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ETHNOPHARMACOLOGICAL RELEVANCE: The traditional use of plants for medicinal purposes, called phytomedicine, has been known to provide relief from pain. In Bangladesh, the Chakma indigenous community has been using Allophylus villosus and Mycetia sinensis to treat various types of pain and inflammation. AIM OF THE STUDY: The object of this research is to evaluate the effectiveness of these plants in relieving pain and their antioxidant properties using various approaches such as in vitro, in vivo, and computational techniques. Additionally, the investigation will also analyse the phytochemicals present in these plants. MATERIALS AND METHODS: We conducted in vivo analgesic experiment on Swiss albino mice and in-silico inhibitory activities on COX-2 & 15-LOX-2 enzymes. Assessment of DPPH, Anti Radical Activities (ARA), FRAP, H2O2 Free Radical Scavenging, Reducing the power of both plants performed significant % inhibition with tolerable IC50. Qualitative screening of functional groups of phytochemicals was précised by FTIR and GC-MS analysis demonstrated phytochemical investigations. RESULTS: The ethyl acetate (EtOAc) fractioned Mycetia sinensis extract as well as the ethanoic extract and all fractioned extracts of Allophylus villosus have reported a significant percentage (%) of writhing inhibition (p < 0.05) with the concentrated doses 250 mg as well as 500 mg among the Swiss albino mice for writhing observation of analgesic effect. In the silico observation, a molecular-docking investigation has performed according to GC-MS generated 43 phyto-compounds of both plants to screen their binding affinity by targeting COX-2 and 15-LOX-2 enzymes. Consequently, in order to assess and ascertain the effectiveness of the sorted phytocompounds, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) investigation, DFT (Density-functional theory) by QM (Quantum mechanics), and MDS (Molecular dynamics simulation) were carried out. As the outcome, compounds like 5-(2,4-ditert-butylphenoxy)-5-oxopentanoic acid; 2,4-ditert-butylphenyl 5-hydroxypentanoate; 3,3-diphenyl-5-methyl-3H-pyrazole; 2-O-(6-methylheptan-2-yl) 1-O-octyl benzene-1,2-dicarboxylate and dioctan-3-yl benzene-1,2-dicarboxylate derived from the ethnic plant A. villosus and another ethnic plant M. sinensis extracts enchants magnificent analgesic inhibitions and performed more significant drug like activities with the targeted enzymes. CONCLUSIONS: Phytocompounds from A. villosus & M. sinensis exhibited potential antagonist activity against human 15-lipoxygenase-2 and cyclooxygenase-2 proteins. The effective ester compounds from these plants performed more potential anti-nociceptive activity which could be used as a drug in future.

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BACKGROUND: Venipuncture is one of the most commonly performed medical procedures in paediatric care, but it can also be one of the most painful and distressing experiences for patients. Finding effective strategies to manage pain and fear associated with venipuncture is crucial for improving the paediatric patient experience and promoting positive health outcomes. This study aimed to evaluate the efficacy of a combined approach using a topical analgesic cream (TKTX cream) and a distraction technique (Trace Image and Colouring for Kids-Book, TICK-B) in reducing pain intensity and fear levels in children undergoing venipuncture procedures. METHODS: We conducted this randomised controlled trial among 176 children aged 6-12 years undergoing venipuncture. Participants were randomly assigned to four groups: TICK-B, TKTX cream, TICK-B+TKTX cream and a control group. Pain and fear were measured using the Wong-Baker FACES Pain Rating Scale and Children's Fear Scale. The study was carried out from 20 February 2024 to 1 June 2024 at the emergency unit of Heevi paediatric teaching hospital in the Kurdistan region of Iraq. In the intervention groups, TICK-B was applied for 2-3 min before needle insertion, and TKTX cream was applied 20 min before the venipuncture procedure. All outcome measures were evaluated 2-3 min after the completion of the venipuncture procedure. RESULTS: The combined TICK-B (colouring book) and TKTX cream (topical anaesthetic) intervention was the most effective in reducing both pain intensity (mean score 2.80 vs 7.24 in the control, p<0.001) and fear levels (mean score 0.93 vs 2.83 in the control, p<0.001) during and after venipuncture procedures compared with individual interventions and control. CONCLUSIONS: The combined TICK-B distraction and TKTX cream topical anaesthetic intervention was the most effective in reducing pain intensity and fear during and after venipuncture in children, providing a practical strategy for healthcare providers to optimise needle procedure management. TRIAL REGISTRATION NUMBER: NCT06326125.

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Definitions of human pain acknowledge at least two dimensions of pain, affective and sensory, described as separable and thus potentially differentially modifiable. Using electroencephalography, we investigated perceptual and neural changes of emotional pain modulation in healthy individuals. Painful electrical stimuli were applied after presentation of priming emotional pictures (negative, neutral, positive) and followed by pain intensity and unpleasantness ratings. We found that perceptual and neural event-related potential responses to painful stimulation were significantly modulated by emotional valence. Specifically, pain unpleasantness but not pain intensity ratings were increased when pain was preceded by negative compared to neutral or positive pictures. Amplitudes of N2 were higher when pain was preceded by neutral compared to negative and positive pictures, and P2 amplitudes were higher for negative compared to neutral and positive pictures. In addition, a hierarchical regression analysis revealed that P2 alone and not N2, predicted pain perception. Finally, source analysis showed the anterior cingulate cortex and the thalamus as main spatial clusters accounting for the neural changes in pain processing. These findings provide evidence for a separation of the sensory and affective dimensions of pain and open new perspectives for mechanisms of pain modulation.

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In a randomized, controlled study, whole-body electromyostimulation (WB-EMS) was investigated as a promising alternative treatment technique compared to conventional strength training for the management of knee osteoarthritis (OA). Seventy-two overweight participants with symptomatic knee OA were randomly assigned to WB-EMS (n = 36) or a usual care group (UCG, n = 36). For seven months, the WB-EMS group received three times per fortnight a WB-EMS training, while the UCG was prescribed six-times physiotherapeutic treatments. We observed significant effects for the primary outcome "pain", as determined by the Knee injury and Osteoarthritis Outcome Score (KOOS), with more favourable changes in the WB-EMS group vs UCG (between-group difference 9.0 points, 95%CI 2.9-15.1, p = 0.004). Secondary outcomes, including the other KOOS subscales (symptoms, function in daily living, function in sports/recreational activities and quality of life), 7 day pain diary, hip/leg extensor strength and lower limb function (30s sit-to-stand test), were also statistically significant in favour of the WB-EMS group. Overall, WB-EMS was found to be effective in relieving knee pain symptoms and improving physical function in individuals with symptomatic knee OA compared to usual care treatment. WB-EMS could be used as an alternative therapy in the management of knee OA; particularly for patients that cannot be motivated for conventional training.

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BACKGROUND: The use of self-report pain scales in persons with aphasia can be challenging due to communication and cognitive problems, while for assessing pain self-report pain is considered the gold standard (Harrison RA, Field TS. Post stroke pain: identification, assessment, and therapy. Cerebrovasc Dis. 2015;39(3-4):190-201.). An observational scale may be used as an alternative. This study examines the validity and reliability of the observational Pain Assessment in Impaired Cognition (PAIC15) scale in persons with aphasia. METHODS: Persons with aphasia were observed during rest and transfer by two observers using the PAIC15. The PAIC15 comprises 15 items covering the three domains of facial expressions, body movements, and vocalizations. When able, the participant completed four self-report pain scales after each observation. The observations were repeated within one week. For criterion validity, correlations between the PAIC15 and self-report pain scales were calculated and for construct validity, three hypotheses were tested. Reliability was determined by assessing internal consistency, and intra- and interobserver agreement. RESULTS: PAIC15 observations were obtained for 71 persons (mean age 75.5 years) with aphasia. Fair positive correlations (rest: 0.35-0.50; transfer: 0.38-0.43) were reported between PAIC15 and almost all self-report pain scales. Results show that significantly more pain was observed in persons with aphasia during transfer than during rest. No differences were found for observed pain between persons with aphasia who use pain medication and those without, or persons who have joint diseases compared to those without. Results showed acceptable internal consistency. Intra- and interobserver agreement was high for most PAIC15 items, particularly for the domains body movements and vocalizations during rest and transfer. CONCLUSIONS: Recognition of pain in persons aphasia using the PAIC15 showed mixed yet promising results.

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OBJECTIVE: To examine the relationship between C-reactive protein (CRP) and knee pain, and further explore whether this association is mediated by obesity. METHODS: The population was derived from 1999 to 2004 National Health and Nutrition Examination Survey. Logistic regression was used to analyze the relationship between CRP and knee pain in three different models, and the linear trend was analyzed. A restricted cubic spline model to assess the nonlinear dose-response relationship between CRP and knee pain. Mediation analyses were used to assess the potential mediating role of obesity. Subgroup analyses and sensitivity analyses were performed to ensure robustness. RESULTS: Compared with adults with lower CRP (first quartile), those with higher CRP had higher risks of knee pain (odds ratio 1.39, 95% confidence interval 1.12-1.72 in third quartile; 1.56, 1.25-1.95 in fourth quartile) after adjusting for covariates (except body mass index [BMI]), and the proportion mediated by BMI was 76.10% (p < .001). BMI and CRP were linear dose-response correlated with knee pain. The odds ratio for those with obesity compared with normal to knee pain was 2.27 (1.42-3.65) in the first quartile of CRP, 1.99 (1.38-2.86) in the second, 2.15 (1.38-3.33) in the third, and 2.92 (1.72-4.97) in the fourth. CONCLUSION: Obesity mediated the systemic inflammation results in knee pain in US adults. Moreover, higher BMI was associated with higher knee pain risk in different degree CRP subgroups, supporting an important role of weight loss in reducing knee pain caused by systemic inflammation.

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The painful hip has been a topic of study that has evolved from the beginning of the last century to the present. The clinical approach is complex, and requires a systematization process associated with good questioning, clinical maneuvers with their corresponding interpretation, and complementary imaging studies. The understanding of hip pathology, especially in young adults, is highly simplified and sometimes underdiagnosed, therefore, not treated in a timely manner. The prevalence of painful hip is more common in males (49 to 55%) than in females (25 to 28%), and the causes may vary according to demographic characteristics and the history of each patient. Bryan Kelly, made a topographic and anatomical description of the approach to the painful hip according to the theory or system of the layers: I. Osteochondral layer; II. Inert layer; III. Contractile layer; and IV. Neuro-mechanical layer. This system helps us understand the anatomical site of pain and its clinicopathological correlation. The semiological approach to hip pain is the fundamental pillar for differential diagnosis. We can divide it according to its topography into anterior, lateral and posterior, as well as according to its chronology and characteristics. The physical examination should be carried out systematically, starting from a generalized inspection of gait and posture to the evaluation of specific signs for alterations in each layer, which evoke pain with specific postures and ranges of mobility, or weakness and alterations in the arc of mobility of the joint. Image evaluation is initially recommended with radiographic projections that evaluate different planes, both coronal, sagittal and axial, complemented with panoramic views, and eventually dynamic sagittal ones if necessary. Requesting specific studies such as tomography to evaluate bone structure and reserve, or simple MRI when there is suspicion of soft tissue affection, or failing that, arthroresonance for joint pathology, will depend on the clinical symptoms and radiographic findings.

La cadera dolorosa ha sido un tema de estudio que ha evolucionado desde principios del siglo pasado hasta la actualidad. El abordaje clínico es complejo y exige un proceso de sistematización asociado a un buen interrogatorio, maniobras clínicas con su interpretación correspondiente y estudios de imagen complementarios. El entendimiento de la patología de cadera, sobre todo en adulto joven, es altamente simplificado y en ocasiones infradiagnosticado, por lo tanto, no tratado en tiempo y forma. La prevalencia de cadera dolorosa es más frecuente en el sexo masculino (49 a 55%) que en el femenino (25 a 28%), y las causas pueden variar de acuerdo a características demográficas y a los antecedentes de cada paciente. Bryan Kelly realizó una descripción topográfica y anatómica del abordaje de la cadera dolorosa de acuerdo con la teoría o sistema de las capas: I. Capa osteocondral; II. Capa inerte; III. Capa contráctil; y IV. Capa neuromecánica. Este sistema nos ayuda a entender el sitio anatómico del dolor y su correlación clínico-patológica. El abordaje semiológico del dolor de cadera es el pilar fundamental para el diagnóstico diferencial. Podemos dividirlo de acuerdo con su topografía en anterior, lateral y posterior, así como de acuerdo a su cronología y características. La exploración física debe realizarse de manera sistemática, iniciando desde inspección generalizada, de la marcha y postura hasta la evaluación de signos específicos para alteraciones en cada capa, los cuales evocan dolor con posturas y arcos de movilidad específicos, o bien debilidad y alteraciones en el arco de movilidad de la articulación. La evaluación por imagen se recomienda inicialmente con proyecciones radiográficas que evaluen diferentes planos, tanto coronal, sagital y axial, complementado con panorámicas, y eventualmente sagitales dinámicas de ser necesarios. Solicitar estudios específicos como tomografía para evaluar estructura y reserva ósea, o bien, resonancia simple cuando hay sospecha de afección a tejidos blandos, o en su defecto, artrorresonancia para patología articular, dependerá de la clínica y los hallazgos radiográficos.

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AIM: Pain and anxiety levels in palliative care patients negatively impact their quality of life, highlighting the need for research on non-pharmacological methods. This study aimed to evaluate the effects of music and aromatherapy interventions on pain, anxiety, and stress levels in these patients. MATERIAL AND METHODS: The research was designed as a single-blind, four-group, randomized controlled trial. The sample consisted of 88 patients hospitalized in a palliative care center (receiving palliative care services with terminal or advanced diseases). Patients were randomly assigned to four groups (n = 22, music, aromatherapy, music and aromatherapy, and control group). Patients in the experimental groups received the intervention to which they were assigned for 20 min each day for three consecutive days: music, aromatherapy, or music accompanied by aromatherapy. No intervention was applied to the control group. The patients' levels of pain, anxiety, and stress were assessed before and after the intervention using the Visual Analog Scale (VAS), the Facial Anxiety Scale (FAS), and the Distress Thermometer. RESULTS: No significant differences were found in the demographic characteristics of the groups (p > 0.05). The Wilcoxon Signed-Rank and Kruskal-Wallis tests indicated statistically significant differences in pre- and post-intervention scores for VAS, FAS, and Distress across all experimental groups on all follow-up days (p < 0.05). CONCLUSION: Implementing music, aromatherapy, and their combination effectively reduced pain, anxiety, and stress levels in palliative care patients, suggesting these non-pharmacological interventions can improve their quality of life. TRIAL REGISTRATION: ClinicalTrails.gov (Registration number: NCT06024954) at 05-SEP-2024.

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Background: Posttraumatic stress disorder and medically unexplained pain frequently co-occur. While pain is common during traumatic events, the processing of pain during trauma and its relation to audiovisual and pain intrusions is poorly understood.Objective: Here we investigate neural activations during painful analogue trauma, focusing on areas that have been related to threat and pain processing, and how they predict intrusion formation. We also examine the moderating role of cumulative lifetime adversity.Methods: Sixty-five healthy women were assessed using functional magnetic resonance imaging. An analogue trauma was induced by an adaptation of the trauma-film paradigm extended by painful electrical stimulation in a 2 (film: aversive, neutral) x 2 (pain: pain, no-pain) design, followed by 7-day audiovisual and pain intrusion assessment using event-based ecological momentary assessment. Intrusions were fitted with Bayesian multilevel regression and a hurdle lognormal distribution.Results: Conjunction analysis confirmed a wide network including anterior insula (AI) and dorsal anterior cingulate cortex (dACC) being active both, during aversive films and pain. Pain resulted in activation in areas amongst posterior insula and deactivation in a network around ventromedial prefrontal cortex (VMPFC). Higher AI and dACC activity during aversive>neutral film predicted greater audiovisual intrusion probability over time and predicted greater audiovisual intrusion frequency particularly for participants with high lifetime adversity. Lower AI, dACC, hippocampus, and VMPFC activity during pain>no-pain predicted greater pain intrusion probability particularly for participants with high lifetime adversity. Weak regulatory VMPFC activation was associated with both increased audiovisual and pain intrusion frequency.Conclusions: Enhanced AI and dACC processing during aversive films, poor pain vs. no-pain discrimination in AI and dACC, as well as weak regulatory VMPFC processing may be driving factors for intrusion formation, particularly in combination with high lifetime adversity. Results shed light on a potential path for the etiology of PTSD and medically unexplained pain.

AI and dACC play a common role for both trauma- and pain-processing.In combination with high lifetime adversity, higher AI and dACC aversive film processing was associated with higher audiovisual intrusion frequency, whereas weaker AI and dACC pain discrimination enhanced the chance for pain intrusions.Weak regulatory VMPFC activity in aversive situations increased both audiovisual and pain intrusion formation.

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Varicocele is a prevalent vascular disorder affecting the male reproductive system, leading to scrotal pain and testicular dysfunction. Epidemiological studies have shown that varicocele occurs in approximately 10% to 15% of adult males, while scrotal pain affects 2% to 10% of the population. Currently, clinical treatment options for varicocele-induced scrotal pain include general therapy, medication, and surgery. Among these, surgical intervention is considered the most effective method, boasting a success rate of 80%. However, it carries risks such as postoperative bleeding, infection, and recurrence, making it less desirable for some patients. In recent years, transcutaneous neuromuscular electrical stimulation has gained wide acceptance for treating various andrological conditions, including erectile dysfunction and premature ejaculation, yielding positive outcomes. This non-invasive technique offers a promising alternative for managing varicocele-induced scrotal pain, potentially reducing the need for surgical intervention and its associated risks. Its growing popularity underscores the need for further research and clinical trials to validate its efficacy and safety in treating this condition.

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The brain integrates information from pain-predictive cues and noxious inputs to construct the pain experience. Although previous studies have identified neural encodings of individual pain components, how they are integrated remains elusive. Here, using a cue-induced pain task, we examined temporal functional magnetic resonance imaging activities within the state space, where axes represent individual voxel activities. By analyzing the features of these activities at the large-scale network level, we demonstrated that overall brain networks preserve both cue and stimulus information in their respective subspaces within the state space. However, only higher-order brain networks, including limbic and default mode networks, could reconstruct the pattern of participants' reported pain by linear summation of subspace activities, providing evidence for the integration of cue and stimulus information. These results suggest a hierarchical organization of the brain for processing pain components and elucidate the mechanism for their integration underlying our pain perception.

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Background: Insufficiently managed incisional (INC) pain severely affects patients' life quality and rehabilitation after a major operation. However, mechanisms underlying INC pain still remain poorly understood. Methods: A mouse model of INC pain was established by skin plus deep muscle incision. Biochemistry assay, in vivo reactive oxygen species (ROS) imaging, Ca2+ imaging combined with retrograde labelling, neuron tracing and nocifensive behavior test, etc. were utilized for mechanism investigation. Results: We found pro-nociceptive cytokine interleukin -33 (IL-33) ranked among top up-regulated cytokines in incised tissues of INC pain model mice. IL-33 was predominantly expressed in keratinocytes around the incisional area. Neutralization of IL-33 or its receptor suppression of tumorigenicity 2 protein (ST2) or genetic deletion of St2 gene (St2 -/-) remarkably ameliorated mechanical allodynia and improved gait impairments of model mice. IL-33 contributes to INC pain by recruiting macrophages, which subsequently release ROS in incised tissues via ST2-dependent mechanism. Transfer of excessive macrophages enhanced oxidative injury and reproduced mechanical allodynia in St2 -/- mice upon tissue incision. Overproduced ROS subsequently activated functionally up-regulated transient receptor potential ankyrin subtype-1 (TRPA1) channel innervating the incisional site to produce mechanical allodynia. Neither deleting St2 nor attenuating ROS affected wound healing of model mice. Conclusions: Our work uncovered a previously unrecognized contribution of IL-33/ST2 signaling in mediating mechanical allodynia and gait impairment of a mouse model of INC pain. Targeting IL-33/ST2 signaling could be a novel therapeutic approach for INC pain management.

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Osgood Schlatter's disease (OSD) is characterized by pain at the tibial tuberosity provoked during knee-loading activities, and is common in adolescent athletes. The aim of this study was to characterize clinical, pain and ultrasound imaging characteristics in participants with OSD compared to controls. This cross-sectional study included adolescents diagnosed with OSD and matched controls. Following baseline evaluation including ultrasound, participants completed the following aggravating activities in a randomized order: single-leg isometric knee hold, single-leg squat, single-leg vertical jump, hopping, running, cutting, lunges, and walking. Participants rated pain intensity on a numeric rating scale (0-10; no pain to worst pain imaginable) and localization during activities. We included 35 participants with OSD (48.5% females, age 13.0 [SD 1.5]) and 21 controls (47.6% females, age 13.4 [SD1.4]). Doppler signal was more prevalent in OSD participants at the tendon (77% vs. 30%) and tuberosity (29% vs. 10%). Tendon thickness was greater in OSD at distal (mean difference = 4.5 mm 95% CI 1.5-7.5) and proximal sites (mean difference = 4.2 95% CI 0.1-8.3). Aggravating activities induced higher pain in OSD. The greatest differences between OSD and control were the dynamic single-leg squat (mean difference = 4.2 (95% CI 3.22-5.1)). Pain was localized at the tibial tuberosity and patellar tendon during activities. Sex, sports participation, bilateral pain, and Doppler were associated with greater pain during aggravating activities. Single-leg activities loading the tibial tuberosity through the tendon appear to provoke OSD-related pain more than other sports specific movements. This may be useful to guide adolescents on which activities are likely to aggravate pain.

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BACKGROUND: Electroencephalography (EEG) is a promising tool for identifying the physiological biomarkers of fibromyalgia (FM). Evidence suggests differences in power band and density between individuals with FM and healthy controls. EEG changes appear to be associated with pain intensity; however, their relationship with the quality of pain has not been examined. We aimed to investigate whether abnormal EEG in the frontal and central points of the 10-20 EEG system in individuals with FM is associated with pain's sensory-discriminative and affective-motivational dimensions. The association between EEG and the two dimensions of emotional disorders (depression and anxiety) was also investigated. METHODS: In this cross-sectional pilot study, pain experience (pain rating index [PRI]) and two dimensions of emotional disorders (depression and anxiety) were assessed using the McGill Pain Questionnaire (PRI-sensory and PRI-affective) and Hospital Anxiety and Depression Scale (HADS), respectively. In quantitative EEG analysis, the relative spectral power of each frequency band (delta, theta, alpha, and beta) was identified in the frontal and central points during rest. RESULTS: A negative correlation was found between the relative spectral power for the delta bands in the frontal (r= -0.656; p = 0.028) and central points (r= -0.624; p = 0.040) and the PRI-affective scores. A positive correlation was found between the alpha bands in the frontal (r = 0.642; p = 0.033) and central points (r = 0.642; p = 0.033) and the PRI-affective scores. A negative correlation between the delta bands in the central points and the anxiety subscale of the HADS (r = -0.648; p = 0.031) was detected. CONCLUSION: The affective-motivational dimension of pain and mood disorders may be related to abnormal patterns of electrical activity in patients with FM. TRIAL REGISTRATION: Retrospectively registered on ClinicalTrials.gov (NCT05962658).

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