the quality of life in adolescents and reduce the risk of pain persisting into adulthood.

Moderate, Little, or No Improvements in Neurobehavioral Symptoms among Individuals with Long COVID: A 34-Country Retrospective Study.

(1) Background: Some people with COVID-19 develop a series of symptoms that last for several months after infection, known as Long COVID. Although these symptoms interfere with people's daily functioning and quality of life, few studies have focused on neurobehavioral symptoms and the risk factors associated with their development; (2) Methods: 1001 adults from 34 countries who had previously tested positive for COVID-19 completed the Neurobehavioral Symptom Inventory reporting the symptoms before their COVID-19 diagnosis, during the COVID-19 infection, and currently; (3) Results: Participants reported large-sized increases before vs. during COVID-19 in all domains. Participants reported a medium-sized improvement (during COVID-19 vs. now) in somatic symptoms, a small-sized improvement in affective symptoms, and very minor/no improvement in cognitive symptoms. The risk factors for increased neurobehavioral symptoms were: being female/trans, unemployed, younger age, low education, having another chronic health condition, greater COVID-19 severity, greater number of days since the COVID-19 diagnosis, not having received oxygen therapy, and having been hospitalized. Additionally, participants from North America, Europe, and Central Asia reported higher levels of symptoms across all domains relative to Latin America and Sub-Saharan Africa; (4) Conclusions: The results highlight the importance of evaluating and treating neurobehavioral symptoms after COVID-19, especially targeting the higher-risk groups identified. General rehabilitation strategies and evidence-based cognitive rehabilitation are needed in both the acute and Long COVID phases.

An international study of post-COVID sleep health.

OBJECTIVES: COVID-19 has infected millions of people worldwide, with growing evidence that individuals with a history of infection may continue to show persistent post-COVID symptoms (long COVID). The aim of this study was to investigate sleep health in an international sample of individuals who reported previously testing positive for COVID-19. DESIGN: Cross-sectional. SETTING: Online survey distributed online between March and June 2021. PARTICIPANTS: A total of 1001 individuals who reported a positive diagnosis of COVID-19 across different geographical regions, including North and South America, Sub-Saharan Africa, and Europe. MEASUREMENTS: Self-reported sleep health, using the Regulatory Satisfaction Alertness Timing Efficiency Duration scale, as recalled before a COVID-19 diagnosis and also reported currently. RESULTS: Individuals reported worse overall current sleep health, with lower ratings across the 6 dimensions of sleep health (sleep regularity, satisfaction, alertness, timing, efficiency, and duration) compared to their ratings as recalled before COVID-19 infection. Greater severity of COVID-19 symptoms was the strongest predictor of poor current sleep health (P < .001), independent of demographics, presence of a pre-existing chronic health condition, and time since infection. Poor current sleep health was associated with poorer current quality of life (P < .001). CONCLUSIONS: Poor current sleep health is evident in individuals with a history of COVID-19, particularly those with more severe symptoms at the time of their COVID-19 infection and is associated with a poorer quality of life. Clinicians and researchers should assess sleep health in COVID-19 patients and investigate long-term associations with their mental and physical health, as well as potential benefits of improving sleep in this population.

Could the ketogenic diet induce a shift in thyroid function and support a metabolic advantage in healthy participants? A pilot randomized-controlled-crossover trial.

BACKGROUND: The ketogenic diet (KD) has been shown to result in body mass loss in people with disease as well as healthy people, yet the effect of the KD on thyroid function and metabolism are unknown. OBJECTIVE: We aimed to determine the effects of a KD, compared with an isocaloric high-carbohydrate low-fat (HCLF) diet, on resting metabolic rate and thyroid function in healthy individuals. DESIGN: Eleven healthy, normal-weight participants (mean(SD) age: 30(9) years) completed this randomized crossover-controlled study. For a minimum of three weeks on each, participants followed two isocaloric diets: a HCLF diet (55%carbohydrate, 20%fat, 25%protein) and a KD (15%carbohydrate, 60%fat, 25% protein), with a one-week washout period in-between. Importantly, while on the KD, the participants were required to remain in a state of nutritional ketosis for three consecutive weeks. Crossover analyses and linear mixed models were used to assess effect of diet on body mass, thyroid function and resting metabolic rate. RESULTS: Both dietary interventions resulted in significant body mass loss (p<0.05) however three weeks of sustained ketosis (KD) resulted in a greater loss of body mass (mean (95%CI): -2.9 (-3.5, -2.4) kg) than did three weeks on the HCLF diet (-0.4 (-1.0, 0.1) kg, p < 0.0001). Compared to pre-diet levels, the change in plasma T3 concentration was significantly different between the two diets (p = 0.003), such that plasma T3 concentration was significantly lower following the KD diet (4.1 (3.8, 4.4) pmol/L, p<0.0001) but not different following the HCLF diet (4.8 (4.5, 5.2) pmol/L, p = 0.171. There was a significant increase in T4 concentration from pre-diet levels following the KD diet (19.3 (17.8, 20.9) pmol/L, p < 0.0001), but not following the HCLF diet (17.3 (15.7, 18.8) pmol.L, p = 0.28). The magnitude of change in plasma T4 concentration was not different between the two diets (p = 0.4). There was no effect of diet on plasma thyroid stimulating hormone concentration (p = 0.27). There was a significantly greater T3:T4 ratio following the HCLF diet (0.41 (0.27, 0.55), p < 0.0001) compared to pre-diet levels but not following the KD diet (0.25 (0.12, 0.39), p = 0.80). CONCLUSIONS: Although the diets were isocaloric and physical activity and resting metabolic rate remained constant, the participants lost more mass after the KD than after the HCLF diet. The observed significant changes in triiodothyronine concentration suggest that unknown metabolic changes occur in nutritional ketosis, changes that warrant further investigation. TRIAL REGISTRATION: Pan African Clinical Trial Registry: PACTR201707002406306 URL: https://pactr.samrc.ac.za/.

Network Analysis of Neurobehavioral Symptom Patterns in an International Sample of Spanish-Speakers with a History of COVID-19 and Controls.

(1) Background: Psychometric network analysis provides a novel statistical approach allowing researchers to model clusters of related symptoms as a dynamic system. This study applied network analysis to investigate the patterns of somatic, cognitive, and affective neurobehavioral symptoms in an international sample of Spanish-speaking individuals with a history of COVID-19 positivity and non-COVID controls; (2) methods: the sample (n = 1093) included 650 adults from 26 countries who reported having previously tested positive for COVID-19 (COVID+) through a viral and/or antigen test (average of 147 days since diagnosis). The control group (COVID-) was comprised of 443 adults from 20 countries who had completed the survey prior to the COVID-19 pandemic; (3) results: relative to the COVID- network, the COVID+ network was very well-connected, such that each neurobehavioral symptom was positively connected to the network. The organize-to-headache and dizzy-to-balance connections in the COVID+ network were stronger than in the COVID- network. The hearing, numbness, and tense symptoms were more central to the COVID+ network with the latter connected to the sleep, fatigue, and frustrated symptoms. The COVID- network was largely disjointed, with most of the somatosensory symptoms forming their own cluster with no connections to other symptom groups and fatigue not being connected to any other symptom. The cognitive and affective symptoms in the COVID- network were also largely connected to symptoms from within their own groups; (4) conclusions: These findings suggest that many of the long-term neurobehavioral symptoms of COVID-19 form a discernable network and that headaches, frustration, hearing problems, forgetfulness, and tension are the most central symptoms. Cognitive and behavioral rehabilitation strategies targeting these central symptom network features may hold promise to help fracture the lingering symptom network of COVID-19.

Why It Is Important to Consider the Effects of Analgesics on Sleep: A Critical Review.

We review the known physiological mechanisms underpinning all of pain processing, sleep regulation, and pharmacology of analgesics prescribed for chronic pain. In particular, we describe how commonly prescribed analgesics act in sleep-wake neural pathways, with potential unintended impact on sleep and/or wake function. Sleep disruption, whether pain- or drug-induced, negatively impacts quality of life, mental and physical health. In the context of chronic pain, poor sleep quality heightens pain sensitivity and may affect analgesic function, potentially resulting in further analgesic need. Clinicians already have to consider factors including efficacy, abuse potential, and likely side effects when making analgesic prescribing choices. We propose that analgesic-related sleep disruption should also be considered. The neurochemical mechanisms underlying the reciprocal relationship between pain and sleep are poorly understood, and studies investigating sleep in those with specific chronic pain conditions (including those with comorbidities) are lacking. We emphasize the importance of further work to clarify the effects (intended and unintended) of each analgesic class to inform personalized treatment decisions in patients with chronic pain. © 2021 American Physiological Society. Compr Physiol 11:1-31, 2021.

The COVID-19 Lockdown and Changes in Routine-Oriented Lifestyle Behaviors and Symptoms of Depression, Anxiety, and Insomnia in South Africa.

BACKGROUND: The authors assessed the impact of lockdown in response to the COVID-19 pandemic on routine-oriented lifestyle behaviors and symptoms of depression, anxiety, and insomnia in South Africans. METHODS: In this observational study, 1048 adults (median age = 27 y; n = 767 females; n = 473 students) responded to an online survey on work, exercise, screen, alcohol, caffeine and sleep behaviors, depression, anxiety, and insomnia before and during lockdown. Comparisons were made between males and females, and students and nonstudents. RESULTS: During lockdown, males reported larger reductions in higher intensity exercise and alcohol use than females, while depressive symptoms increased more among females, more of whom also reported poorer sleep quality. Students demonstrated larger delays in work and sleep timing, greater increases in sitting, screen, sleep duration, napping, depression and insomnia and larger decreases in work hours, exercise time, and sleep regularity compared with nonstudents. CONCLUSIONS: Students experienced more changes in their routine-oriented behaviors than nonstudents, coupled with larger increases in depression and insomnia. The dramatic change in their work and sleep timing suggests habitual routines that are at odds with their chronotype, with their sleep changes during lockdown likely reflecting "catch-up" sleep in response to accumulated sleep debt under usual routines.

Working nights and lower leisure-time physical activity associate with chronic pain in Southern African long-distance truck drivers: A cross-sectional study.

BACKGROUND: In South Africa, the trucking industry employs over 70,000 people and the prevalence of chronic pain in this occupational group was reported at 10%. We investigated factors associated with chronic pain in truck drivers including mental health, physical activity, and sleep, as no study has done so. METHODS: Southern African male, long-distance truck drivers were recruited at truck stops in Gauteng and Free State Provinces, South Africa (n = 614). Chronic pain was defined as pain present for at least the last three months. Depressive symptoms were assessed with the Patient Health Questionnaire-9, post-traumatic stress disorder with the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), exposure to traumatic events with the Life Events Checklist-5 (LEC-5) and daytime sleepiness with the Epworth Sleepiness Scale. Sleep quality was measured on a four-point Likert scale. Leisure-time physical activity was measured using the Godin-Shephard leisure-time physical activity questionnaire. Associations between these factors, demographic factors and chronic pain were investigated. RESULTS: Multivariate analysis showed that working ≥ 2 nights/week (OR = 2.68, 95% CI = 1.55-4.68) was associated with chronic pain and physical activity was protective (OR = 0.97, 95% CI 0.95-0.98). In an exploratory analysis, greater depressive symptoms (p = 0.004), daytime sleepiness (p = 0.01) and worse sleep quality (p = 0.001) was associated with working ≥ 2 nights/week. Lower leisure-time physical activity was associated with worse sleep quality (p = 0.006), but not daytime sleepiness or depressive symptoms (p>0.05). CONCLUSIONS: There is a clear relationship between working nights and activity levels, and chronic pain, sleep quality, and depression in truck drivers.

Three consecutive weeks of nutritional ketosis has no effect on cognitive function, sleep, and mood compared with a high-carbohydrate, low-fat diet in healthy individuals: a randomized, crossover, controlled trial.

BACKGROUND: The high-fat ketogenic diet (KD) has become an increasingly popular diet not only in overweight/obese populations, or those with clinical conditions, but also in healthy non-overweight populations. OBJECTIVE: Because there are concerns about the association between high-fat diets and cognitive decline, this study aimed to determine the effects of a KD compared with an isocaloric high-carbohydrate, low-fat (HCLF) diet on cognitive function, sleep, and mood in healthy, normal-weight individuals. METHODS: Eleven healthy, normal-weight participants (mean age: 30 ± 9 y) completed this randomized, controlled, crossover study. Participants followed 2 isocaloric diets-an HCLF diet (55% carbohydrate, 20% fat, and 25% protein) and a KD (15% carbohydrate, 60% fat, and 25% protein)-in a randomized order for a minimum of 3 wk, with a 1-wk washout period between diets. Measures of ß-hydroxybutyrate confirmed that all participants were in a state of nutritional ketosis during post-KD assessments (baseline: 0.2 ± 0.2 mmol/L; KD: 1.0 ± 0.5 mmol/L; washout: 0.2 ± 0.1 mmol/L; and HCLF: 0.3 ± 0.2 mmol/L). Cognitive function was assessed using a validated, psychological computer-based test battery before and after each diet. Subjective measures of mood and sleep were also monitored throughout the study using validated scales. RESULTS: Three weeks of sustained nutritional ketosis, compared with the HCLF diet, had no effect on speed and accuracy responses in tasks designed to measure vigilance (speed: P = 0.39, Cohen's d = 0.26; accuracy: P = 0.99, Cohen's d = 0.04), visual learning and memory (speed: P = 0.99, Cohen's d = 0.04; accuracy: P = 0.99, Cohen's d = 0.03), working memory (speed: P = 0.62, Cohen's d = 0.26; accuracy: P = 0.98, Cohen's d = 0.07), and executive function (speed: P = 0.60, Cohen's d = 0.31; accuracy: P = 0.90, Cohen's d = 0.19). Likewise, mood, sleep quality, and morning vigilance did not differ (P > 0.05) between the dietary interventions. CONCLUSION: The results of our randomized, crossover, controlled study suggest that 3 wk of sustained nutritional ketosis had no effect on cognitive performance, mood, or subjective sleep quality in a sample of healthy individuals. This trial was registered in the Pan African Clinical Trial Registry as PACTR201707002406306.

Sleep in Women with Chronic Pain and Autoimmune Conditions: A Narrative Review.

Chronic pain and sleep disturbances are intricately intertwined. This narrative review provides comments on observations related to pain, stress-immunity, and sleep. Sleep evidence is reviewed from studies of select conditions involving pain (ie, functional somatic syndromes and autoimmune) that are predominant in women. Chronic pain and poor sleep encompass persistent stress-immune activation with systemic inflammation, cellular oxidative stress, and sick behavior indicators that increase morbidity and threaten quality of life. In painful conditions, sleep impairments are nearly ubiquitous, and exaggerated combined effects should not be underestimated or ignored, nor should crucial implications for clinical practice and research.

The effect of a ketogenic diet versus a high-carbohydrate, low-fat diet on sleep, cognition, thyroid function, and cardiovascular health independent of weight loss: study protocol for a randomized controlled trial.

BACKGROUND: Many physiological health benefits observed after following a ketogenic diet (KD) can be attributed to the associated weight loss. The KD has become more prominent as a popular health choice, not only in obese/overweight individuals, but also in healthy adults. The study aims to determine the effects of a KD, independent of weight loss, on various aspects of physiological health including: sleep, thyroid function, cognition, and cardio-metabolic health. The study will also aim to determine whether a change in basal metabolic rate may be associated with any changes observed. METHODS: Twenty healthy men and women between 18 and 50 years of age will take part in this study. In a randomized controlled, cross-over design, participants will follow two isocaloric diets: a high-carbohydrate, low-fat diet (55% CHO, 20% fat, 25% protein) and a KD (15% CHO, 60% fat, 25% protein). Each dietary intervention will last for a minimum of 3 weeks, with a 1-week washout period in between. Before and after each diet, participants will be assessed for sleep quality, cognitive function, thyroid function, and basal metabolic rate. A blood sample will also be taken for the measurement of cardio-metabolic and immune markers. DISCUSSION: The present study will help in understanding the potential effects of a KD on aspects of physiological health in healthy adults, without the confounding factor of weight loss. The study aims to fill a significant void in the academic literature with regards to the benefits and/or risks of a KD in a healthy population, but will also explore whether diet-related metabolic changes may be responsible for the changes observed in physiological health. TRIAL REGISTRATION: Pan African Clinical Trial Registry ( www.pactr.org ), trial number: PACTR201707002406306 . Registered on 20 July 2017.

Sleep Fragmentation Hypersensitizes Healthy Young Women to Deep and Superficial Experimental Pain.

The effect of sleep deprivation on pain sensitivity has typically been studied using total and partial sleep deprivation protocols. These protocols do not mimic the fragmented pattern of sleep disruption usually observed in individuals with clinical pain conditions. Therefore, we conducted a controlled experiment to investigate the effect of sleep fragmentation on pain perception (deep pain: forearm muscle ischemia, and superficial pain: graded pin pricks applied to the skin) in 11 healthy young women after 2 consecutive nights of sleep fragmentation, compared with a normal night of sleep. Compared with normal sleep, sleep fragmentation resulted in significantly poorer sleep quality, morning vigilance, and global mood. Pin prick threshold decreased significantly (increased sensitivity), as did habituation to ischemic muscle pain (increased sensitivity), over the course of the 2 nights of sleep fragmentation compared with the night of normal sleep. Sleep fragmentation did not increase the maximum pain intensity reported during muscle ischemia (no increase in gain), and nor did it increase the number of spontaneous pains reported by participants. Our data show that sleep fragmentation in healthy, young, pain-free women increases pain sensitivity in superficial and deep tissues, indicating a role for sleep disruption, through sleep fragmentation, in modulating pain perception. PERSPECTIVE: Our findings that pain-free, young women develop hyperalgesia to superficial and deep muscle pain after short-term sleep disruption highlight the need for effective sleep management strategies in patients with pain. Findings also suggest the possibility that short-term sleep disruption associated with recurrent acute pain could contribute to increased risk for future chronic pain conditions.

What we know about primary dysmenorrhea today: a critical review.

BACKGROUND: Primary dysmenorrhea, or painful menstruation in the absence of pelvic pathology, is a common, and often debilitating, gynecological condition that affects between 45 and 95% of menstruating women. Despite the high prevalence, dysmenorrhea is often poorly treated, and even disregarded, by health professionals, pain researchers, and the women themselves, who may accept it as a normal part of the menstrual cycle. This review reports on current knowledge, particularly with regards to the impact and consequences of recurrent menstrual pain on pain sensitivity, mood, quality of life and sleep in women with primary dysmenorrhea. METHODS: Comprehensive literature searches on primary dysmenorrhea were performed using the electronic databases PubMed, Google Scholar and the Cochrane Library. Full-text manuscripts published between the years 1944 and 2015 were reviewed for relevancy and reference lists were cross-checked for additional relevant studies. In combination with the word 'dysmenorrhea' one or more of the following search terms were used to obtain articles published in peer-reviewed journals only: pain, risk factors, etiology, experimental pain, clinical pain, adenomyosis, chronic pain, women, menstrual cycle, hyperalgesia, pain threshold, pain tolerance, pain sensitivity, pain reactivity, pain perception, central sensitization, quality of life, sleep, treatment, non-steroidal anti-inflammatory drugs. RESULTS: Women with dysmenorrhea, compared with women without dysmenorrhea, have greater sensitivity to experimental pain both within and outside areas of referred menstrual pain. Importantly, the enhanced pain sensitivity is evident even in phases of the menstrual cycle when women are not experiencing menstrual pain, illustrating that long-term differences in pain perception extend outside of the painful menstruation phase. This enhanced pain sensitivity may increase susceptibility to other chronic pain conditions in later life; dysmenorrhea is a risk factor for fibromyalgia. Further, dysmenorrheic pain has an immediate negative impact on quality of life, for up to a few days every month. Women with primary dysmenorrhea have a significantly reduced quality of life, poorer mood and poorer sleep quality during menstruation compared with their pain-free follicular phase, and compared with the menstruation phase of pain-free control women. The prescribed first-line therapy for menstrual pain remains non-steroidal anti-inflammatory drugs, which are effective in relieving daytime and night-time pain. CONCLUSION: Further study is needed to determine whether effectively blocking dysmenorrheic pain ameliorates risk for the development of chronic pain disorders and to explore whether it is possible to prevent the development-and not just treat-severe dysmenorrheic pain in adolescent girls. In conclusion, we demonstrate the extensive multi-factorial impact of dysmenorrhea and we encourage and direct researchers to necessary future studies.

Reduced quality of life when experiencing menstrual pain in women with primary dysmenorrhea.

Primary dysmenorrhea is the most common gynecological condition among women of reproductive age. Although dysmenorrhea has been reported to affect the ability of women to carry out daily activities, the impact of primary dysmenorrheic pain specifically on quality of life (QoL), has yet to be elucidated. We investigated whether QoL varies between women with and without severe primary dysmenorrhea, and whether QoL is impaired only during menstruation or also during pain-free phases of the menstrual cycle. Twelve women with severe primary dysmenorrhea and nine control women completed the quality of life enjoyment and satisfaction questionnaire (Q-LES-Q-SF) during menstruation and during the late follicular phase. Women with dysmenorrhea had a significant reduction in Q-LES-Q-SF scores (mean ± SD: 54 ± 18%, percentage of the total maximum possible score) when they were experiencing severe menstrual pain compared with their own pain-free follicular phase (80 ± 14%, p < 0.0001) and compared with controls during menstruation (81 ± 10%, p < 0.0001). They also rated their overall life satisfaction and contentment as poorer during menstruation. Severe menstrual pain associated with primary dysmenorrhea, therefore, impacts health-related of QoL.

The 24-h progression of menstrual pain in women with primary dysmenorrhea when given diclofenac potassium: a randomized, double-blinded, placebo-controlled crossover study.

PURPOSE: Primary dysmenorrhea, which refers to painful, spasmodic cramping in the lower abdomen just before/or during menstruation, is the most common gynecological complaint in women of reproductive age. Non-steroidal anti-inflammatory drugs have been prescribed as the first-line therapy for pain relief from dysmenorrhea. We aimed to investigate the efficacy of the daily recommended dose (150 mg) of diclofenac potassium, administered at set intervals across the first 24 h of menstruation, in treating severe menstrual pain in 24 women with severe primary dysmenorrhea. METHODS: In a randomized, placebo-controlled, double-blind cross-over study, women rated their menstrual pain intensity on a 100-mm visual analog scale across set time intervals over a 24-h period. RESULTS: Menstrual pain intensity was significantly reduced after taking the first capsule of diclofenac, and remained consistently lower (P < 0.0001), compared with initial pain intensity, in the morning (before treatment), throughout the day, evening, and into the next morning. Also, women rated their pain intensity as significantly lower (P < 0.001) at each time point across the 24-h time interval of the cycle when receiving diclofenac compared with the cycle when they received placebo. No woman required rescue medication when taking diclofenac potassium compared with six women taking rescue medications during the placebo trial. When taking only placebo, women rated their menstrual pain intensity as persistently severe across the first 24 h of menstruation. CONCLUSION: These results show that the recommended daily dose of diclofenac potassium, in three 50 mg doses across the day and evening, offers effective menstrual pain relief across 24 h, compared with placebo, in women with severe primary dysmenorrhea.

Women with dysmenorrhea are hypersensitive to experimental deep muscle pain across the menstrual cycle.

UNLABELLED: Primary dysmenorrhea is a common painful condition in women that recurs every month across the reproductive years. The recurrent nociceptive input into the central nervous system that occurs during menstruation each month in women with dysmenorrhea is hypothesized to lead to increased sensitivity to painful stimuli. We investigated whether women with primary dysmenorrhea are hyperalgesic to deep muscle pain induced by a cleanly nociceptive method of hypertonic saline injection. Pain stimulation was applied both within an area of referred menstrual pain (lower back) and at a remote site outside of referred menstrual pain (forearm) in 12 healthy women with severe dysmenorrhea and 9 healthy women without dysmenorrhea, at 3 phases of the menstrual cycle: menstruation and follicular and luteal phases. Women rated their pain severity on a 100-mm visual analog scale every 30 seconds after injection until the pain subsided. In both groups of women, menstrual cycle phase had no effect on the reported intensity and duration of muscle pain. However, women with dysmenorrhea had increased sensitivity to experimental muscle pain both at the site of referred pain and at a remote nonpainful site, as assessed by peak pain severity visual analog scale rating, area under the visual analog scale curve, and pain duration, compared to women without dysmenorrhea. These data show that women with severe primary dysmenorrhea, who experience monthly menstrual pain, are hyperalgesic to deep muscle pain compared to women without dysmenorrhea. PERSPECTIVE: Our findings that dysmenorrheic women are hyperalgesic to a clinically relevant, deep muscle pain in areas within and outside of referred menstrual pain indicates lasting changes in pain sensitivity outside of the painful period during menstruation.

Diclofenac potassium restores objective and subjective measures of sleep quality in women with primary dysmenorrhea.

STUDY OBJECTIVES: Primary dysmenorrhea is a common gynecological disorder that disrupts daytime functioning and nighttime sleep quality. We determined the effectiveness of diclofenac potassium, compared to placebo, in alleviating nighttime pain and restoring sleep architecture in women with primary dysmenorrhea. DESIGN: Randomized, double-blind, crossover study. SETTING: Sleep laboratory. PARTICIPANTS: Ten healthy women (21 +/- 1 years) with a history of primary dysmenorrhea. INTERVENTIONS: Placebo or diclofenac potassium (150 mg per day) for menstrual pain. MEASUREMENTS AND RESULTS: We assessed objective measures of sleep (polysomnography) and subjective measures of sleep quality, mood, and intensity of menstrual pain. Compared to a pain-free phase of the menstrual cycle (mid-follicular), women receiving placebo for their menstrual pain had a poorer mood (P < 0.01), decreased sleep efficiency (P < 0.05), less REM sleep (P < 0.05), more stage 1 sleep (P < 0.01), and more sleep stage changes per hour of sleep during the night. Administration of diclofenac potassium compared to placebo not only attenuated the women's menstrual pain (P < 0.05), but also increased sleep efficiency (P < 0.05) and percentage of REM sleep (P < 0.01), decreased percentage of stage 1 sleep (P < 0.05) and number of sleep stage changes per hour of sleep (P < 0.05), and improved subjective ratings of sleep quality and morning vigilance (P < 0.05). CONCLUSION: Diclofenac potassium effectively attenuates nighttime dysmenorrheic pain and restores subjective and objective measures of sleep quality to values recorded in a pain-free phase of the menstrual cycle.