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Dysregulation of sleep heightens pain sensitivity and may contribute to pain chronification. Interventions which consolidate and lengthen sleep have the potential to improve pain control. The main objective of this systematic review was to examine the effects of sleep-promoting pharmacotherapy on pain intensity in patients with chronic pain. Multiple electronic databases were searched from inception to January 2022 to identify relevant randomized controlled trials (RCTs). Two independent reviewers screened titles, abstracts, and full-text articles; extracted data; and assessed risk of bias for each included study. The GRADE approach was used to determine the strength of evidence. The search identified 624 articles. After full-text screening, 10 RCTs (n = 574 randomized participants) involving 3 pharmacologic interventions (melatonin, zopiclone, and eszopiclone) and 7 different chronic pain populations were included. Minimum clinically significant pain reduction >= 30% was reported in 4 studies. There is low-quality evidence (downgraded due to inconsistency and imprecision) that 2 to 8 weeks treatment with a sleep-promoting medication alone or in combination with an analgesic (6 trials, n = 397) decreases pain intensity compared with placebo or the same analgesic treatment alone (SMD -0.58 [95% confidence interval -1.00, -0.17], P = 0.006). Analyses of associations between changes in sleep and pain outcomes were only provided in 2 articles, with inconsistent findings. Notably, pain-relieving effects were most consistent in melatonin trials. Only 3 studies implemented polysomnography to obtain objective sleep measures. Low-quality evidence indicates that pharmacologic sleep promotion may decrease pain intensity in chronic pain populations. More research is needed to fully understand the influence of sleep-targeting interventions on pain control.

Introduction

The diagnostic process for idiopathic hypersomnia (IH) is complex due to the diverse aetiologies of daytime somnolence, ambiguous pathophysiological understanding, and symptom variability. Current diagnostic instruments, such as the multiple sleep latency test (MSLT), are limited in their ability to fully represent IH's diverse nature. This study endeavours to delineate subgroups among IH patients via cluster analysis of polysomnographic data and to examine the temporal evolution of their symptomatology, aiming to enhance the granularity of understanding and individualized treatment approaches for IH.

Methods

This study included individuals referred to the Uppsala Centre for Sleep Disorders from 2010 to 2019, who were diagnosed with IH based on the International Classification of Sleep Disorders-3 (ICSD-3) criteria, following a thorough diagnostic evaluation. The final cohort, after excluding participants with incomplete data or significant comorbid sleep-related respiratory conditions, comprised 69 subjects, including 49 females and 20 males, with an average age of 40 years. Data were collected through polysomnography (PSG), MSLT, and standardized questionnaires. A two-step cluster analysis was employed to navigate the heterogeneity within IH, focusing on objective time allocation across different sleep stages and sleep efficiency derived from PSG. The study also aimed to track subgroup-specific changes in symptomatology over time, with follow-ups ranging from 21 to 179 months post-diagnosis.

Results

The two-step cluster analysis yielded two distinct groups with a satisfactory silhouette coefficient: Cluster 1 (n = 29; 42 %) and Cluster 2 (n = 40; 58 %). Cluster 1 exhibited increased deep sleep duration, reduced stage 2 sleep, and higher sleep maintenance efficiency compared to Cluster 2. Further analyses of non-clustering variables indicated shorter wake after sleep onset in Cluster 1, but no significant differences in other sleep parameters, MSLT outcomes, body mass index, age, or self-reported measures of sleep inertia or medication usage. Long-term follow-up assessments showed an overall improvement in excessive daytime sleepiness, with no significant inter-cluster differences.

Conclusion

This exploratory two-step cluster analysis of IH-diagnosed patients discerned two subgroups with distinct nocturnal sleep characteristics, aligning with prior findings and endorsing the notion that IH may encompass several phenotypes, each potentially requiring tailored therapeutic strategies. Further research is imperative to substantiate these findings.

The impact of comorbidities in fibromyalgia (FM) and temporomandibular disorders (TMD) have been well documented, but whether TMD sub-diagnoses myalgia (MYA) and myofascial pain with referral (MFP) differ regarding comorbidity is unclear. We aimed to elucidate this by studying the presence and associations of comorbidities in FM, MFP and MYA. An extended version of the Diagnostic Criteria for TMD axis II questionnaire was used to examine demographics, pain and comorbidities in 81 patients with FM, 80 with MYA, and 81 with MFP. Patients with MFP and FM reported a higher percentage of irritable bowel syndrome (IBS), depression, anxiety, somatic symptoms, perceived stress, and insomnia compared to MYA. Patients with FM had more IBS, depression, and somatic symptom disorder versus MFP. After adjusting for confounding variables, participants with anxiety, somatic symptoms disorder, pain catastrophizing, and perceived stress, as well as a greater number of comorbidities, were more likely to have MFP than MYA, whereas FM participants were more associated with IBS, somatic symptoms and insomnia compared to MFP. The number of comorbidities was significantly associated with widespread pain but not pain duration, body mass index or being on sick leave. In conclusion, patients with MFP were more similar to those with FM regarding comorbidity and should be differentiated from MYA in clinical settings and pain management.

About 20% of patients with diabetes suffer from chronic pain with neuropathic characteristics. We investigated the multivariate associations between 92 neurology-related proteins measured in serum from 190 patients with painful and painless diabetic neuropathy. Participants were recruited from the Pain in Neuropathy Study, an observational cross-sectional multicentre study in which participants underwent deep phenotyping. In the exploration cohort, two groups were defined by hierarchical cluster analyses of protein data. The proportion of painless vs painful neuropathy did not differ between the two groups, but one group had a significantly higher grade of neuropathy as measured by the Toronto Clinical Scoring System (TCSS). This finding was replicated in the replication cohort. Analyzing both groups together, we found that a group of 11 inter-correlated proteins (TNFRSF12A, SCARB2, N2DL-2, SKR3, EFNA4, LAYN, CLM-1, CD38, UNC5C, GFR-alpha-1, and JAM-B) were positively associated with TCSS values. Notably, EFNA4 and UNC5C are known to be part of axon guidance pathways. To conclude, although cluster analysis of 92 neurology-related proteins did not distinguish painful from painless diabetic neuropathy, we identified 11 proteins which positively correlated to neuropathy severity and warrant further investigation as potential biomarkers.

Background & aims: Intensive nutritional therapy is an essential component of burn care. Regardingpost-minor burn injuries, the literature is lacking. The aim of this study was to evaluate documentednutritional therapy in relation to international guidelines after both minor and major burn injuries. The secondary aim of this study was to evaluate the adequacy of energy and protein intake compared toindividual nutritional goals post-burn injury.

Methods: A retrospective observational single-centre study including patients admitted between 2017and 2019 at a burn centre in Sweden was performed. The patients included in the study were >18 years old and in need of hospital care for > 72 h post-burn injury. Information about patients' demographics,nutritional therapy, and clinical characteristics of burn injury was collected. The patients were dividedaccording to total body surface area burnt (TBSA %) into minor burn injuries (TBSA <20%) and major burninjuries (TBSA >20%). Descriptive statistics were used to analyse data. Adherence to guidelines wasestablished by comparing 24 nutritional therapy recommendations to documented treatment. If documented nutritional treatment were in accordance with guidelines, adherence was considered high(>80%), moderate (60-79.9%) or low (<59.9%).

Results: One hundred thirty-four patients were included, 90 patients with minor burn injuries and 44patients with major burn injuries. Documented adherence to the nutritional guideline was overall low.After minor burn injury, 8% (2/24) of nutritional therapy recommendations had a high adherence (fatintake <35% of total energy intake and enteral nutrition as prioritized feeding route), 17% (4/24) amoderate adherence, and 75% (18/24) a low adherence. In patients treated after a major burn injury,there were two recommendations with documented high adherence (Vitamin C and Zinc); 25% (6/24)had moderate adherence, and 67% (16/24) had low adherence. In addition, quite a large amount ofmissing data was found.Adequacy of documented nutritional intake, compared to the individual documented goal, was 78%(±23%) for energy and 66% (±22%) for protein after minor burn injury. After major burn injury, the adequacy was 89% (±21%) for energy and 78% (±19%) for protein, respectively.

Conclusions: This study revealed low adherence to nutritional guidelines in patients treated for minorand major burn injuries. Compared to major burn injuries, lower documented adequacy for both energyand proteins was found in minor burn injuries. Given the disparity between guidelines and documentednutritional therapy, and the lack of specific guidelines for minor burn injuries, there could be aconsiderable risk of inadequate nutritional therapy post-burn injury.

Disease Related Appetite Questionnaire (DRAQ) and Eating Symptom Questionnaire(ESQ) are used to assess nutrition impact symptoms, which are symptoms that can negatively affectthe patients’ food intake. However, these questionnaires have not yet been adapted to the needsof patients recovering from burn injuries. Our aim was therefore to develop DRAQ and ESQ forassessments of nutrition impact symptoms after burn injury. A content validation index (I-CVI) foritems included in DRAQ and ESQ, regarding their relevance for possible nutrition impact symptomsin a burn-injured patient (Likert scale 1–4), was performed by an expert review group. A clarityvalidation by expert and non-expert reviewers was carried out. Two of the eleven questions inDRAQ and eight of the fourteen questions in ESQ were not considered relevant and were thereforeremoved from the questionnaires. Five additional questions were added to DRAQ and two to ESQ.A high degree of consensus on relevance (scale-content validity index average, S-CVI/Ave, 0.86 forDRAQ-burn and 0.83 for ESQ-burn) was reached in the expert group. To conclude, it is suggestedthat we use developed forms of DRAQ and ESQ (DRAQ-burn and ESQ-burn) for the assessment ofnutrition impact symptoms, specifically during the rehabilitation phase of burn-injured patients.

Introduction: Recent studies suggest an increased prevalence of chronic pain conditions and restless legs syndrome (RLS) in patients with chronic pulmonary disease (CPD). We analyzed the prevalence and risk factors for pain and RLS in a population-based sample of females with comorbid CPD.

Method: Questionnaire-based data from 2745 women aged 18–64 years were analyzed regarding comorbid CPD status (severe bronchitis, emphysema, asthma). Pain status was assessed according to symptoms reflecting severity (Visual Analogue Scale, VAS rating 0–10) and duration and spreading (limited spread or widespread) of pain. A diagnosis of RLS was defined by four validated diagnostic criteria. Anthropometrics and co-morbidities were assessed as covariates in univariate and multivariate analyses.

Results: Widespread pain was overrepresented in women with CPD (44.6 vs. 24.6%, p < 0.001). The odds ratio for widespread pain in women with CPD was 1.6 (95% confidence interval (CI) 1.2–2.2, p < 0.001) in the fully adjusted model. Severe pain (VAS rating ≥ 7) was more prevalent in females with known CPD (28.8 vs. 15.4%, p < 0.001, odd ratio 1.4 (95% CI 1.0–1.9, p = 0.029)). The prevalence of RLS was 37.4 and 23.8% in subjects with or without CPD, respectively (p < 0.001). In multivariate analysis, CPD was associated with a 30% risk increase for RLS (odds ratio 1.3 (95% CI 1.0–1.7, p = 0.04)).

Conclusion: This population-based study identified CPD as an independent risk factor for severe and widespread pain as well as for RLS. Further research addressing pathophysiological mechanisms linking CPD and chronic pain conditions/RLS is warranted.

Objectives

Quantitative sensory testing (QST) provides an assessment of cutaneous and deep tissue sensitivity and pain perception under normal and pathological settings. Approximately 2–4% of individuals undergoing groin hernia repair (GHR) develop severe persistent postsurgical pain (PPSP). The aims of this systematic review of PPSP-patients were (1) to retrieve and methodologically characterize the available QST literature and (2) to explore the role of QST in understanding mechanisms underlying PPSP following GHR.

Methods

A systematic literature search was conducted from JAN-1992 to SEP-2022 in PubMed, EMBASE, and Google Scholar. For inclusion, studies had to report at least one QST-modality in patients with PPSP. Risk of bias assessment of the studies was conducted utilizing the Newcastle Ottawa Scale and Cochrane’s Risk of Bias assessment tool 2.0. The review provided both a qualitative and quantitative analysis of the results. A random effects model was used for meta-analysis.

Results

Twenty-five studies were included (5 randomized controlled trials, 20 non-randomized controlled trials). Overall, risk of bias was low. Compared with the contralateral side or controls, there were significant alterations in somatosensory function of the surgical site in PPSP-patients. Following thresholds were significantly increased: mechanical detection thresholds for punctate stimuli (mean difference (95% CI) 3.3 (1.6, 6.9) mN (P = 0.002)), warmth detection thresholds (3.2 (1.6, 4.7) °C (P = 0.0001)), cool detection thresholds (-3.2 (-4.9, -1.6) °C (P = 0.0001)), and heat pain thresholds (1.9 (1.1, 2.7) °C (P = 0.00001)). However, the pressure pain thresholds were significantly decreased (-76 (-123, -30) kPa (P = 0.001)).

Conclusion

Our review demonstrates a plethora of methods used regarding outcome assessments, data processing, and data interpretation. From a pathophysiological perspective, the most consistent findings were postsurgical cutaneous deafferentation and development of a pain generator in deeper connective tissues.

Background

In most cases, a combination of paracetamol and ibuprofen are the optimal treatment for postoperative pain in third molar surgery. If stronger analgesia is required, opioids are traditionally administered. In day-case, surgery; however, opioids should be avoided. Thus, the anaesthetic agent S-ketamine in analgesic doses might be preferred.

Methods

The study was designed as a randomized placebo-controlled double-blind clinical trial. The study enrolled healthy subjects according to the American Society of Anaesthesiologists classification; I or II (ASA), aged 18 to 44 years, with a body weight between 50 and 100 kg. The patients were randomized into three groups where two doses of S-ketamine were compared (high: 0.25 mg/kg or low: 0.125 mg/kg) with placebo (saline).

Results

A primary outcome of the study was that VAS at 4 h postoperatively, showed no significant difference between the placebo and high-dose S-ketamine group or in the low-dose group. We found a significant difference between the groups for the first 24 h, with a lower VAS-score in the high-dose S-ketamine group. The time to when 50% had taken their first rescue medication was 12 min later in the high-dose ketamine group.

Conclusions

Pre-emptive S-ketamine 0.25 mg/kg gave a global significant reduction of pain by VAS during the first 24 h postoperatively. The time from end of surgery to first rescue medication were longer in the high-dose ketamine group compared to both low-dose ketamine and placebo groups.

Functional brain networks and the perception of pain can fluctuate over time. However, how the time-dependent reconfiguration of functional brain networks contributes to chronic pain remains largely unexplained. Here, we explored time-varying changes in brain network integration and segregation during pain over a disease-affected area (joint) compared to a neutral site (thumbnail) in 28 patients with rheumatoid arthritis (RA) in comparison with 22 healthy controls (HC). During functional magnetic resonance imaging, all subjects received individually calibrated pain pressures corresponding to visual analog scale 50 mm at joint and thumbnail. We implemented a novel approach to track changes of task-based network connectivity over time. Within this framework, we quantified measures of integration (participation coefficient, PC) and segregation (within-module degree z-score). Using these network measures at multiple spatial scales, both at the level of single nodes (brain regions) and communities (clusters of nodes), we found that PC at the community level was generally higher in RA patients compared to HC during and after painful pressure over the inflamed joint and corresponding site in HC. This shows that all brain communities integrate more in RA patients than in HC for time points following painful stimulation to a disease-relevant body site. However, the elevated community-related integration seen in patients appeared to not pertain uniquely to painful stimulation at the inflamed joint, but also at the neutral thumbnail, as integration and segregation at the community level did not differ across body sites in patients. Moreover, there was no specific nodal contribution to brain network integration or segregation. Altogether, our findings indicate widespread and persistent changes in network interaction in RA patients compared to HC in response to painful stimulation.