Estudio comparativo del dolor abdominal en las culturas maya Tzeltal, maya Tzotzil y maya Q ́eqchi ́y el uso de Ageratina ligustrina para su tratamiento / Comparative study of abdominal pain in the Mayan cultures Tzeltal, Maya Tzotzil and Maya Q ́eqchi´ and use of Ageratina ligustrina for the treatment

El presente estudio es una comparación del dolor abdominal producido por trastornos gastrointestinales, aliviado por Ageratina ligustrina , entre los grupos maya Tzeltal, Tzotzil y Q ́eqchi ́, el cual integró un enfoque etnomédico, etnobotánico y transcultural, comparando estudios previos con el presente trabajo de campo. Para evaluar la eficacia de Ageratina para aliviar el dolor abdominal, se realizó un inventario de las moléculas reportadas en esta especie, así como de su actividad farmacológica, a través de una revisión bibliográfica. Los resultados mostraron que la epidemiología del dolor producido por TGI, su etnobotánica y el modelo explicativo del dolor abdominal fueron similares entre grupos étnicos. Asimismo, se identificaron 27 moléculas con efectos antiinflamatorios y antinociceptivos, lo que podría explicar por qué esta especie es culturalmente importante para los pobladores maya Tzeltal, Tzotzil y Q ́eqch i ́ para el alivio del dolor abdominal, mientras que, desde el punto de vista biomédico, es una especie con potencial para inhibir el dolor visceral.

The current study is a comparison of the abdominal pain conception produced by gastrointestinal disorders, relieved by Ageratina ligustrina , among inhabitants of the Mayan Tzeltal, Tzotzil, and Q'eqchi' groups ethnomedical, ethnobotanical, and cross -cultural approaches were used to compare previous studies with the present field work. To evaluate the efficacy of A. ligustrina to relieve pain, also through a bibliographic review an inventory of the molecules present in this species was performed, as well as their pharmacological activity. The results showed that the epidemiology of pain produced by GID, its ethnobotany, and the explanatory model of abdominal pain are similar among ethnic groups. Likewise, 27 molecules with anti-inflammatory and anti-nociceptive effects were identified, which could explain why this species is culturally important for the Mayan Tzeltal, Tzotzil, and Q'eqchi' groups for the relief of abdominal pain, while, from a biomedical point of view, it is a species with potential to inhibit visceral pain.

Validación de test de flexión-relajación para definir un déficit lumbar con electrodos tetrapolares / Validation of the flexion-relaxation test to define a lumbar deficit with tetrapolar electrodes

Introducción y objetivo: Obtener un nuevo punto de corte (PC) para un test de flexión-relajación (FR) lumbar efectuado con electrodos (e.) tetrapolares, desde valores ya definidos con dispositivos bipolares.Materiales y métodosLa muestra del estudio consta de 47 pacientes en situación de incapacidad temporal por dolor lumbar (DL). Fueron evaluados mediante un test de dinamometría isométrica, una prueba cinemática y una valoración del fenómeno FR.Se plantean dos experimentos con curvas ROC. El primero, con 47 pacientes que efectuaron de modo consecutivo el test FR con ambos tipos de electrodos, utilizándose como variable de clasificación el punto de corte conocido para los e. bipolares (2,49uV). En el segundo, con los datos de la EMGs registrados con e. tetrapolares en 17 pacientes, se efectúa un test de DeLong que compara las 2 curvas ROC que construimos, por un lado, al clasificar la muestra desde pruebas de dinamometría y cinemática, y por el otro, al clasificarlos con los valores de la EMGs bipolar.ResultadosUn total de 34 pacientes completaron adecuadamente las valoraciones del primer experimento y 17 pacientes el segundo. El primer estudio arroja un punto de corte de 1,2uV, con un AUC del 87,7%; sensibilidad 84,2% y especificidad 80%. El segundo muestra un PC para los e. bipolares de 1,21uV (AUC 87,5%) y para los e. tetrapolares de 1,43 (AUC 82,5%) con un test de DeLong sin diferencias significativas entre ambas curvas (p>0,4065).ConclusionesLa metodología de validación con curvas ROC ha permitido obtener un nuevo PC para la prueba FR de modo práctico, simplemente simultaneando ambos test sobre el mismo grupo de pacientes hasta obtener una muestra significativa. (AU)

Introduction and objective: To obtain a new cut-off point (CP) for a lumbar flexion-relaxation (RF) test established with tetrapolar (e.) electrodes, from values already defined with bipolar devices.Materials and methodsThe study sample consists of 47 patients in a situation of temporary disability due to low back pain (DL). They were evaluated by means of an isometric dynamometry test, a kinematic test and an assessment of the FR phenomenon.Two experiments with ROC curves are proposed. The first, with 47 patients who consecutively performed the RF test with both types of electrodes, using the cut-off point (CP) known for the e. bipolar (2.49μV). In the second, with the EMG data recorded with e. tetrapolar in 17 patients, a DeLong test was performed that compares the 2 ROC curves that were constructed on the one hand, by classifying the sample from dynamometry and kinematic tests, and on the other, by classifying them with the bipolar EMG values.ResultsA total of 34 patients adequately completed the evaluations of the first experiment and 17 patients the second. The first study shows a cut-off point of 1.2μV, with an AUC of 87.7%; Sensitivity 84.2% and Specificity 80%. The second shows a PC for e. bipolars of 1.21μV (AUC 87.5%) and for e. tetrapolar values of 1.43 (AUC 82.5%) with a DeLong test without significant differences between both curves (p>0.4065).ConclusionsThe validation methodology with ROC curves has made it possible to obtain a new PC for the RF test in a practical way, simply by simultaneously performing both tests on the same group of patients until a significant sample is obtained. (AU)

The effect of commuting time on burnout: the mediation effect of musculoskeletal pain.

OBJECTIVES: This study explores the relationship among commuting, musculoskeletal (MS) pain, and burnout. METHODS: An observational and cross-sectional study was conducted at a medical university-affiliated hospital in Taichung, Taiwan in 2021. The two questionnaire was used and they included the Copenhagen Burnout Inventory (CBI) and the Nordic Musculoskeletal Questionnaire (NMQ). All participants were invited to complete the cross-sectional survey. A multiple linear regression was assessed correlations between commuting, MS pain, and burnout. RESULTS: After excluding those with missing data, 1,615 healthcare workers were deemed valid as research participants. In multiple linear regression, commuting time longer than 50 min was associated with personal burnout (PB) in the presence of adjusted confounders; however, long commuting time was not associated with work-related burnout (WB). Furthermore, the choice of commuting method did not affect PB or WB. Notably, both neck and shoulder pain (NBSP) and ankle pain (BAP) increase the risk of PB and WB. The mediation analysis demonstrated that NBSP is a mediating factor, increasing the level of PB and WB for commuting times longer than 50 min. CONCLUSIONS: Healthcare workers who commute for more than 50 min should be considered part of a high-risk group for burnout and musculoskeletal pain. They should also be provided with resources and programs focused on burnout prevention and MS pain relief.

Barodontalgia during hyperbaric oxygen therapy of an 8-year-old male: A case report.

Barodontalgia, barometric pressure-induced dental pain, may occur during hyperbaric oxygen(HBO2) therapy due to pressure changes. This case report presents an 8-year-old male patient with barodontalgia. The patient declared a severe toothache during HBO2 therapy. The diving medicine specialist referred the patient to the dental clinician immediately. On clinical examination, the pain was thought to be caused by caries lesions of the deciduous teeth in the left maxillary molar region. Tooth extraction was suggested. After extraction, the patient continued hyperbaric oxygen therapy sessions without any pain. The patient was recommended for an intraoral and radiographic examination session one week after the extraction. In conclusion, caries lesions and faulty restorations should be examined before hyperbaric oxygen therapy sessions. Even though barodontalgia is a rare phenomenon, dental examination is essential to avoid these kinds of pain-related complications. All carious lesions and defective restorations must be treated, if necessary. Removal of faulty restorations and management of inflammation as part of the treatment is suggested before exposure to pressure changes.

Clinical Outcome for Lumbar Disc Herniation Treatment with Intradiscal Oxygen-ozone Therapy.

BACKGROUND: Low back pain due to disc herniation is a common problem causing frequent hospital visits and loss of working days with major socio-economic impact. Conservative treatments like analgesics, physiotherapy do not work in all patients. Surgical treatment has been the mainstay of treatment when indicated but is associated with anesthetic and surgical complications. Intradiscal oxygen-ozone chemonucleolysis is a minimally invasive procedure done under local anesthesia and has promising role in shrinking the bulged disc and reducing nerve root compression and related symptoms. This retrospective study was done to see how intradiscal oxygen-ozone chemonucleolysis reduces pain severity in patients with discogenic low back pain. METHODS: Retrospective data were retrieved of those patients who underwent fluoroscopy guided intradiscal oxygen-ozone chemonucleolysis with 5-6 ml of an O2-O3 mixture (concentration of 30 microgram/ml) during a period of two years in Nepal pain care and research center. Numerical pain scale (NRS) at various follow ups were compared to preprocedural NRS. RESULTS: Preprocedural NRS was 8± 13. NRS at three hours, one week, one month, three months and six months were 2± 13 (73 percent reduction), 2± 53 (68 percent reduction), 2± 27 (72 percent reduction), 1± 08 (77 percent reduction) and 1± 67 (79 percent reduction) respectively. CONCLUSIONS: Intradiscal oxygen-ozone chemonucleolysis can be a useful modality of treatment for discogenic low back pain in patients who fail to respond to conservative management and in whom surgery is not indicated.

Cruciate-Retaining Total Knee Arthroplasty versus Unicompartmental Knee Arthroplasty in Medial Compartmental Osteoarthritis: A Propensity Score-Matched Analysis of Early Postoperative Recovery.

Background: Cruciate-retaining (CR) total knee arthroplasty (TKA) may provide better physiological knee kinematics, proprioception, and quadricep recovery than posterior-stabilized (PS) TKA. Therefore, we hypothesized that CR TKA with multimodal pain control may provide comparable postoperative pain and recovery as unicompartmental knee arthroplasty (UKA). Methods: This study included patients with isolated medial compartment knee osteoarthritis who underwent CR TKA and UKA. TKA and UKA patients were propensity score-matched with age and body mass index (BMI) and compared using visual analog scales (VAS) for pain scores, total amount of morphine use (TMU), knee flexion angle, straight leg raise (SLR), independent ambulation, length of hospital stay (LOS), and costs during hospitalization. Results: After propensity score matching, 46 patients were included in the TKA and UKA groups, respectively, with no differences in demographic data. VAS at 6-72 h and TMU at 48 h after surgery were comparable between the groups. The knee flexion angle in the UKA group was significantly higher at 24 h (60.0° vs 46.6°; p<0.001) and 48 h (76.9° vs 69.1°; p = 0.021) than that in the TKA group. The SLR in the UKA group was significantly higher than that in the TKA group at 24-72 h. The UKA group ambulated significantly earlier (1.56 vs 2.13 days; p<0.001), had shorter LOS (3.68 vs 4.28 days; p<0.004) and incurred 12.43% lower costs when compared to the TKA group. Conclusion: Patients who underwent CR TKA with multimodal pain management did not experience more postoperative pain or morphine use than those who underwent UKA. However, UKA patients seem to experienced faster recovery and shorter LOS than CR-TKA patients during the early postoperative course. Accordingly, UKA may be considered instead of TKA for patients who are good candidates for UKA and require expedited recovery.

"Navigating chaos": Urban, Rural, and Remote Patient Experiences in Accessing Healthcare with Indigenous and Non-Indigenous Perspectives of Living with Chronic Low Back Pain.

Background: Healthcare access for chronic low back pain is complex and should consider not only the health system, but patient care seeking experiences as well. People who live in rural and remote communities and/or identify as being Indigenous may often encounter additional barriers to accessing care for chronic low back pain; thus, these contexts must be considered to fully understand barriers and facilitators. Aims: The aim of this study was to understand care-seeking experiences of people living with chronic back pain in Saskatchewan and determine unique experiences facing urban, rural, remote, and/or Indigenous peoples. Methods: Thirty-three participants with chronic low back pain completed a preliminary survey followed by individual semistructured interviews. Participants were categorized as urban, rural, or remote including Indigenous status. A qualitative interpretive research approach with inductive thematic analysis was employed. Results: Three overarching themes were identified with the following subthemes: (1) healthcare access challenges: challenges to accessing care, challenges within the health system, and challenges leading to self-directed management/coping strategies; (2) healthcare access facilitators: funded care, participant education and knowledge, patient-provider communication, and care closer to home; and (3) participant recommendations for improved care provision: coordination of care, integrative and holistic care, and patient-centered care and support. Rural and remote participants highlighted travel as a main barrier. Indigenous participant experiences emphasized communication with healthcare providers and past experiences influencing desire to access care. Conclusion: Participants identified a range of challenges and facilitators as well as recommendations for improving access to care for chronic low back pain, with unique barriers for rural, remote, and Indigenous participants.

Contexte: L'accès aux soins de santé pour la lombalgie chronique est complexe et devrait tenir compte non seulement du système de santé, mais aussi des expériences de recherche de soins des patients. Les personnes vivant dans des communautés rurales et éloignées et/ou qui s'identifient comme autochtones font souvent face à des obstacles supplémentaires pour accéder aux soins pour la lombalgie chronique; il faut donc tenir compte de ces contextes pour bien comprendre les obstacles et les facilitateurs.Objectifs: L'objectif de cette étude était de comprendre les expériences de recherche de soins des personnes vivant avec une lombalgie chronique en Saskatchewan et de déterminer les expériences uniques d'accès aux soins auxquelles sont confrontées les personnes vivant en milieu urbain, rural, éloigné et/ou ayant un statut d'autochtone.Méthodes: Trente-trois participants souffrant de lombalgie chronique ont répondu à un questionnaire préliminaire suivi d'entretiens individuels semi-structurés. Les participants ont été catégorisés comme vivant en milieu urbain, rural, éloigné, incluant ceux ayant un statut d'autochtone. Une approche de recherche qualitative interprétative avec une analyse thématique inductive a été utilisée.Résultats: Trois thèmes principaux ont été répertoriés avec les sous-thèmes suivants : (1) difficultés d'accès aux soins de santé : difficultés pour accéder aux soins, difficultés au sein du système de santé et difficultés conduisant à des stratégies de gestion et d'adaptation autonomes; (2) facilitateurs de l'accès aux soins de santé : financement des soins, éducation et connaissances des participants, communication entre le patient et le prestataire de soins et proximité des soins par rapport au domicile et (3) recommandations des participants pour l'amélioration de la prestation des soins : la coordination des soins, les soins intégrés et holistiques, les soins et le soutien centrés sur le patient. Les participants des régions rurales et éloignées ont souligné que les déplacements constituaient un obstacle majeur. Les expériences des participants autochtones ont mis l'accent sur la communication avec les prestataires de soins de santé et les expériences passées qui influencent le désir d'accéder aux soins.Conclusion: Les participants ont répertorié un ensemble de difficultés, de facilitateurs et de recommandations pour améliorer l'accès aux soins pour les lombalgies chroniques, qui présente des obstacles uniques pour les participants vivant en milieu rural et éloigné et les participants autochtones.

Brain-derived neurotrophic factor (BDNF) in chronic pain research: A decade of bibliometric analysis and network visualization.

Chronic pain research, with a specific focus on the brain-derived neurotrophic factor (BDNF), has made impressive progress in the past decade, as evident in the improved research quality and increased publications. To better understand this evolving landscape, a quantitative approach is needed. The main aim of this study is to identify the hotspots and trends of BDNF in chronic pain research. We screened relevant publications from 2013 to 2022 in the Scopus database using specific search subject terms. A total of 401 documents were selected for further analysis. We utilized several tools, including Microsoft Excel, Harzing's Publish or Perish, and VOSViewer, to perform a frequency analysis, citation metrics, and visualization, respectively. Key indicators that were examined included publication growth, keyword analyses, topmost influential articles and journals, networking by countries and co-citation of cited references. Notably, there was a persistent publication growth between 2015 and 2021. "Neuropathic pain" emerged as a prominent keyword in 2018, alongside "microglia" and "depression". The journal Pain® was the most impactful journal that published BDNF and chronic pain research, while the most influential publications came from open-access reviews and original articles. China was the leading contributor, followed by the United States (US), and maintained a leadership position in the total number of publications and collaborations. In conclusion, this study provides a comprehensive list of the most influential publications on BDNF in chronic pain research, thereby aiding in the understanding of academic concerns, research hotspots, and global trends in this specialized field.

A new perspective of frozen shoulder pathology; the interplay between the brain and the immune system.

Frozen shoulder (FS), also known as adhesive capsulitis of the shoulder (FS), is a fibrotic inflammatory process of unknown etiology whose main symptoms are pain, stiffness and the loss of joint mobility. These symptoms may be associated with pathologies such as diabetes, Dupuytren's syndrome and the prevalence of today's sedentary lifestyle. This literature review provides an overview of the epidemiology and pathogenesis of this pathology, as well as the mechanisms of lowgrade chronic inflammation and infection, insulin resistance, and omics-science associated with it. We also propose a new hypothesis related to the possibility that the GABAergic system could play a decisive role in the development of frozen shoulder and that therefore diabetes type 1, endocrinological autoimmune disorders and frozen shoulder are connected by the same pathophysiological mechanisms. If that is true, the combined presence of psycho-emotional stress factors and pathogenic immune challenges could be the main causes of frozen shoulder syndrome. Finally, we propose a series of possible intervention strategies based on a multifactorial etiological and mechanistic concept.

Non-obese lipedema patients show a distinctly altered quantitative sensory testing profile with high diagnostic potential.

Introduction and Objectives: Lipedema is a widespread severe chronic disease affecting mostly women. Characterized by painful bilateral fat accumulation in extremities sparing hands and feet, objective measurement-based diagnosis is currently missing. We tested for characteristic psychometric and/or sensory alterations including pain and for their potential for medical routine diagnosis. Methods: Pain psychometry was assessed using the German Pain Questionnaire. Sensory sensitivity toward painful and nonpainful stimuli was characterized in non-obese lipedema patients and matched controls using the validated quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain. Results: Lipedema patients showed no overt psychometric abnormalities. Pain was reported as somatic rather than psychosomatic aversive. All QST measurements were normal, but the z-score of pressure pain thresholds (PPT) was twofold reduced and the z-score of vibration detection thresholds (VDT) was two and a half times increased. Both thresholds were selectively altered at the affected thigh but not the unaffected hand. Receiver operating characteristic analysis of the combination of PPT and VDT of thigh vs hand into a PVTH score (PPT, VDT, thigh, hand-score) shows high sensitivity and specificity, categorizing correctly 95.8% of the participants as lipedema patients or healthy controls. Bayesian inference analysis corroborated the diagnostic potential of such a combined PVTH score. Conclusion: We propose to assess PPT and VDT at the painful thigh and the pain-free hand. Combination in a PVTH score may allow a convenient lipedema diagnosis early during disease development.

Intraoperative reliability of the tibial anteroposterior axis "Akagi's Line" in total knee arthroplasty.

Purpose: The tibial anatomical anteroposterior (AP) axis "Akagi's line" was originally defined on computed tomography (CT) in total knee arthroplasty (TKA); however, its intraoperative reproducibility remains unknown. This study aimed to evaluate the intraoperative reproducibility of the Akagi's line and its effect on postoperative clinical outcomes. Methods: This prospective study included 171 TKAs. The rotational angle of the intraoperative Akagi's line relative to the original Akagi's line (RAA) defined on CT was measured. The RAA was calculated based on the tibial component rotational angles relative to the intraoperative Akagi's line measured using the navigation system and CT. The effects of RAA on postoperative clinical outcomes and rotational alignments of components were also evaluated. Results: The mean absolute RAA (standard deviation) value was 5.5° (3.9°). The range of RAA was 22° internal rotation to 16° external rotation. Intraoperative Akagi's line outliers (RAA > 10°) were observed in 14% of the knees (24 knees). In outlier analysis, the tibial component rotation angle was externally rotated 6.5° (5.6°) in the outlier group and externally rotated 3.7° (4.2°) in the nonoutlier group (≤10°), with a significant difference between the two groups. Additionally, the outlier group (RAA > 10°) showed lower postoperative clinical outcomes. Conclusion: The original Akagi's line defined on CT showed insufficient reproducibility intraoperatively. The poor intraoperative detection of Akagi's line could be the reason for the tibial component rotational error and worse postoperative clinical outcomes. Level of Evidence: Level IV, case series.

Revealing the mechanism of central pain hypersensitivity in primary dysmenorrhea: evidence from neuroimaging.

Background: Primary dysmenorrhea (PDM) is the most common problem in menstruating women. A number of functional magnetic resonance imaging (fMRI) study have revealed that the brain plays a crucial role in the pathophysiology of PDM. However, these results have been inconsistent, and there is a lack of a comprehensive fMRI study to clarify the onset and long-term effects of PDM. The aim of this study was thus to investigate the onset and long-term effects of PDM in a cohort of patients with PDM. Methods: This study employed a cross-sectional design with prospective data collection, in which 25 patients with PDM and 20 healthy controls (HCs) were recruited. The patients with PDM underwent fMRI scans both during the PDM during the pain phase (PDM-P) and nonpain phase (PDM-NP). The long-term effects of PDM on the brain was assessed by comparing PDM-NP findings with those of HCs, and the central mechanism of PDM was assessed by comparing the PDM-P findings with those of PDM-NP. To identify changes in brain function, the amplitude of low-frequency fluctuations and the regional homogeneity (ReHo) were measured. To assess changes in brain structure, voxel-based morphometry (VBM) was applied. The periaqueductal gray (PAG) was set as a region of for conducting seed-based whole-brain functional connectivity (FC) analysis. Subsequently, Pearson correlation analyses were employed to evaluate the associations between the abnormal brain region and the clinical information of the patients. Results: There were neither functional nor structural differences between patients in the PDM-NP and HCs. Compared with those in PDM-NP, those in PDM-P showed increased ReHo in the left dorsolateral prefrontal cortex (DLPFC) but decreased FC between PAG and right superior parietal gyrus, bilateral inferior parietal gyrus, right calcarine gyrus, left superior occipital gyrus, left precentral gyrus, right DLPFC, and left crus I of the cerebellar hemisphere. Conclusions: The results from this study suggest that the mechanism of central pain hypersensitivity of PDM may be related to the disorder of the FC between the PAG and descending pain modulation system, default mode network (DMN), and occipital lobe. These findings could help us better understand the pathophysiology of PDM from a neuroimaging perspective.

Effects of White Noise Sound on the Severity of Muscle Vaccination Pain in Children Under Two Years.

Objectives: Pain and its control is a significant health problem worldwide. The present study aimed to determine the effects of white noise (bird sound) on the severity of muscle vaccination pain in children under two years old. Materials & Methods: This study was a case-control study conducted in 2021. The samples included seventy children under two years old referred to the health centers in Ramsar City, Iran. The samples were selected using the convenient sampling method and divided into experimental and control groups. The data were collected using the demographic characteristics questionnaire, facial expression, and pain assessment in pediatric patients (FLACC). They were then analyzed by SPSS16 using an independent t-test and analysis of covariance (P<0.05). Results: A significant difference was observed between the severity of muscle vaccination pain in children in the two groups (p=0.042); the pain intensity mean in the experimental group (6.45±2.01) was lower than the control group (8.94±1.28). Conclusion: This method can be a harmless and inexpensive intervention to reduce pain intensity and behavioral pain responses in infants during painful procedures, especially vaccination.

Glutamatergic neurons in the paraventricular nucleus of the hypothalamus participate in the regulation of visceral pain induced by pancreatic cancer in mice.

Background: Visceral pain induced by pancreatic cancer seriously affects patients' quality of life, and there is no effective treatment, because the mechanism of its neural circuit is unknown. Therefore, the aim of this study is to explore the main neural circuit mechanism regulating visceral pain induced by pancreatic cancer in mice. Methods: The mouse model of pancreatic cancer visceral pain was established on C57BL/6N mice by pancreatic injection of mPAKPC-luc cells. Abdominal mechanical hyperalgesia and hunch score were performed to assess visceral pain; the pseudorabies virus (PRV) was used to identify the brain regions innervating the pancreas; the c-fos co-labeling method was used to ascertain the types of activated neurons; in vitro electrophysiological patch-clamp technique was used to record the electrophysiological activity of specific neurons; the calcium imaging technique was used to determine the calcium activity of specific neurons; specific neuron destruction and chemogenetics methods were used to explore whether specific neurons were involved in visceral pain induced by pancreatic cancer. Results: The PRV injected into the pancreas was detected in the paraventricular nucleus of the hypothalamus (PVN). Immunofluorescence staining showed that the majority of c-fos were co-labeled with glutamatergic neurons in the PVN. In vitro electrophysiological results showed that the firing frequency of glutamatergic neurons in the PVN was increased. The calcium imaging results showed that the calcium activity of glutamatergic neurons in the PVN was enhanced. Both specific destruction of glutamatergic neurons and chemogenetics inhibition of glutamatergic neurons in the PVN alleviated visceral pain induced by pancreatic cancer. Conclusions: Glutamatergic neurons in the PVN participate in the regulation of visceral pain induced by pancreatic cancer in mice, providing new insights for the discovery of effective targets for the treatment of pancreatic cancer visceral pain.

Perioperative intravenous lidocaine in thoracoscopic surgery for improved postoperative pain control: a randomized, placebo-controlled, double-blind, superiority trial.

Background: Pain, including associated pain management, remains a burden on patients after thoracic surgery. Our objective was to investigate whether perioperative intravenous administration of lidocaine reduces postoperative morphine consumption and pain intensity after video-assisted thoracoscopic surgery (VATS). Methods: In this double-blind, placebo-controlled superiority trial, patients undergoing VATS with a planned duration of ≤90 minutes were randomized within an intention-to-treat setting. Patients received either intravenous lidocaine or placebo as a bolus of 1.5 mg/kg 30 minutes before incision, followed by a continuous infusion of 3.0 mg/kg/hour until 2 hours after skin closure. Pain and morphine consumption were evaluated when resting and when coughing 1, 2, 4, 8, 16, 24, and 48 hours after skin closure and in a follow-up 14, 90, and 180 days postoperatively. Results: Twenty-eight patients were included in the lidocaine group, 24 in the placebo group. Patients' characteristics and preoperative pain scores were similar in both groups. When coughing, patients of the lidocaine group had less pain within 24 hours after skin closure than the placebo group (4.60±1.64 vs. 5.52±1.65; P=0.02). Morphine consumption was not statistically significantly lower in lidocaine group (18.22±12.87 vs. 21.26±9.39 mg; P=0.26). There were no significant differences between groups in secondary outcomes. Conclusions: Our results suggest that perioperative intravenous lidocaine administration reduces pain scores after VATS. The beneficial clinical effects are limited. Nevertheless, intravenous lidocaine may be helpful as part of a multimodal analgesia protocol or with patients in whom the use of other analgesics is contraindicated. Trial Registration: ClinicalTrials.gov NCT03677817.

Item-Specific Knee Injury and Osteoarthritis Outcome Score Characterization of Patients With Medial Meniscus Root Tear.

Background: Most studies regarding medial meniscus posterior root tear (MMPRT) report total Knee injury and Osteoarthritis Outcome Score (KOOS) subscale values as important patient-reported outcomes, but there are few symptom-specific characterizations of patients with MMPRT. Purpose/Hypothesis: The purpose of this study was to characterize the prevalence and severity of symptoms and functional limitations among patients with MMPRT based on item-level KOOS responses. It was hypothesized that patients with MMPRT would show similar symptoms to those of other meniscal tear types, with items from the KOOS pain subscale forming a majority of the most severe and prevalent symptoms. Study Design: Cross-sectional study; Level of evidence, 3. Methods: The records of 1466 patients with medial meniscus root tear between January 2017 and December 2021 at a single institution were reviewed. KOOS subscale scores and item-specific responses from initial evaluation were collected for each patient. Each KOOS item was scored on a scale from 1 (none/least severe) to 5 (extreme/most severe). Median and mean item-level responses were calculated and ranked in order of most to least severe. For statistical analysis, item-level prevalence rates were calculated as the proportion of patients reporting at least mild symptoms and ranked from most to least prevalent. Results: Included were 61 patients with MMPRT verified on magnetic resonance imaging (MRI). The most severe items according to item-level KOOS response were as follows: awareness of knee problem (mean, 4.62 [95% CI, 4.47-4.78]), difficulty jumping (mean, 4.06 [95% CI, 3.73-4.39]), difficulty twisting or pivoting (mean, 4.04 [95% CI, 3.76-4.32]), difficulty kneeling (mean, 3.98 [95% CI, 3.65-4.31]), and modification of lifestyle (mean, 3.94 [95% CI, 3.69-4.20]). The most prevalent items were knee stiffness later in the day, pain going up- or downstairs, difficulty ascending stairs, difficulty getting in and out of the car, difficulty twisting or pivoting, awareness of knee problem, and modification of lifestyle, with all patients reporting at least mild symptoms for each. Of the 11 most severe and prevalent symptoms, 8 came from the KOOS-Pain item-specific responses. Conclusion: Pain-related items made up a majority of the most severe and most prevalent symptoms as identified by the item-specific KOOS responses. However, meniscal symptoms commonly seen in other tear types, such as clicking and knee stiffness, were still quite prevalent in patients with MMPRT.

An Overview of the Effects of Tenapanor on Visceral Hypersensitivity in the Treatment of Irritable Bowel Syndrome with Constipation.

Background: Patients with irritable bowel syndrome with constipation (IBS-C) experience persistent abdominal pain, a common symptom leading to greater healthcare utilization and reports of treatment non-response. Clinically significant improvements in abdominal pain were observed in clinical trials of tenapanor, a first-in-class inhibitor of sodium/hydrogen exchanger isoform 3 (NHE3), for the treatment of IBS-C in adults. Aim: This narrative review reports the current knowledge about visceral hypersensitivity as a mechanism for abdominal pain in patients with IBS-C and explores the published evidence for hypothesized mechanisms by which tenapanor may reduce visceral hypersensitivity leading to the observed clinical response of decreased abdominal pain. Findings: Abdominal pain is experienced through activation and signaling of nociceptive dorsal root ganglia that innervate the gut. These sensory afferent neurons may become hypersensitized through signaling of transient receptor potential cation channel subfamily V member 1 (TRPV1), resulting in reduced action potential thresholds. TRPV1 signaling is also a key component of the proinflammatory cascade involving mast cell responses to macromolecule exposure following permeation through the intestinal epithelium. Indirect evidence of this pathway is supported by observations of higher pain in association with increased intestinal permeability in patients with IBS. Tenapanor reduces intestinal sodium absorption, leading to increased water retention in the intestinal lumen, thereby improving gastrointestinal motility. In animal models of visceral hypersensitivity, tenapanor normalized visceromotor responses and normalized TRPV1-mediated nociceptive signaling. Conclusion: By improving gastrointestinal motility, decreasing intestinal permeability and inflammation, and normalizing nociception through decreased TRPV1 signaling, tenapanor may reduce visceral hypersensitivity, leading to less abdominal pain in patients with IBS-C. Therapies that have demonstrated effects on visceral hypersensitivity may be the future direction for meaningful abdominal pain relief for patients with IBS-C.

Can botulinum toxin injection alleviate the pain of bruxism? A Bayesian network analysis and a single-arm analysis.

Background/purpose: There is inconsistent evidence regarding whether the botulinum toxin A (BTA) injection can relieve pain caused by bruxism. This study aimed to estimate the efficiency of BTA injection in relieving pain caused by bruxism at different follow-up periods. Materials and methods: Five electronic databases were searched from 2005 to 2022 using search terms related to botulinum toxin and bruxism. Only controlled clinical trials were included. Two investigators reviewed each article and discussed any disagreements until a consensus was reached. Pain outcomes as evaluated by the visual analogue scale (VAS) were subjected to single-arm and Bayesian network meta-analyses. Pooling data were measured by a random-effects model. Results: Eleven studies with a total of 365 bruxism patients were included. According to the single-arm analyses of the pooled data, the reduction in bruxism-related pain after BTA injection measured 4.06 points (95% CI = 3.37 to 4.75) on the VAS, and the pain relief was significant in the first 6 months after treatment (P < 0.01). According to the Bayesian analysis, BTA also resulted in significantly greater pain relief than oral splinting (mean difference (MD), -1.5; 95% credible interval (CrI) = -2.7 to -0.19) or saline injection (MD, -3.3; 95% CrI = -6.2 to -0.32). Conclusion: BTA significantly relieves the pain of bruxism for 6 months after injection, and its therapeutic efficacy was higher than that of oral splinting. Nevertheless, further long-term follow-up randomized controlled trials comparing BTA with other management or drugs are warranted.

Nerve Preparation and Recordings for Pharmacological Tests of Sensory and Nociceptive Fiber Conduction Ex Vivo.

Measuring signal propagation through nerves is a classical electrophysiological technique established decades ago to evaluate sensory and motor functions in the nervous system. The whole-nerve preparation provides a valuable model to investigate nerve function ex vivo; however, it requires specific knowledge to ensure successful and stable measurements. Although the methodology for sciatic nerve recordings has long existed, a method for reliable and long-lasting recordings from myelinated and non-myelinated (nociceptive) fibers still needs to be adapted for pharmacological testing. This protocol takes benefits from epineurium sheath removal for pharmacological tests and provides a detailed description of how to make accurate nerve preparations, from the dissection and handling of nerves to epineurium cleaning, fabrication of adaptable suction electrodes for appropriate fiber stimulation and recordings, setting of electrophysiological protocols for compound action potential (CAP) recordings to distinguish between myelinated and non-myelinated (nociceptive) fibers, and finally to the analysis of the datasets of CAP components. We also demonstrate the feasibility of CAP recordings from individual branches in epineurium-free nerve preparations and provide clues to help retain nerve viability and maintain stable recordings over time. Although a sciatic nerve preparation was used here, the methodology can be applied to other nerve-type preparations. Key features • Detailed and simplified protocol for peripheral nerve preparation for recording sensory inputs ex vivo. • Recordings from myelinated and non-myelinated (nociceptive) fibers can be performed hours after nerve preparation. • The protocol involves the epineurium removal to facilitate drug permeability into nerve tissue for pharmacological tests. • The protocol allows physiological and pathological studies (pain/chronic pain conditions).

Tryptophan metabolism and small fibre neuropathy: a correlation study.

Small nerve fibres located in the epidermis sense pain. Dysfunction of these fibres decreases the pain threshold known as small fibre neuropathy. Diabetes mellitus is accompanied by metabolic changes other than glucose, synergistically eliciting small fibre neuropathy. These findings suggest that various metabolic changes may be involved in small fibre neuropathy. Herein, we explored the correlation between pain sensation and changes in plasma metabolites in healthy Japanese subjects. The pain threshold evaluated from the intraepidermal electrical stimulation was used to quantify pain sensation in a total of 1021 individuals in the 2017 Iwaki Health Promotion Project. Participants with a pain threshold evaluated from the intraepidermal electrical stimulation index <0.20 mA were categorized into the pain threshold evaluated from the intraepidermal electrical stimulation index-low group (n = 751); otherwise, they were categorized into the pain threshold evaluated from the intraepidermal electrical stimulation index-high group (n = 270). Metabolome analysis of plasma was conducted using capillary electrophoresis time-of-flight mass spectrometry. The metabolite set enrichment analysis revealed that the metabolism of tryptophan was significantly correlated with the pain threshold evaluated from the intraepidermal electrical stimulation index in all participants (P < 0.05). The normalized level of tryptophan was significantly decreased in participants with a high pain threshold evaluated from the intraepidermal electrical stimulation index. In addition to univariate linear regression analyses, the correlation between tryptophan concentration and the pain threshold evaluated from the intraepidermal electrical stimulation index remained significant after adjustment for multiple factors (ß = -0.07615, P < 0.05). These findings indicate that specific metabolic changes are involved in the deterioration of pain thresholds. Here, we show that abnormal tryptophan metabolism is significantly correlated with an elevated pain threshold evaluated from the intraepidermal electrical stimulation index in the Japanese population. This correlation provides insight into the pathology and clinical application of small fibre neuropathy.