The current preregistered study compared subjective, autonomic, and neurophysiological correlates of nocebo hyperalgesia across 3 groups: Direct Experience (N = 20), Social Learning (N = 20), and Control (N = 20). Participants first underwent a Learning-Phase, where an association between treatment cues and painful thermal stimulation was established. Conditioned responses, induced via social or direct experience, were assessed during the Test-Phase, relative to the control comparator. Pain perception, autonomic arousal, and brain activity were measured via visual analogue scale, electrodermal activity, facial action units, and electroencephalography. Both direct and social learning produced significant nocebo hyperalgesia, as indicated by increased pain ratings, autonomic arousal, and modulation of event-related potentials. Increased N2 amplitude, associated with nociceptive processing, was comparable across the 2 conditioned groups, demonstrating expectancy-driven changes in brain activity irrespective of learning type. Although social learning elicited stronger nocebo hyperalgesia in subjective ratings, direct experience was associated with heightened autonomic response and greater activation of facial action units associated with pain during the Learning-Phase. Differences in the trajectory of the autonomic response during the Test-Phase were also observed, with phasic responses diminishing for direct experience but persisting social learning. These findings highlight the role of social information in shaping maladaptive pain responses and highlight the need to mitigate nocebo effects in clinical settings where maladaptive health outcomes can be both directly experienced and socially expressed. By demonstrating distinct behavioural and physiological patterns associated with direct and social learning, this research contributes to understanding the mechanisms underlying expectancy-driven pain modulation.

Athletes can be profoundly impacted by their environment and support system. For young, injured athletes, parents may wield significant influence over their treatment and recovery, yet may hold divergent perceptions of the athletes' condition. When using the Patient-Reported Outcomes Measurement Information System (PROMIS) metrics, parents and athletes will have differing perceptions about how the athletes are affected by their injury. Cohort study; Level of evidence, 3. This study was approved by our institutional review board. In our clinics, each child (age, 8-17 years) routinely takes a series of PROMIS questionnaires. For study purposes, at 1 sports clinic visit per child, we had an accompanying parent independently complete the same PROMIS metrics on the child's behalf. We then formed dyads from each athlete/parent response and used these dyads for analysis to quantify differences in their understanding. Generalized estimating equations were used to analyze differences between members of the dyads (correlated data). The total number of dyads examined was 387. There were 201 female athletes, 186 male athletes, 302 female parents, and 85 male parents. The mean age of both male and female athletes was 14 years. Across all dyads, parents rated pain interference as worse than patients did, by a mean of 5 points (mean score, 50.03 vs 45.46, respectively; P < .001). Significant differences were also noted in peer relationships, mobility, and upper-extremity PROMIS domains. In all domains, parents rated the patients as doing worse than the athletes did themselves. When examined by sport, parents of athletes in football, soccer, gymnastics, and basketball rated pain interference as worse. Parents of athletes treated both operatively and nonoperatively rated pain interference as higher, and parents of both sexes rated pain interference as higher. Parents of injured athletes perceive their children to be more affected by pain than the athletes themselves. Parents also perceive injured athletes to have worse function across all domains than the athletes themselves do.

Background: Temporomandibular disorders (TMDs) are multifactorial conditions influenced by physical, psychological, and behavioral factors. Emotional distress, altered pain perception, and maladaptive coping strategies contribute to TMD pathology. This study examined psychological and somatosensory correlates of TMDs, focusing on anxiety, somatosensory amplification, and coping styles. Methods: This cross-sectional study included 108 patients with TMDs (76 females, 32 males; mean age 33.98 ± 7.20 years) and 112 healthy controls (58 females, 54 males; mean age 34.25 ± 6.85 years). Anxiety was assessed using the Hospital Anxiety and Depression Scale–Anxiety subscale (HADS-A), somatosensory amplification with the Somatosensory Amplification Scale (SSAS), and coping strategies with the Coping Orientation to Problems Experienced (COPE) Inventory. Pain intensity and symptom duration were measured using the Visual Analog Scale (VAS). Group differences were analyzed using independent-samples t-tests and chi-square tests. Pearson correlation and multivariate regression analyses were conducted within the TMD group to identify predictors of somatosensory amplification. Ethical approval was obtained from Cappadocia University. Results: Patients with TMDs showed significantly higher anxiety (HADS-A: 11.42 ± 3.85 vs. 6.18 ± 2.90, p &lt; 0.001) and somatosensory amplification (SSAS: 31.75 ± 7.92 vs. 20.84 ± 8.33, p &lt; 0.001) compared with controls. The TMD group reported greater use of emotion-focused and maladaptive coping strategies (p ≤ 0.01), while problem-focused coping did not differ. Pain intensity (VAS: 6.48 ± 1.72) and symptom duration (4.62 ± 2.74 years) were positively correlated with anxiety, somatosensory amplification, and maladaptive coping (all p &lt; 0.001). Regression analyses identified pain intensity and anxiety as significant predictors of somatosensory amplification, with female gender and older age also contributing. Conclusions: These findings support a biopsychosocial model of TMDs, highlighting interactions among pain, emotional distress, somatosensory amplification, and coping strategies. Integrative treatments addressing both physical and psychological factors may improve outcomes.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease characterized by complex pain mechanisms that extend beyond inflammation. Although inflammatory nociceptive pain - primarily mediated by pro-inflammatory cytokines - represents the classic pathway and therapeutic target, many patients continue to experience pain despite suppression of inflammation. This residual pain often reflects non-inflammatory processes, including nociplastic and neuropathic pain. Central sensitization, a key mechanism of nociplastic pain, contributes to pain amplification and poor response to treatment. Fibromyalgia, considered the typical phenotype of nociplastic pain, can co-occur with axSpA and is associated with increased symptom burden and reduced efficacy of anti-inflammatory therapies. Neuropathic pain, albeit less common, can result from structural complications and requires targeted therapeutic approaches. In addition, biological sex differences further influence pain perception and treatment outcomes: female patients report more widespread pain, show higher rates of central sensitization and have a worse response to biologic therapies than male patients. Current treatment paradigms are effective for inflammation-driven symptoms but often fail to address the broader spectrum of pain phenotypes in axSpA. Future work should include the development of biomarkers to differentiate pain mechanisms, the refinement of assessment tools and the evaluation of multimodal therapies that target both inflammation and pain processes. This evolving understanding necessitates a shift from an inflammation-centric to a mechanism-informed approach to pain management in axSpA.

Maintaining an optimal nociception-analgesia balance is essential in clinical anesthesia. Traditional monitoring relies on brainstem reflexes, whereas electroencephalographic (EEG) indices, such as alpha power attenuation and phase-amplitude coupling (PAC), show promise as markers of nociceptive processing. However, their physiological mechanisms and relationship to postoperative pain remain unclear. This prospective cohort study included 58 patients undergoing laparoscopic surgery under either conventional general anesthesia or general anesthesia combined with a transversus abdominis plane block. Intraoperative EEG recordings were analyzed for frequency-band power and PAC across surgical stages (incision, insufflation, and post-opioid administration). Generalized estimating equations with Bonferroni post-hoc correction were used to assess EEG patterns and their association with postoperative pain. The alpha band power and modulation index of delta-alpha PAC decreased during surgical incision, insufflation, followed by recovery after opioid administration. While alpha power changes did not differentiate the effects of the nerve block, delta-alpha PAC changes significantly reflected nerve block effectiveness during incision (coefficient: 0.81; 95% CI, 0.11-1.51; P = 0.02). However, no association was observed between perioperative EEG patterns and postoperative pain scores. Laparoscopic surgical stimulation reduces EEG alpha power and delta-alpha PAC. Delta-alpha PAC demonstrated greater sensitivity than alpha power measures in distinguishing nociceptive input and reflecting the nerve block effects, suggesting its potential as an intraoperative nociception-analgesia marker. However, perioperative EEG patterns showed limited value in predicting postoperative pain, suggesting that postoperative pain perception is shaped by more complex mechanisms requiring further investigation.

Impact of therapeutic play and music therapy on dental anxiety and pain perception in pediatric patients: a clinical study.

Ankylosing Spondylitis (AS) is a chronic, inflammatory rheumatic disease primarily affecting the axial skeleton. While the physical manifestations are well-documented, the psychological burden is often under-recognized. This comprehensive review aims to synthesize current evidence on the prevalence, etiology, and impact of psychological comorbidities, particularly depression, anxiety, and reduced health-related quality of life (HRQoL), in patients with AS. A systematic literature search was conducted in PubMed, Scopus, and Web of Science databases for articles published between 2000 and 2024. Search terms included "ankylosing spondylitis," "psychology," "depression," "anxiety," "quality of life," "fatigue," "sleep," and "coping." Studies were included if they focused on adult human subjects with AS and assessed psychological outcomes. The reviewed literature consistently demonstrates a high prevalence of psychological distress in AS, with pooled estimates of depression and anxiety significantly higher than in the general population. Key factors contributing to this burden include chronic pain, fatigue, sleep disturbances, functional limitations, and disease activity. Furthermore, psychological factors, such as catastrophizing and passive coping strategies, are identified as significant mediators of pain perception and disability. The bidirectional relationship between psychological state and disease activity creates a vicious cycle that adversely affects treatment adherence and overall prognosis. Psychological comorbidity is a prevalent and debilitating aspect of AS that warrants systematic screening and integrated management. A multidisciplinary approach, combining pharmacological therapy with psychological interventions (e.g., Cognitive-Behavioral Therapy) and physical rehabilitation, is essential to address the biopsychosocial complexity of the disease and improve patient outcomes.

Background and purpose Myofascial pain syndrome is a common condition that causes persistent pain in the neck and head, often making everyday movements difficult and limiting daily life. In this study, we’ll explore which treatment works best, dry needling, shockwave therapy, or convectional physiotherapy, when combined with targeted exercises. Over five sessions, we’ll measure how well each approach reduces pain, boosts muscle strength, and improves flexibility. Material and methods We enrolled 99 people with chronic head and neck pain and divided them randomly into three groups. The first group received standard physiotherapy along with targeted exercises, the second group got dry needling in addition to standard therapy and exercises, and the third group received shockwave therapy combined with the same standard physiotherapy and exercise. To measure progress, we looked at pain perception (using the Pain Catastrophizing Scale), neck function (via the Neck Disability Index), muscle strength, and range of motion. Results The best results in lateral flexion (p &lt; 0.001, p = 0.004) and in neck extensor strength (p = 0.043) showed dry needling (DN) with standard physiotherapy and a standardized exercise program (active cervical movements, isometric strengthening, and stretching). However, it was less effective in reducing neck disability (NDI) compared to Shockwave Therapy (SW) combined with physiotherapy and to standard Physiotherapy (SP) alone (p &lt; 0.001), possibly due to temporary discomfort at the start of treatment. All three groups followed the same exercise regimen to maintain consistency. Conclusions Shockwave therapy (SW) delivered the best results overall. It not only boosted neck strength and flexibility more than dry needling (DN) and standard physiotherapy (SP), but also made a bigger difference in reducing neck-related limitations in daily life. DN also improved cervical flexor strength and lateral mobility. All groups followed the same structured exercise program. While SP was beneficial, it was less effective than shock wave and dry needling in most measures.

Transauricular vagal nerve stimulation (taVNS) is gaining interest as a chronic pain treatment due to its convergence with nociceptive pathways. Although pain-modulation by taVNS has been demonstrated, this research often lacks the use of active control or does not simultaneously explore effects on associated interoceptive pathways or vagal activation. This double-blind, active-controlled, cross-over study aimed to corroborate the pain-modulating effect of taVNS whilst further investigating cardioception and vagal-activation markers. Thirty healthy individuals underwent 20 minutes of continuous 25-Hz electrical stimulation of the left concha cymba (taVNS) or earlobe (active control). Stimulation intensity was individually adjusted at two-thirds between perception and suprapain thresholds. Assessments were obtained before, immediately after, and 30 minutes after stimulation. These included pressure pain sensitivity measures including, pressure pain perception, detection, tolerance thresholds and conditioned pain modulation (CPM) as well as heart rate variability (HRV), pupillometry and cardioception measures. Although stimulation intensities were higher for control stimulation than taVNS (P < 0.001), participants reported no significant differences in subjective perception of stimulation or in their beliefs regarding the effects of the stimulations on the assessments. Compared to control stimulation, taVNS did not significantly modulate pressure pain sensitivity, cardioception, HRV, or pupillometry. Explorative analysis revealed a negative correlation between taVNS-associated changes in CPM and parasympathetic-HRV (P = 0.005), supporting a potential link between pain modulation and vagal activation. Although the findings offer partial support for the proposed vagal mechanism of taVNS, they highlight the limited understanding of which parameters and when stimulation exerts effects.

Cervical cancer is one of the most common cancers affecting women in Indonesia. Management of cervical cancer generally involves chemotherapy, which often causes pain, especially in advanced stages. Approximately 50-70% of cervical cancer patients experience persistent pain. Unmanaged pain can decrease quality of life, limit daily activities, and cause psychological problems such as anxiety and depression, as well as physical disturbances including sleep problems and reduced appetite. Therefore, complementary non-pharmacological interventions are needed to support pain management. Slow Stroke Back Massage (SSBM) is a nursing intervention that promotes relaxation and reduces pain perception. This nursing care aimed to apply SSBM as an evidence-based nursing intervention to reduce pain in cervical cancer patients. The method used was a case study with the application of Evidence-Based Practice Nursing. The subject was a cervical cancer patient experiencing pain. The SSBM intervention was administered once daily for 3 consecutive days. Pain intensity was measured using the Numeric Rating Scale. The results showed that the average pain score before the SSBM intervention was 4, while after the intervention it decreased to 2. Patient observations indicated reduced pain intensity and increased comfort after the intervention. In conclusion, SSBM is an effective non-pharmacological pain

Objective To determine the effect of episiotomy wound care and genital hygiene training on episiotomy wound healing and pain perception. Method This randomized controlled trial was carried out in the postpartum service of the medical faculty hospital between March 2022 and April 2022. 128 women who underlap vaginal episiotomy were randomly assigned to the experimental (n=64) and control (n=64) group. The women who gave birth in the experimental group were given episiotomy wound care and genital hygiene training. Routine postpartum care was given to the women who gave birth in the control group. The data were collected using the personal information form, the episiotomy area evaluation scale (REEDA score) and the Visual Analog Scale (VAS). Results According to the REEDA Scale (redness, edema, ecchymosis, discharge, approximation) of the wound healing status of the episiotomy area of the groups on the fifth(excluding ecchymosis) and 15th days postpartum, it was determined that the women in the education group healed faster than the women in the control group (p

Previous studies have identified an association between dental anxiety and pain perception; however, the nature of this relationship in the context of oral implant surgery, particularly with respect to pain perception across multiple time points, remains unclear. This study aimed to examine the association between dental anxiety and peak pain perception following oral implant surgery. We conducted a prospective observational study involving 332 patients undergoing oral implant surgery. Pain perception was evaluated using a Visual Analogue Scale at five time points: preoperatively (T0), intraoperatively (T1), and at 6 h (T2), 24 h (T3), and 7 days postoperatively (T4). Dental anxiety was assessed with the Modified Dental Anxiety Scale. Logistic regression analysis was conducted to investigate the association between dental anxiety and peak pain perception. A generalized additive model was used to identify nonlinear associations, and a segmented logistic regression model was employed to identify break points. The mean score for pain perception increased from 0.26 ± 0.87 at T0 to 4.36 ± 1.70 at T2, then gradually decreased to 2.55 ± 1.34 at T3 and 0.55 ± 0.80 at T4, where T2 was the time point of peak pain intensity. Logistic regression analysis revealed that the odds ratio (OR) for the association between dental anxiety and pain perception was 1.38 (95% CI: 1.26, 1.53), indicating a 38% increase in the likelihood of pain perception for each one-unit increase in dental anxiety score. A nonlinear relationship was observed, with a break point identified at a dental anxiety score of 14.01. Below this threshold, the odds of pain perception increased substantially with increasing anxiety (OR = 1.51, 95% CI: 1.34, 1.69; p < 0.001). However, beyond this point, the level of anxiety was not associated with pain perception risk (OR = 0.91, 95% CI: 0.76, 1.07; p > 0.05). A nonlinear relationship was observed between dental anxiety and pain perception following oral implant surgery. Even at subclinical levels, elevated anxiety was associated with an increased likelihood of pain perception. These findings highlight the importance of early identification and management of dental anxiety to improve postoperative pain control. Further research is warranted to evaluate the clinical utility of integrating anxiety assessment into preoperative care.

Rett Syndrome (RTT), a neurodevelopmental disorder predominantly affecting females, is characterised by evolving symptoms impacting motor and sensory domains. Herein, we present a study of longitudinal analyses, from 2- to 6-month of age, of Mecp2 heterozygous (Mecp2-het) female mice to comprehensively explore pain perception in RTT. Interestingly, we found a significant variability in the timing and progression of symptom onset among Mecp2-het females, with individuals classified as either early- or late-symptomatic based on the emergence of hallmark neurological features such as clasping and gait abnormalities. This variability pinpoints the heterogeneity of the disease model and highlights the need to stratify Mecp2-het females by symptom onset in future studies to account for the diverse trajectories of disease progression. Additionally, our results reveal a shift from presymptomatic hypersensitivity in the von Frey test to apparent hyposensitivity, intricately linked with the onset of motor symptoms. Further, we found decreased neuronal activation in 6-month-old Mecp2-het females after the hot plate test in the periaqueductal grey, as measured by cFos expression, which does not happen with younger presymptomatic Mecp2-het females. Similarly, there is a lower expression of cannabinoid receptor 1 (CB1) in this area when compared to wild-type siblings. Taken together, our results suggest that both motor impairment and a possible dysregulation of endogenous analgesia might contribute to aberrant sensitivity in Mecp2-het mice. Our study emphasises the presymptomatic phase as crucial for understanding sensory abnormalities in Mecp2-het mice and highlights the challenges in identifying pain in RTT patients. KEY MESSAGES: Mecp2-het mice show early hypersensitivity to stimuli that shifts with age. Classification ofMecp2-het mice by symptom onset shows phenotypic variety. Mecp2-het mice show lower PAG activity when facing a thermal stimulus. Mecp2-het mice show decreased activity and CB1 receptor levels in the PAG.

A randomized double blind placebo controlled study to assess the efficacy of fundal block analgesia during radiofrequency endometrial ablation.

BackgroundChronic pain may involve both nociceptive pain driven by peripheral tissue damage and nociplastic pain reflecting central nervous system dysregulation, as in fibromyalgia. Electroacupuncture has been shown to modulate these pathways, but the underlying brain mechanisms remain unclear. This study investigated how electroacupuncture influences nociceptive-initiated and centrally maintained pain via changes in brain activation and functional connectivity.Methods:In this randomized controlled trial (NCT02064296), female adults with fibromyalgia received either electroacupuncture (n = 19) or sham treatment with inactive laser stimulation (n = 25) over four weeks. Changes in brain activation and connectivity during evoked pressure-pain stimulation were assessed using functional magnetic resonance imaging before and after treatment. Here, we present a secondary analysis of data from the trial. Clinical outcomes assessed include pressure-pain tolerance and widespread pain, and analyses tested whether brain measures mediated treatment-related effects.Results:Here we show that in the electroacupuncture group, reductions in widespread pain are associated with increases in pressure-pain tolerance. This relationship is mediated by greater activation of the primary somatosensory cortex and stronger connectivity between somatosensory and insular regions, consistent with a bottom-up mechanism linking peripheral nociceptive-initiated input to central nociplastic pain modulation. In contrast, the sham group shows reductions in widespread pain linked to decreased precuneus activity and precuneus–insula connectivity, consistent with a top-down process.ConclusionsElectroacupuncture and sham treatments engage distinct neural pathways to influence pain perception. These findings highlight that electroacupuncture modulates nociceptive-initiated and nociplastic pain through a bottom-up sensory pathway, whereas sham treatment engages top-down control. This mechanistic dissociation may inform patient selection and optimization of acupuncture-based therapies for chronic pain.

Peptides for pain sensation and peptides for pain relief: Fighting fire with fire.

Racism is an independent determinant of health and can occur in subtle forms within maternity care. In German-speaking countries, there is a lack of systematic research that considers racism as an explanatory category.To explore how midwifery students perceive, interpret, and discuss racist behavior during their internships in Austrian delivery rooms and to derive implications for midwifery education.A qualitative, exploratory design was applied, using nine problem-centered individual interviews with students in the 4th and 6th semesters at three Austrian universities of applied sciences. Data were analyzed thematically.All participants reported racist incidents, mostly subtle and structurally embedded. Manifestations included stereotypical attributions regarding pain perception, birthing ability, or hygiene; derogatory communication; lack of informed consent; coercive practices; and disadvantages related to language barriers. Students reported feelings of powerlessness within the hierarchical clinical system and emotional strain. A systematic, critical engagement with racism is currently absent from the curriculum.The findings highlight an urgent need for structural changes in both education and practice to promote health equity and break discriminatory patterns of care.

Animal-assisted interventions (AAI) are increasingly recognized as nonpharmacological adjuncts to intensive care medicine. The aim of this paper by the German Society of Internal Intensive Care and Emergency Medicine (DGIIN) is to summarize the scientific rationale, safety considerations, and implementation recommendations for the use of AAI in intensive care units. Therapeutic effects are attributed to neuroendocrine mechanisms, particularly activation of the oxytocin system and reduction of cortisol levels, which can alleviate anxiety, pain perception, and psychological stress in critically ill patients. Early studies have reported significant reductions in anxiety without an associated increase in nosocomial infections. However, clinical implementation requires well-defined structural, hygienic, and ethical frameworks, including standardized risk analyses, binding hygiene and animal welfare standards, and multiprofessional collaboration integrating intensive care, nursing, infection control, and animal therapy. This paper presents the first systematic recommendations in Germany for the safe and quality-assured integration of animal-assisted interventions into intensive care practice and calls for scientifically accompanied implementation focusing on patient safety, animal welfare, and team well-being.

Poly-D,L-lactic acid (PDLLA) skin boosters are widely used for biostimulatory skin rejuvenation, but comparative data on pain perception between injection techniques remain limited. To compare patient-reported pain between intradermal and subdermal PDLLA injections using a randomized, double-blinded, split-injection design. Twenty-one healthy participants (aged 27-64) each received ten facial injections: five intradermal and five subdermal, administered in randomized order using a 32G needle. Pain was assessed using a Visual Analogue Scale (VAS) immediately after each injection. The primary outcome was the difference in mean VAS scores between techniques. Secondary analyses examined the effects of age and gender on pain perception. The mean VAS score for intradermal injections was significantly higher than for subdermal injections (6.18 vs. 3.85, p<0.001). No significant gender-based differences were observed. Patients under 40 reported higher intradermal pain than older subjects (p=0.04), but age had no impact on subdermal pain. Subdermal PDLLA injections are significantly less painful than intradermal injections, likely due to lower nerve density and reduced dermal resistance. With equivalent efficacy and minimal downtime, subdermal injection may be preferable for patient comfort and compliance. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Objective: This is the first population-based study to separately examine whether preventive and treatment dental visits modify the association between stressful life events and toothache. Psychological stress may alter health-seeking behaviors and pain perception, potentially leading to symptom-driven rather than preventive dental visits. Methods: Cross-sectional data were obtained and analyzed from the 2019 wave of the Japan Gerontological Evaluation Study (JAGES), including 19,314 community-dwelling adults aged 65 years and older. Poisson regression analyses were conducted to examine the associations between stressful life events, dental visit history, and self-reported toothache. Results: Higher stressful life events were associated with greater toothache prevalence (PR = 1.189; 95% CI: 1.117–1.264). Preventive dental visits within the past six months were linked to the lowest risk, whereas recent treatment visits were associated with higher risk. Conclusion: Promoting regular preventive dental visits, particularly among individuals under high stress, may help reduce the likelihood of experiencing toothache among older adults.