Graded brain fMRI response to somatic and visual acupuncture stimulation.

Increased stimulation can enhance acupuncture clinical response; however, the impact of acupuncture stimulation as "dosage" has rarely been studied. Furthermore, acupuncture can include both somatic and visual components. We assessed both somatic and visual acupuncture dosage effects on sensory ratings and brain response. Twenty-four healthy participants received somatic (needle inserted, manually stimulated) and visual (needle video, no manual stimulation) acupuncture over the leg at three different dosage levels (control, low-dose, and high-dose) during functional magnetic resonance imaging (fMRI). Participants reported the perceived deqi sensation for each acupuncture dose level. Blood-oxygen-level dependent imaging data were analyzed by general linear model and multivariate pattern analysis. For both somatic and visual acupuncture, reported deqi sensation increased with increased dosage of acupuncture stimulation. Brain fMRI analysis demonstrated that higher dosage of somatic acupuncture produced greater brain responses in sensorimotor processing areas, including anterior and posterior insula and secondary somatosensory cortex. For visual acupuncture, higher dosage of stimulation produced greater brain responses in visual-processing areas, including the middle temporal visual areas (V5/MT+) and occipital cortex. Psychophysical and psychophysiological responses to both somatic and visual acupuncture were graded in response to higher doses. Our findings suggest that acupuncture response may be enhanced by the dosage of needling-specific and nonspecific components, represented by different neural mechanisms.

Chronic Gut Inflammation and Dysbiosis in IBS: Unraveling Their Contribution to Atopic Dermatitis Progression.

Emerging evidence suggests a link between atopic dermatitis (AD) and gastrointestinal disorders, particularly in relation to gut microbial dysbiosis. This study explored the potential exacerbation of AD by gut inflammation and microbial imbalances using an irritable bowel syndrome (IBS) mouse model. Chronic gut inflammation was induced in the model by intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by a 4-week development period. We noted significant upregulation of proinflammatory cytokines in the colon and evident gut microbial dysbiosis in the IBS mice. Additionally, these mice exhibited impaired gut barrier function, increased permeability, and elevated systemic inflammation markers such as IL-6 and LPS. A subsequent MC903 challenge on the right cheek lasting for 7 days revealed more severe AD symptoms in IBS mice compared to controls. Further, fecal microbial transplantation (FMT) from IBS mice resulted in aggravated AD symptoms, a result similarly observed with FMT from an IBS patient. Notably, an increased abundance of Alistipes in the feces of IBS mice correlated with heightened systemic and localized inflammation in both the gut and skin. These findings collectively indicate that chronic gut inflammation and microbial dysbiosis in IBS are critical factors exacerbating AD, highlighting the integral relationship between gut and skin health.

The role of visual expectations in acupuncture analgesia: A quantitative electroencephalography study.

Acupuncture is a complex treatment comprising multisensory stimulation, including visual and tactile sensations and experiences of body ownership. The purpose of this study was to investigate the role of these three components of acupuncture stimulation in acupuncture analgesia. 40 healthy volunteers participated in the study and received acupuncture treatment under three different conditions (real-hand, rubber-hand synchronous, and rubber-hand asynchronous). The tolerance for heat pain stimuli was measured before and after treatment. Brain oscillation changes were also measured using electroencephalography (EEG). The pain tolerance was significantly increased after acupuncture treatment under all three conditions. Noticeable deqi (needle) sensations in response to acupuncture stimulation of the rubber hand were found under both rubber-hand synchronous and rubber-hand asynchronous conditions. Deqi sensations were significantly correlated with acupuncture analgesia only under the rubber-hand synchronous condition. Increased delta and decreased theta, alpha, beta, and gamma waves were observed after acupuncture treatment under all three conditions. Our findings clarified the role of cognitive components of acupuncture treatment in acupuncture analgesia through the rubber-hand illusion. This study is a first step toward separating various components of acupuncture analgesia, i.e. visual, tactile, and body ownership, and utilizing those components to maximize analgesic effects.

Plant Alkaloid Tetrandrine Is a Nuclear Receptor 4A1 Antagonist and Inhibits Panc-1 Cell Growth In Vitro and In Vivo.

The orphan nuclear receptor 4A1 (NR4A1) is highly expressed in human pancreatic cancer cells and exerts pro-oncogenic activity. In a previous study, we demonstrated that fangchinoline (FCN), a natural inhibitor of nuclear NR4A1, induces NR4A1-dependent apoptosis in human pancreatic cancer cells. In this study, we evaluated FCN and its structural analogs (berbamine, isotetrandrine, tetrandrine, and tubocurarine) for their inhibitory effects on NR4A1 transactivity, and confirmed that tetrandrine (TTD) showed the highest inhibitory effect in pancreatic cancer cells. Moreover, in a tryptophan fluorescence quenching assay, TTD directly bound to the ligand binding domain (LBD) of NR4A1 with a KD value of 10.60 µM. Treatment with TTD decreased proliferation and induced apoptosis in Panc-1 human pancreatic cancer cells in part through the reduced expression of the Sp1-dependent anti-apoptotic gene survivin and induction of ROS-mediated endoplasmic reticulum stress, which are the well-known NR4A1-dependent proapoptotic pathways. Furthermore, at a dose of 25 mg/kg/day, TTD reduced tumor growth in an athymic nude mouse xenograft model bearing Panc-1 cells. These data show that TTD is an NR4A1 antagonist and that modulation of the NR4A1-mediated pro-survival pathways is involved in the antitumor effects of TTD.

Distinguishing pain from nociception, salience, and arousal: How autonomic nervous system activity can improve neuroimaging tests of specificity.

Pain is a subjective, multidimensional experience that is distinct from nociception. A large body of work has focused on whether pain processing is supported by specific, dedicated brain circuits. Despite advances in human neuroscience and neuroimaging analysis, dissociating acute pain from other sensations has been challenging since both pain and non-pain stimuli evoke salience and arousal responses throughout the body and in overlapping brain circuits. In this review, we discuss these challenges and propose that brain-body interactions in pain can be leveraged in order to improve tests for pain specificity. We review brain and bodily responses to pain and nociception and extant efforts toward identifying pain-specific brain networks. We propose that autonomic nervous system activity should be used as a surrogate measure of salience and arousal to improve these efforts and enable researchers to parse out pain-specific responses in the brain, and demonstrate the feasibility of this approach using example fMRI data from a thermal pain paradigm. This new approach will improve the accuracy and specificity of functional neuroimaging analyses and help to overcome current difficulties in assessing pain specific responses in the human brain.

Spatial Information of Somatosensory Stimuli in the Brain: Multivariate Pattern Analysis of Functional Magnetic Resonance Imaging Data.

Background: Multivoxel pattern analysis has provided new evidence on somatotopic representation in the human brain. However, the effects of stimulus modality (e.g., penetrating needle versus non-penetrating touch) and level of classification (e.g., multiclass versus binary classification) on patterns of brain activity encoding spatial information of body parts have not yet been studied. We hypothesized that performance of brain-based prediction models may vary across the types of stimuli, and neural patterns of voxels in the SI and parietal cortex would significantly contribute to the prediction of stimulated locations. Objective: We aimed to (1) test whether brain responses to tactile stimuli could distinguish among stimulated locations on the body surface, (2) investigate whether the stimulus modality and number of classes affect classification performance, and (3) localize brain regions encoding the spatial information of somatosensory stimuli. Methods: Fifteen healthy participants completed two functional magnetic resonance imaging (MRI) scans and were stimulated via the insertion of acupuncture needles or by non-invasive touch stimuli (5.46-sized von Frey filament). Participants received the stimuli at four different locations on the upper and lower limbs (two sites each) for 5 min while blood-oxygen-level-dependent activity (BOLD) was measured using 3-Tesla MRI. We performed multivariate pattern analysis (MVPA) using parameter estimate images of each trial for each participant and the support vector classifier (SVC) function, and the prediction accuracy and other MVPA outcomes were evaluated using stratified five-fold cross validation. We estimated the significance of the classification accuracy using a permutation test with randomly labeled training data (n = 10,000). Searchlight analysis was conducted to identify brain regions associated with significantly higher accuracy compared to predictions based on chance as obtained from a random classifier. Results: For the four-class classification (classifying four stimulated points on the body), SVC analysis of whole-brain beta values in response to acupuncture stimulation was able to discriminate among stimulated locations (mean accuracy, 0.31; q < 0.01). The searchlight analysis found that values related to the right primary somatosensory cortex (SI) and intraparietal sulcus were significantly more accurate than those due to chance (p < 0.01). On the other hand, the same classifier did not predict stimulated locations accurately for touch stimulation (mean accuracy, 0.25; q = 0.66). For binary classification (discriminating between two stimulated body parts, i.e., the arm or leg), the SVC algorithm successfully predicted the stimulated body parts for both acupuncture (mean accuracy, 0.63; q < 0.001) and touch stimulation (mean accuracy, 0.60; q < 0.01). Searchlight analysis revealed that predictions based on the right SI, primary motor cortex (MI), paracentral gyrus, and superior frontal gyrus were significantly more accurate compared to predictions based on chance (p < 0.05). Conclusion: Our findings suggest that the SI, as well as the MI, intraparietal sulcus, paracentral gyrus, and superior frontal gyrus, is responsible for the somatotopic representation of body parts stimulated by tactile stimuli. The MVPA approach for identifying neural patterns encoding spatial information of somatosensory stimuli may be affected by the stimulus type (penetrating needle versus non-invasive touch) and the number of classes (classification of four small points on the body versus two large body parts). Future studies with larger samples will identify stimulus-specific neural patterns representing stimulated locations, independent of subjective tactile perception and emotional responses. Identification of distinct neural patterns of body surfaces will help in improving neural biomarkers for pain and other sensory percepts in the future.

Neural Network Underlying Recovery from Disowned Bodily States Induced by the Rubber Hand Illusion.

We used functional magnetic resonance imaging to investigate how causal influences between brain regions during the rubber hand illusion (RHI) are modulated by tactile and visual stimuli. We applied needle rotations during the RHI in two different ways: one was with the real hand (reinstantiation by tactile stimuli, R-TS) and the other was with the rubber hand (reinstantiation by visual stimuli, R-VS). We used dynamic causal modeling to investigate interactions among four relevant brain regions: the ventral premotor cortex (PMv), the intraparietal sulcus (IPS), the secondary somatosensory cortex (SII), and the lateral occipitotemporal cortex (LOC). The tactile aspects of needle rotations changed the effective connectivity by directly influencing activity in the SII, whereas visual aspects of needle rotation changed the effective connectivity by influencing both the SII and the LOC. The endogenous connectivity parameters between the IPS and the PMv were reduced significantly in the R-TS condition. The modulatory parameters between the IPS and the PMv were enhanced significantly in the R-TS condition. The connectivity patterns driven by disowned bodily states could be differentially modulated by tactile and visual afferent inputs. Effective connectivity between the parietal and frontal multimodal areas may play important roles in the reinstantiation of body ownership.

Psychological distress and attentional bias toward acne lesions in patients with acne.

Acne vulgaris is a common inflammatory disease that manifests on the face and affects appearance. In general, facial acne has a wide-ranging negative impact on the psychosocial functioning of acne sufferers and leaves physical and emotional scars. In the present study, we investigated whether patients with acne vulgaris demonstrate enhanced psychological bias when assessing the attractiveness of faces with acne symptoms and whether they devote greater selective attention to acne lesions than to acne-free (control) individuals. Participants viewed images of faces under two different skin (acne vs. acne-free) and emotional facial expression (happy and neutral) conditions. They rated the attractiveness of the faces, and the time spent fixating on the acne lesions was recorded with an eye tracker. We found that the gap in perceived attractiveness between acne and acne-free faces was greater for acne sufferers. Furthermore, patients with acne fixated longer on facial regions exhibiting acne lesions than did control participants irrespective of the facial expression depicted. In summary, patients with acne have a stronger attentional bias for acne lesions and focus more on the skin lesions than do those without acne. Clinicians treating the skin problems of patients with acne should consider these psychological and emotional scars.

Auditory influence on stickiness perception: an fMRI study of multisensory integration.

This study explored how the human brain perceives stickiness through tactile and auditory channels, especially when presented with congruent or incongruent intensity cues. In our behavioral and functional MRI (fMRI) experiments, we presented participants with adhesive tape stimuli at two different intensities. The congruent condition involved providing stickiness stimuli with matching intensity cues in both auditory and tactile channels, whereas the incongruent condition involved cues of different intensities. Behavioral results showed that participants were able to distinguish between the congruent and incongruent conditions with high accuracy. Through fMRI searchlight analysis, we tested which brain regions could distinguish between congruent and incongruent conditions, and as a result, we identified the superior temporal gyrus, known primarily for auditory processing. Interestingly, we did not observe any significant activation in regions associated with somatosensory or motor functions. This indicates that the brain dedicates more attention to auditory cues than to tactile cues, possibly due to the unfamiliarity of conveying the sensation of stickiness through sound. Our results could provide new perspectives on the complexities of multisensory integration, highlighting the subtle yet significant role of auditory processing in understanding tactile properties such as stickiness.

Neural Biomarkers for Identifying Atopic Dermatitis and Assessing Acupuncture Treatment Response Using Resting-State fMRI.

Purpose: Only a few studies have focused on the brain mechanisms underlying the itch processing in AD patients, and a neural biomarker has never been studied in AD patients. We aimed to develop a deep learning model-based neural signature which can extract the relevant temporal dynamics, discriminate between AD and healthy control (HC), and between AD patients who responded well to acupuncture treatment and those who did not. Patients and Methods: We recruited 41 AD patients (22 male, age mean ± SD: 24.34 ± 5.29) and 40 HCs (20 male, age mean ± SD: 26.4 ± 5.32), and measured resting-state functional MRI signals. After preprocessing, 38 functional regions of interest were applied to the functional MRI signals. A long short-term memory (LSTM) was used to extract the relevant temporal dynamics for classification and train the prediction model. Bootstrapping and 4-fold cross-validation were used to examine the significance of the models. Results: For the identification of AD patients and HC, we found that the supplementary motor area (SMA), posterior cingulate cortex (PCC), temporal pole, precuneus, and dorsolateral prefrontal cortex showed significantly greater prediction accuracy than the chance level. For the identification of high and low responder to acupuncture treatment, we found that the lingual-parahippocampal-fusiform gyrus, SMA, frontal gyrus, PCC and precuneus, paracentral lobule, and primary motor and somatosensory cortex showed significantly greater prediction accuracy than the chance level. Conclusion: We developed and evaluated a deep learning model-based neural biomarker that can distinguish between AD and HC as well as between AD patients who respond well and those who respond less to acupuncture. Using the intrinsic neurological abnormalities, it is possible to diagnose AD patients and provide personalized treatment regimens.

Revealing the mechanism and efficacy of natural products on treating the asthma: Current insights from traditional medicine to modern drug discovery.

Asthma remains a significant global health challenge, demanding innovative approaches to treatment. Traditional medicine has a rich history of using natural products to alleviate asthmatic symptoms. However, transitioning from these traditional remedies to modern drug discovery approaches has provided fresh insights into the mechanisms and effectiveness of these natural products. This study provides our comprehensive review, which examines the current state of knowledge in the treatment of asthma. It delves into the mechanisms through which natural products ameliorate asthma symptoms, and it discusses their potential in the development of novel therapeutic interventions. Our analysis reveals that natural products, traditionally employed for asthma relief, exhibit diverse mechanisms of action. These include anti-inflammatory, bronchodilatory, immunomodulatory effects, and reducing gene expression. In the context of modern drug discovery, these natural compounds serve as valuable candidates for the development of novel asthma therapies. The transition from traditional remedies to modern drug discovery represents a promising avenue for asthma treatment. Our review highlights the substantial efficacy of natural products in managing asthma symptoms, underpinned by well-defined mechanisms of action. By bridging the gap between traditional and contemporary approaches, we contribute to the growing body of knowledge in the field, emphasizing the potential of natural products in shaping the future of asthma therapy.

Acupuncture ameliorates atopic dermatitis by modulating gut barrier function in a gut microbiota-dependent manner in mice.

OBJECTIVE: Atopic dermatitis (AD) is a chronic inflammatory skin disease that may be linked to changes in the gut microbiome. Acupuncture has been proven to be effective in reducing AD symptoms without serious adverse events, but its underlying mechanism is not completely understood. The purpose of this study was to investigate whether the potential effect of acupuncture on AD is gut microbiota-dependent. METHODS: AD-like skin lesions were induced by applying MC903 topically to the cheek of the mouse. Acupuncture was done at the Gok-Ji (LI11) acupoints. AD-like symptoms were assessed by lesion scores, scratching behavior, and histopathological changes; intestinal barrier function was measured by fecal output, serum lipopolysaccharide levels, histopathological changes, and mRNA expression of markers involved in intestinal permeability and inflammation. Gut microbiota was profiled using 16S rRNA gene sequencing from fecal samples. RESULTS: Acupuncture effectively improved chronic itch as well as the AD-like skin lesions with epidermal thickening, and also significantly altered gut microbiota structure as revealed by ß-diversity indices and analysis of similarities. These beneficial effects were eliminated by antibiotic depletion of gut microbiota, but were reproduced in gut microbiota-depleted mice that received a fecal microbiota transplant from acupuncture-treated mice. Interestingly, AD mice had intestinal barrier dysfunction as indicated by increased intestinal permeability, atrophy of the mucosal structure (reduced villus height and crypt depth), decreased expression of tight junctions and mucus synthesis genes, and increased expression of inflammatory mediators in the ileum. Acupuncture attenuated these abnormalities, which was gut microbiota-dependent. CONCLUSION: Acupuncture ameliorates AD-like phenotypes in a gut microbiota-dependent manner and some of these positive benefits are explained by modulation of the intestinal barrier, providing new perspective for non-pharmacological strategies for modulating gut microbiota to prevent and treat AD. Please cite this article as: Yeom M, Ahn S, Hahm DH, Jang SY, Jang SH, Park SY, Jang JH, Park J, Oh JY, Lee IS, Kim K, Kwon SK, Park HJ. Acupuncture ameliorates atopic dermatitis by modulating gut barrier function in a gut microbiota-dependent manner in mice. J Integr Med. 2024; Epub ahead of print.

The multi-herbal decoction SH003 alleviates LPS-induced acute lung injury by targeting inflammasome and extracellular traps in neutrophils.

BACKGROUND: Acute lung injury (ALI) is a devastating condition caused by sepsis, pneumonia, trauma, and more recently, COVID-19. SH003, an herbal formula consisted of Astragalus membranaceus, Angelica gigas and Trichosanthes kirilowii, is known for its effects on cancer and immunoregulation. HYPOTHESIS/PURPOSE: Previous studies show SH003 exerts a promising anti-inflammatory effect. This study investigates the effect of modified SH003 on ALI using in silico, in vivo, and in vitro models. STUDY DESIGN AND METHODS: We performed in silico-based analysis of SH003 on ALI-related pathways. C57BL/6 mice were intraperitoneally subjected to lipopolysaccharide (LPS) to induce septic ALI, followed by oral administration of SH003 for 2 weeks. Dexamethasone was used as the positive control. Human peripheral blood-derived polymorphonuclear neutrophils (PMN) were used to investigate the effect and mechanisms of SH003 on neutrophil extracellular trap (NET) formation. RESULTS: Network pharmacology analysis suggested SH003 regulates lung inflammation by modulating NET formation. SH003 significantly reduced mortality in sepsis in vivo by inhibiting local and systemic inflammation, likely via nuclear factor kappa B and mitogen-activated protein kinase pathways-mediated inflammasome suppression. SH003 also decreased NET-related markers in lung tissues and inhibited LPS- and phorbol myristate acetate-induced NET formation in PMN. Cytometry time-of-flight analysis confirmed regulation of NETosis-related pathways by SH003. CONCLUSION: SH003 effectively inhibits excessive immune responses in the lung by suppressing inflammasome activation and NET formation. These findings suggest SH003 as a potential therapeutic agent for septic ALI.

Role of gut-derived bacterial lipopolysaccharide and peripheral TLR4 in immobilization stress-induced itch aggravation in a mouse model of atopic dermatitis.

Psychological stress and intestinal leakage are key factors in atopic dermatitis (AD) recurrence and exacerbation. Here, we demonstrate the mechanism underlying bacterial translocation across intestinal epithelial barrier damaged due to stress and further aggravation of trimellitic anhydride (TMA)-induced itch, which remain unclear, in AD mice. Immobilization (IMO) stress exacerbated scratching bouts and colon histological damage, and increased serum corticosterone and lipopolysaccharide (LPS). Orally administered fluorescein isothiocyanate (FITC)-dextran and surgically injected (into the colon) Cy5.5-conjugated LPS were detected in the serum and skin after IMO stress, respectively. The relative abundance of aerobic or facultative anaerobic bacteria was increased in the colon mucus layer, and Lactobacillus murinus, E. coli, Staphylococcus nepalensis, and several strains of Bacillus sp. were isolated from the spleens and mesenteric lymph nodes. Oral antibiotics or intestinal permeability blockers, such as lubiprostone (Lu), 2,4,6-triaminopyrimidine (TAP) and ML-7, inhibited IMO stress-associated itch; however, it was reinduced through intradermal or i.p. injection of LPS without IMO stress. I.p. injection of TAK-242 (resatorvid), a TLR4 inhibitor, abrogated IMO stress-associated itch, which was also confirmed in TLR4-KO mice. IMO stress alone did not cause itch in naïve mice. IMO stress-induced itch aggravation in TMA-treated AD mice might be attributed to the translocation of gut-derived bacterial cells and LPS, which activates peripheral TLR4 signaling.

Central Regulation of Eating Behaviors in Humans: Evidence from Functional Neuroimaging Studies.

Neuroimaging has great potential to provide insight into the neural response to food stimuli. Remarkable advances have been made in understanding the neural activity underlying food perception, not only in normal eating but also in obesity, eating disorders, and disorders of gut-brain interaction in recent decades. In addition to the abnormal brain function in patients with eating disorders compared to healthy controls, new therapies, such as neurofeedback and neurostimulation techniques, have been developed that target the malfunctioning brain regions in patients with eating disorders based on the results of neuroimaging studies. In this review, we present an overview of early and more recent research on the central processing and regulation of eating behavior in healthy and patient populations. In order to better understand the relationship between the gut and the brain as well as the neural mechanisms underlying abnormal ingestive behaviors, we also provide suggestions for future directions to enhance our current methods used in food-related neuroimaging studies.

Acupuncture treatment for functional gastrointestinal disorders: Identification of major acupoints using network analysis.

Background: Using network analysis, we sought to determine the acupoints most commonly used to treat functional gastrointestinal disorders (FGIDs), particularly functional dyspepsia (FD) and irritable bowel syndrome (IBS). Methods: To explore the acupoint patterns used for FGID, data on acupoint combinations for FD and IBS were gathered from systematic reviews. Network analysis was used to determine the degree, closeness centrality, betweenness centrality, and eigenvector centrality of each acupoint. The most common acupoint combinations for FD and IBS were examined based on the eigenvector centrality. Results: Network analysis revealed that CV12, ST25, ST36, CV10, and LR3, which had the highest eigenvector centrality values, were the main acupoints for treating FGID. CV12 was the main acupoint for treating FD, while ST25 was the hub acupoint for treating IBS in the abdomen. ST36, LR3, and PC6 were the key peripheral acupoints for FD and IBS. Conclusions: Using network analysis, we provided data that will aid the selection of both general and specific acupoints for FD and IBS, along with spatial information (i.e., the positions of acupoints on a body map). These findings could be applied in future acupuncture research on therapy for gastrointestinal system dysfunction. They may also help bridge the gap between the traditional meridian theory, which assumes that there is a link between diseases/symptoms and the specific body region being treated, and real-world clinical evidence.

A prospective observational study of optimal acupoint selection on patients with functional gastrointestinal disorders.

INTRODUCTION: Functional gastrointestinal disorders (FGIDs), which include irritable bowel syndrome (IBS) and functional dyspepsia (FD), are common gastrointestinal (GI) diseases that have a large financial impact on patients' quality of life (QoL). Traditional Korean medicine has a particular diagnostic pattern for treating FGIDs. However, FGIDs have not been thoroughly explored because of their complexity. In this proposed study, we will investigate the acupoint selection pattern for FGID patients with various disease patterns, and further determine the best acupoints for treating FGID patients using a machine-learning algorithm. METHODS: We will collect clinical data from 15 multi-center Korean medical clinics that treat FGID as part of an observational study registry. Patients who meet the criteria will be added to the registry after screening. They will receive a maximum 4-week treatment, and they will respond 3 times to a series of questions. We will investigate how doctors of FGID patients with diverse disease patterns choose the acupoints, and we will use a machine learning technique to identify the best acupoints for treating FGID patients. DISCUSSION: This will be the first multi-center observational registry study to assess how traditional Korean medical practitioners diagnose and treat patients in the real world. The findings will shed light on how traditional Korean medicine treats FGIDs and demonstrate the rationale for the diagnostic and acupuncture treatment flow.

Sensory and emotional responses to deep pressure stimulation at myofascial trigger points: a pilot study.

Objective: Although manual pressure, such as that used during a massage, is often associated with pain, it can simultaneously be perceived as pleasant when applied to certain body areas. We hypothesized that stimulation of myofascial trigger points (TPs) leads to simultaneous pain and pleasure. TPs are hyperirritable points located in the taut band of the skeletal muscle. Method: In this study, we measured the muscle tone, muscle stiffness, and pressure pain threshold of TPs and control points in the left brachioradialis muscle of 48 healthy participants. We also applied deep compression to the two points and collected subjective data on pain, pleasantness, unpleasantness, and relief. Result: Greater muscle stiffness was observed in the TPs versus control points (t = 6.55, p < 0.001), and the pain threshold was significantly lower in the TPs (t = -6.21, p < 0.001). Unpleasantness ratings after deep compression were significantly lower in the TPs compared with control points (t = -2.68, p < 0.05). Participants experienced greater relief at the TPs compared with control points (t = 2.01, p < 0.05), although the perceived pain did not differ between the two types of points. Conclusion: We compared the properties of TPs and control points, and found that deep compression at TPs was associated with higher muscle tone and stiffness, lower unpleasantness ratings, and higher relief ratings compared with the control points. These findings suggest that, at least for some TPs, pain and pleasantness are simultaneously elicited by deep pressure stimulation.

Enhanced Empathic Pain by Facial Feedback.

The facial feedback hypothesis states that feedback from cutaneous and muscular afferents affects our emotion. Based on the facial feedback hypothesis, the purpose of this study was to determine whether enhancing negative emotion by activating a facial muscle (corrugator supercilii) increases the intensity of cognitive and emotional components of empathic pain. We also assessed whether the muscle contraction changed the pupil size, which would indicate a higher level of arousal. Forty-eight individuals completed 40 muscular contraction and relaxation trials while looking at images of five male and five female patients with neutral and painful facial expressions, respectively. Participants were asked to rate (1) how much pain the patient was in, and (2) how unpleasant their own feelings were. We also examined their facial muscle activities and changes in pupil size. No significant differences in pain or unpleasantness ratings were detected for the neutral face between the two conditions; however, the pain and unpleasantness ratings for the painful face were considerably higher in the contraction than relaxation condition. The pupils were considerably larger in the contraction than relaxation condition for both the painful and neutral faces. Our findings indicate that, by strengthening the corrugator supercilii, facial feedback can affect both the cognitive evaluative and affective sharing aspects of empathic pain.