Background:In recent years, musculoskeletal pain (MSP) has gained widespread attention globally and has become a significant public health issue affecting people of all ages, especially those affected by adolescence. Many musculoskeletal problems have a biomechanical origin, often linked to foot type and plantar pressure. Objectives:The aim of this study is to provide new insights into the multifactorial nature of MSP by exploring its associations with foot type, plantar pressure, physical activity, psychosocial factors, and daily living habits in adolescents. Design:A cross-sectional observational study was conducted among adolescents recruited from community and schools in Guangzhou, China. Methods:Chi-square tests and logistic regression analysis were employed to investigate the associations between the prevalence of musculoskeletal pain and various factors, including foot type, plantar pressure, physical activity levels, psychosocial factors, study pressure and daily living habits like sleep duration, sleep quality, and screen time. Given the high prevalence and clinical relevance, we further analyzed factors associated with neck, back, and foot pain. Results:This study included 216 adolescents (15.83 ± 1.05 years). The analysis revealed that physical activity, sleep duration, and study pressure significantly associated with the incidence of neck pain. Emotional symptoms at the threshold or abnormal and poor sleep quality both associated with low back pain. Foot type and plantar pressure did not show statistical significance in association with overall musculoskeletal pain. However, when specific pain sites were examined, foot pain was significantly associated with maximum plantar pressure ⩾ 1000 N/dm2, average plantar pressure ⩾ 180 N, and flatfoot or high-arched foot. Conclusions:Our study found that while foot type and plantar pressure were not associated with overall musculoskeletal pain, they were significantly associated with foot pain specifically. Low physical activity, insufficient sleep, and high study pressure were linked to neck pain, while poor sleep quality and emotional symptoms were associated with low back pain. These findings highlight the multifactorial nature of musculoskeletal pain and the need for comprehensive assessments in primary care. Clinical trial number:This study was registered at Chinese Clinical Trials Registry (http://www.chictr.org.cn/) on August 12, 2024. Clinical trial number: ChiCTR2400088109.

Exercise-induced hypoalgesia is often attenuated in chronic pain. This randomized, double-blind, sham-controlled trial tested whether HD-tDCS over the left primary motor cortex enhances exercise-related hypoalgesic responses, as reflected by pressure pain threshold changes, during aerobic exercise in chronic low back pain. Fifty-two participants received active or sham HD-tDCS while cycling. Pressure pain thresholds and pain-evoked fNIRS responses were assessed before and after intervention. Active HD-tDCS produced larger pressure pain threshold increases than sham stimulation and attenuated pain-evoked activation in somatosensory, motor, and prefrontal regions. Reduced cortical activation correlated with increased pressure pain thresholds, and reduced left dlPFC activation mediated the PPT increase at the tibialis anterior site. These findings suggest that M1 HD-tDCS can augment acute exercise-related pressure pain threshold responses and modulate pain-evoked cortical activity in chronic low back pain.

Patients who undergo tracheostomy often experience respiratory muscle dysfunction and reduced airway clearance capacity, leading to reduced quality of life. While inspiratory muscle training (IMT) is effective at improving respiratory outcomes among mechanically ventilated patients, evidence about its clinical utility and safety, especially in tracheostomized populations, is limited. Moreover, the optimal IMT protocol for this patient cohort remains undefined. The aim of this study is to evaluate the effects of high-intensity interval inspiratory muscle training (HI-IMT) on diaphragmatic function, airway clearance capacity, anxiety levels, decannulation rates, quality of life, and safety outcomes among tracheostomy patients. This is a single-center, single-blind, randomized controlled trial. Seventy tracheostomized patients (aged 40–70 years, with tracheostomy for 1–3 months) will be randomly assigned to either the HI-IMT group or the control group. The HI-IMT group will receive IMT at 50

BACKGROUND:This study investigates whether anodal high-definition transcranial direct current stimulation (HD-tDCS) enhances exercise-induced hypoalgesia (EIH) and explores brain plasticity changes using functional near-infrared spectroscopy (fNIRS). METHODS:Thirty-nine participants were randomly assigned to either the active (n = 19) or sham HD-tDCS (n = 20) group. Both groups performed 25 min of moderate-intensity aerobic exercise followed by 20 min of either active or sham HD-tDCS applied to the left primary motor cortex (M1). PRIMARY OUTCOME:pressure pain threshold (PPT) at a local site. SECONDARY OUTCOMES:PPT at a remote site, cold pain threshold (CPT), and brain activation changes via fNIRS during the cold pressor test. RESULTS:Both groups showed significant increases in PPTleg (active: from 42.21 ± 11.77 N to 51.29 ± 12.75 N; sham: from 41.41 ± 9.73 N to 45.29 ± 12.05 N, p < 0.001) and PPTforearm (active: from 31.69 ± 6.06 N to 36.99 ± 6.35 N; sham: from 32.66 ± 7.34 N to 37.08 ± 10.56 N, p < 0.001). The active group showed a significantly greater increase in PPTleg compared to the sham group (9.08 ± 8.01 N vs. 3.69 ± 4.36 N, p < 0.012). fNIRS analysis revealed significant changes in specific cortical channels in the active group (p < 0.05), with a negative correlation between cortical activation in CH16 and PPTleg (r = -0.405, p = 0.011). CONCLUSION:HD-tDCS over M1 enhances EIH and is associated with increased brain activation in sensory-motor processing areas. TRIAL REGISTRATION:Clinical trial registration: ChiCTR2100048146.

Patients with chronic low back pain (CLBP) experience comorbid depression. However, the central neural processing profile of CLBP with comorbid depression remains unclear. Therefore, this study aimed to investigate specific brain abnormalities in CLBP with comorbid depression by functional magnetic resonance imaging. Fourteen CLBP patients with depression, 25 CLBP patients without depression, and 24 matched controls were included. Alterations in spontaneous brain activity and connectivity were examined through regional homogeneity (ReHo) and functional connectivity (FC). Analysis of variance and post hoc analyses among groups were conducted. Correlational analyses were performed between neuroplasticity and clinical variables. Mediation analysis was conducted to elucidate the interrelationships among brain alterations, pain, and depression. Significant between-group differences in ReHo values were found across extensive brain regions, particularly the right dorsolateral prefrontal cortex (DLPFC). Altered FC between the DLPFC and cerebellum as well as the orbitofrontal cortex was noted. ReHo and FC were associated with depression, pain catastrophizing, and back pain-related disability. ReHo values of superior frontal gyrus and its FC to cerebellum mediated the correlation between BDI and variables such as pain intensity and pain catastrophizing. CLBP patients with comorbid depression exhibit abnormal regional homogeneity in regions involving the DLPFC, and altered functional networks are observed between the DLPFC and other areas. Central changes are correlated with back pain-related outcomes and mediate the relationship between pain and depression. Our findings contribute additional insights for identifying potential biomarkers of refractory CLBP with depression comorbidity, potentially aiding in pain phenotype stratification and optimizing pain management strategies.

Alzheimer’s disease is characterized by progressive amyloid deposition and cognitive decline, yet the pathological mechanisms and treatments remain elusive. Here we report the therapeutic potential of low-intensity 40 hertz blue light exposure in a 5xFAD mouse model of Alzheimer’s disease. Our findings reveal that light treatment prevents memory decline in 4-month-old 5xFAD mice and motivation loss in 14-month-old 5xFAD mice, accompanied by restoration of glial water channel aquaporin-4 polarity, improved brain drainage efficiency, and a reduction in hippocampal lipid accumulation. We further demonstrate the beneficial effects of 40 hertz blue light are mediated through the activation of the vLGN/IGL-Re visual circuit. Notably, concomitant use of anti-Aβ antibody with 40 hertz blue light demonstrates improved soluble Aβ clearance and cognitive performance in 5xFAD mice. These findings offer functional evidence on the therapeutic effects of 40 hertz blue light in Aβ-related pathologies and suggest its potential as a supplementary strategy to augment the efficacy of antibody-based therapy. Treatments for Alzheimer’s disease (AD) remain limited. Here, the authors show that 40 hertz blue light activates a visual circuit to boost glymphatic drainage, and enhances memory, motivation, and anti-Aβ therapy efficacy in a mouse model of AD.

The impact of transcranial direct current stimulation (tDCS) on pain empathy is a subject of debate and controversy. The variations in the results could be attributed to differences in the stimulus parameters. This study aimed to examine the impact of high-definition transcranial direct current stimulation (HD-tDCS) with different intensities on pain empathy through event-related potentials (ERPs). Thirty-nine participants were recruited for the experiment, and a parallel control design was used. The participants were randomly assigned to the sham group, 1 mA stimulation group, or 2 mA stimulation group. Before the experiment, all the participants provided basic information, completed relevant questionnaires and then wore an EEG cap for the first pain empathy task. After completing the task, each group received 20 minutes of HD-tDCS stimulation over the left DLPFC region at different intensities (2 mA, 1 mA, or sham), followed by a second pain empathy task. The findings from the pain-judgment and hands-counting tasks (task 1) demonstrated that both 1- and 2-mA stimulation increased Δ-N1 amplitudes, suggesting that anodal stimulation enhances early empathic responses. The results of the pain rating task (task 2) indicate that HD-tDCS stimulation did not improve the ratings of others' pain. However, the application of 2-mA tDCS significantly increased the Δ-intensity of unpleasantness compared with that of the other two groups. This suggests that 2-mA tDCS stimulation had a notable effect on the affective dimension of empathy, specifically the perception of unpleasantness. This finding indicates that 2mA stimulation primarily enhances affective empathy, whereas its influence on cognitive empathy appears to be limited. By employing different intensities of HD-tDCS, our findings build upon and extend previous findings in the field of pain empathy. These results have the potential to offer dose recommendations for future studies employing tDCS as an intervention to increase pain empathy.

PURPOSE:Cancer-related pain (CRP) is one of the most challenging disorders among cancer survivors. Non-invasive brain stimulation (NIBS) is an emerging technique for alleviating pain. Although there is evidence suggesting that NIBS can alleviate CRP, higher level evidence is still required to further substantiate its efficacy and safety. This study aimed to evaluate the efficacy of NIBS interventions for CRP via a meta-analysis. METHODS:Databases such as MEDLINE, PubMed, Embase, CINAHL, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, China National Knowledge Infrastructure were systematically searched using key terms related to pain, cancer, and NIBS. The primary outcome was pain intensity and the secondary outcome was depression. After extracting and assessing data from the included literature, we performed Meta-analysis using RevMan 5.4.1 software. RESULTS:The results encompassed 11 randomized controlled trials papers, involving 714 patients. The Meta-analysis findings indicated that NIBS demonstrated a significant reduction in pain intensity scores {SMD -0.72 [95% confidence interval (CI), -1.00 to -0.43], P < 0.00001}. NIBS also had a notable effect on depression [SMD -0.62 (95% CI, -0.93 to -0.31), P = 0.0004]. However, subgroup analysis revealed that one single session of NIBS did not show statistical significance in analgesic effect. Furthermore, no matter targeting the M1 and DLPFC areas, as well as using either rTMS or tDCS, resulted in significant reductions in pain intensity. CONCLUSION:NIBS exhibited a promising trend in alleviating CRP and enhancing treatment effectiveness. Nonetheless, due to limitations in the quantity and quality of the included studies, these findings warrant further validation through additional research.

Rheumatoid arthritis (RA) patients have a high prevalence for depression. On the other hand, comorbid with depression is associated with worse prognosis for RA. However, little is known about the underlying mechanisms for the comorbidity between RA and depression. It remains to be elucidated which brain region is critically involved in the development of depression in RA, and whether alterations in the brain may affect pathological development of RA symptoms. Here, by combining clinical and animal model studies, we show that in RA patients, the level of depression is significantly correlated with the severity of RA disease activity and affects patients' quality of life. The collagen antibody-induced arthritis (CAIA) mouse model of RA also develops depression-like behaviors, accompanied by hyperactivity and alterations in gene expression reflecting cerebrovascular disruption in the lateral habenula (LHb), a brain region critical for processing negative valence. Importantly, inhibition of the LHb not only alleviates depression-like behaviors, but also results in rapid remission of RA symptoms and amelioration of RA-related pathological changes. Together, our study highlights a critical but previously overlooked contribution of hyperactive LHb to the comorbidity between RA and depression, suggesting that targeting LHb in conjunction with RA treatments may be a promising strategy for RA patients comorbid with depression.

Purpose:Central sensitization (CS) is commonly seen in chronic pain disorders, including neuropathic pain. However, there exist inconsistencies concerning the presence of CS in chronic pain secondary to carpal tunnel syndrome (CTS). CS and neuropathic pain manifestations in CTS remain not well established. Therefore, this study aims to investigate the CS and pain profiles in patients with CTS and to explore the potential determinants associated with CS. Patients and Methods:Patients with suspected CTS symptoms lasting 3 months or above and healthy controls were enrolled. History, physical examinations, and nerve conduction studies were employed to confirm the diagnosis and severity of median nerve dysfunction. The central sensitization inventory (CSI) was used to screen CS. Other outcomes included neuropathic pain, CTS-specific symptom severity and functions, emotion, and health-related quality of life. Between-group comparisons were conducted in terms of the CS presence. Logistic regression analysis was performed to identify determinants associated with CS. Results:Over 60% of participants with CTS were found with clinical CS, significantly higher than that in the control group. More than 70% of the CTS participants were identified to have possible or very likely neuropathic pain components. In addition, one-fourth of CTS cases had depression or anxiety. Anxiety was associated with an increased risk of developing CS in CTS (adjusted OR=1.31, 95% CI 1.08-1.59), whereas higher self-perceived general health rating was negatively associated with the presence of CS (adjusted OR=0.92, 95% CI 0.88-0.97) in the multivariate adjusted regression model. Conclusion:CS is prevalent in patients with CTS. Predominant neuropathic pain characteristics were uncovered in CTS patients as well as comorbid psychological distress. Significant association was found between anxiety and CS presence. Self-perceived general health was inversely related to CS. Further research is warranted to explore the mechanisms of anxiety and central pain processing in painful entrapment neuropathy.

Knee osteoarthritis (OA) is a prevalent disabling disorder that involves changes in articular cartilage damage, subchondral bone remodeling, synovitis, and abnormal infrapatellar fat pad (IPFP). Due to the complicated etiology and numerous phenotypes of knee OA, limited improvement is achieved for treatments among knee OA patients with different phenotypes. Inflammatory OA phenotype is a typical knee OA phenotype, and individualized treatment targeting inflammation is a promising way to obtain an optimal therapeutic effect for people with inflammatory knee OA phenotype. Glucocorticoid is a traditional anti-inflammatory drug for knee OA, and intra-articular glucocorticoid injections are recommended clinically. However, emerging evidence has shown that repeated intra-articular glucocorticoid injections in the long term would induce cartilage loss. IPFP and its adjacent synovium are considered as the main source of inflammation in knee OA. This GLITTERS trial aims to investigate if a glucocorticoid injection into the IPFP is effective and safe over 12 weeks among knee OA patients with an inflammatory phenotype. GLITTERS is a multicenter, double-blinded, randomized, and placebo-controlled clinical trial among knee OA patients with both Hoffa-synovitis and effusion-synovitis. Sixty participants will be allocated randomly and equally to either the glucocorticoid group or the control group. Each group will receive an injection of glucocorticoid or saline into the IPFP with an intra-articular hyaluronic acid injection as a background treatment at baseline and be followed at 4, 8, and 12 weeks. The primary outcomes will be changes in knee pain on a visual analog scale and effusion-synovitis volume measured on magnetic resonance imaging (MRI). The secondary outcomes will be changes in the total score of Western Ontario and McMaster Universities Osteoarthritis Index score, MRI-detected Hoffa-synovitis score, quality of life, pain medication use, IPFP volume, and the incidence of adverse reactions. Data analyses based on the intention-to-treat principle will include mixed-effects regressions, Wilcoxon rank-sum tests, and chi-square tests (or Fisher’s exact test). GLITTERS may provide high-quality evidence for the efficacy and safety of ultrasound-guided glucocorticoid injections into IPFP among people with inflammatory knee OA in a short term. The results of this trial are expected to provide a reliable reference for a longer-term risk–benefit profile of this treatment in the future. ClinicalTrials.gov NCT05291650. Registered on 23 March 2022.

Diabetes can be classified as type 1, type 2, and gestational diabetes mellitus (GDM). It has been reported that children born from mothers with GDM present motor impairment, however, underlying mechanisms of GDM-induce fetal neurological diseases remain unknown. In this study, NOD (nonobese diabetic) mice were used to construct the GDM model; after 2 weeks of gestation, thalamocortical axon development of fetal was evaluated by immunofluorescence. PCR of LRRC4C was used to confirm axon development of the thalamus cortex. RNA array was used to predict possible targets affected by GDM during fetal neurodevelopment. Western blot was used to investigate the underlying mechanism, PI3K inhibitor, and MAPK inhibitor was used to determine key pathway involved in this model, in vitro axonal growth was evaluated using neural stem cells, tactile sensory behavior of offspring was assessed to confirm neurological influence further. The result shown that maternal diabetes significantly suppressed axonal development of fetal thalamus cortex, PCR array of GDM fetal brain indicated that upregulation of GLP-1R compared with normal fetal, ELISA confirmed that GLP-1 level was decreased in GDM maternal serum compared with that of wild type pregnant mice. In vitro study observed enhanced axonal elongation after supplements of GLP-1 analog, GLP-1 analog PI3K-dependently active ROCK1 activity, IP injection of GLP-1 analog could partly reverse GDM-induced suppression of fetal thalamocortical axon development and improve tactile sensory behavior of GDM offspring. Our study provided a novel mechanism of GDM induced-neurological diseases and predicted GLP-1 as possible prevention supplement during gestation.

Background Aging is a significant risk factor in chronic pain development with extensive disability and greater health care costs. Mind-body exercise (MBE) has been scientifically proven to affect the pain intensity and physical health. Objectives To assess the effects of MBE modes (Tai Chi, yoga, and qigong) for treating chronic pain among middle-aged and old people, compared with nonactive and active treatment, as well as function, quality of life, and adverse events. Methods We searched PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chinese Scientific Journals Full-Text Database (VIP) till March 2022. No restrictions were chartered within the year and language of publication. We included randomized controlled trials of MBE treatment in middle-aged and elderly people with chronic pain. The overall certainty of evidence was evaluated by using the GRADE approach. Results A total of 17 studies ( n = 1,332) were included in this review. There was low-certainty evidence indicating that MBE had a moderate effect on reducing pain compared with the nonactive and active control group (standard mean difference (SMD): −0.64, 95% confidence interval (CI): −0.86 to −0.42, P < 0.001). Very-low-certainty evidence showed that the pooled SMD for the functional improvement was −0.75 (95% CI: −1.13 to −0.37, P < 0.001). Low-certainty evidence presented that no influence was observed in physical component summary (SMD: 0.23, 95% CI: −0.16 to 0.62, P = 0.24) and mental component summary (SMD: −0.01, 95% CI −0.39 to 0.36, P = 0.95). Conclusion Our results indicated that MBE was an effective treatment for reducing symptoms of middle-aged and elderly people with chronic pain compared with nonactive and active control groups. TC and qigong had obvious benefits for knee osteoarthritis in self-reported function, but the efficacy of chronic low back pain was uncertain. No significant benefit of MBE on quality of life in older adults with chronic pain was found. More high-quality RCTs should be conducted to explore the efficacy and mechanism of MBE on chronic pain in middle-aged and elderly people from various dimensions, such as affective and cognitive dimensions. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=316591 , identifier CRD42022316591.

BackgroundThere were limited studies that directly compare the outcomes of various mind-body exercise (MBE) therapies on chronic non-specific low back pain (CNLBP).ObjectivesTo compare the efficacy of the four most popular MBE modes [Pilates, Yoga, Tai Chi (TC), and Qigong] in clinically CNLBP patients, we conducted a systematic review and network meta-analysis (NMA).MethodsWe searched databases for eligible randomized controlled trials (RCTs) (from origin to July 2022). RCTs were eligible if they included adults with CNLBP, and implemented one or more MBE intervention arms using Pilates, yoga, TC, and qigong. In addition, pain intensity and physical function were evaluated using validated questionnaires.ResultsNMA was carried out on 36 eligible RCTs involving 3,050 participants. The effect of exercise therapy on pain was in the following rankings: Pilates [Surface under cumulative ranking (SUCRA) = 86.6%], TC (SUCRA = 77.2%), yoga (SUCRA = 67.6%), and qigong (SUCRA = 64.6%). The effect of exercise therapy on function: Pilates (SUCRA = 98.4%), qigong (SUCRA = 61.6%,), TC (SUCRA = 59.5%) and yoga (SUCRA = 59.0%).ConclusionOur NMA shows that Pilates might be the best MBE therapy for CNLBP in pain intensity and physical function. TC is second only to Pilates in improving pain in patients with CNLBP and has the value of promotion. In the future, we need more high-quality, long-term follow-up RCTs to confirm our findings.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=306905, identifier: CRD42022306905.

Background Work-related neck pain (WRNP) is a leading cause of disability and absenteeism. Patients with neck pain often have neck muscle tenderness and decreased cervical mobility, which are sometimes combined with psychosocial issues, such as pain catastrophising, thereby reducing their work ability. Whilst multidisciplinary treatments, including pharmacological interventions, manual therapy and specific neck exercises, have produced positive outcomes, effective personalised treatment modalities are still needed. Furthermore, manual therapies using the hands can bring fatigue to therapist. Occiflex is a computerised device that can provide personalised segmental joint mobilisation based on symptoms and injury of the patient and then provide a medium range of joint activities to improve range of cervical motion. This study aims to compare the effect of computerised mobilisation performed with Occiflex with that of traditional manual therapy on WRNP. Methods We will conduct a prospective randomised controlled trial including 150 patients with WRNP. These patients will be randomly assigned to one of three groups: (i) home exercise (TE), (ii) home exercise plus Occiflex therapy and (iii) home exercise plus manual therapy delivered by a physical therapist. Ten treatment sessions will be performed in four weeks. During the trial, these patients will receive only the assigned treatment and the standard patient education and will be asked not to use any analgesics unless strictly necessary. Assessments by trained evaluators will occur at baseline, week 4 and week 12. The primary outcome measures will include visual analogue scale (VAS) for pain and neck disability index (NDI) at each time point. Secondary outcome measures will include cervical range of motion (CROM), pressure pain threshold (PPT), global perceived effect (GPE) and sick leave. Group by time differences will be analysed using linear mixed models with repeated measures. Discussion This protocol describes the methods for a randomised controlled trial to compare the effectiveness of computerised versus manual mobilisation techniques in treating WRNP. The results will provide an alternative method (Occiflex) that is possibly effective for treating neck pain whilst minimising the manual work done by therapists. Trial registration The study protocol was retrospectively registered at http://www.chictr.org.cn (registration number: ChiCTR2100053076) on November 10, 2021.

Total hip and knee arthroplasty have become two of the most prevalent surgeries under the general background. Home-based exercise program has been proven to be an effective way to help patients improve function and mobility after discharging from hospital. However, the adherence towards the prescribed exercises is unsatisfactory. Unfortunately, there are few studies to prove whether this recommended method is effective enough to help make a difference on their adherence. This study aims to figure out whether tailored-made rehabilitative exercise program will influence the training adherence of old patients who underwent total hip and knee arthroplasty. Twelve old participants who met our criteria and corporately completed the online evaluation were included. Exercise program included a fixed one or a tailored-made one, which would be sent to different groups of participants after randomization and grouping randomly. According to their stage which they were recovering from, they were sent the prescribed exercise program and were asked to finish it following the recommended frequency at home. WOMAC scale, Time and Go test (TUG), Single leg stance (SLS) were tested before and after the intervention. For the primary outcomes, the indicators of adherence were tested after two-week intervention. After two-week follow-up, a positive tendency that tailored-made program could improve participants' adherence towards exercise was found. The health-related outcome and self-reported satisfaction appeared to be better in the tailored-made group. However, we found no statistical difference of the secondary outcomes in each groups' before-after observation except the single leg stance test $(\mathbf{p}=0.043)$ and function scores of WOMAC scale in experimental group $(\mathbf{p}=0.043)$ . Tailored-made exercise program, compared with the given fixed exercise one, appears to contribute to the improvement of patients' adherence towards exercises after the total hip and knee arthroplasty in a 2-week training period.

Major depressive disorder is one of the most common mental health conditions. Meningeal lymphatics are essential for drainage of molecules in the cerebrospinal fluid to the peripheral immune system. Their potential role in depression-like behaviour has not been investigated. Here, we show in mice, sub-chronic variable stress as a model of depression-like behaviour impairs meningeal lymphatics in females but not in males. Manipulations of meningeal lymphatics regulate the sex difference in the susceptibility to stress-induced depression- and anxiety-like behaviors in mice, as well as alterations of the medial prefrontal cortex and the ventral tegmental area, brain regions critical for emotional regulation. Together, our findings suggest meningeal lymphatic impairment contributes to susceptibility to stress in mice, and that restoration of the meningeal lymphatics might have potential for modulation of depression-like behaviour.

BackgroundChronic pain is often accompanied by emotional dysfunction. Transcranial direct current stimulation (tDCS) has been used for reducing pain, depressive and anxiety symptoms in chronic pain patients, but its therapeutic effect remains unknown.ObjectivesTo ascertain the treatment effect of tDCS on pain, depression, and anxiety symptoms of patients suffering from chronic pain, and potential factors that modulate the effectiveness of tDCS.MethodsLiterature search was performed on PubMed, Embase, Web of Science, and Cochrane Library from inception to July 2022. Randomized controlled trials that reported the effects of tDCS on pain and depression and anxiety symptoms in patients with chronic pain were included.ResultsTwenty-two studies were included in this review. Overall pooled results indicated that the use of tDCS can effectively alleviate short-term pain intensity [standard mean difference (SMD): −0.43, 95% confidence interval (CI): −0.75 to −0.12, P = 0.007] and depressive symptoms (SMD: −0.31, 95% CI, −0.47 to −0.14, P < 0.001), middle-term depressive symptoms (SMD: −0.35, 95% CI: −0.58 to −0.11, P = 0.004), long-term depressive symptoms (ES: −0.38, 95% CI: −0.64 to −0.13, P = 0.003) and anxiety symptoms (SMD: −0.26, 95% CI: −0.51 to −0.02, P = 0.03) compared with the control group.ConclusiontDCS may be an effective short-term treatment for the improvement of pain intensity and concomitant depression and anxiety symptoms in chronic pain patients. Stimulation site, stimulation frequency, and type of chronic pain were significant influence factors for the therapeutic effect of tDCS.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=297693, identifier: CRD42022297693.

Empathy is essential for human survival and social interaction. Although mindfulness-based interventions (MBIs) have been used to improve empathy in healthy populations, its therapeutic efficacy remains unknown. This study aims to investigate the therapeutic effects of MBIs on empathy in a healthy population and the potential factors affecting the efficacy of MBIs. The literature search focused on PubMed, Embase, Web of Science, Cochrane Library, and CNKI from inception to September 2022. Randomized controlled trials and quasi-experimental studies reporting the effects of using MBIs on empathy in healthy populations were included. A total of 13 studies were included in this review. Results of the meta-analysis showed that MBIs improved empathy (SMD, 0.372, 95% CI, 0.164-0.579, p = 0.001) in the healthy population compared with that in the control group. Moreover, results of the subgroup analysis showed that intervention dose (over 24 h vs. under 24 h), format (online vs. offline), and types (different types) were important factors affecting treatment outcomes. This comprehensive review suggests that MBIs are effective treatment for empathy in healthy population. Future research should markedly focus on large-sample, rigorously designed experiments to explore the long-term effects of MBIs on empathy and to elucidate the underlying mechanisms of MBIs. This study provides a reference for the daily application of MBIs.