The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Qasim Aziz - One of the best experts on this subject based on the ideXlab platform.
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effect of slow deep breathing on Visceral Pain perception and its underlying psychophysiological mechanisms
Neurogastroenterology and Motility, 2021Co-Authors: Qasim Aziz, Ali Gholamrezaei, Ilse Van Diest, Ans Pauwels, Jan Tack, Johan W S Vlaeyen, Lukas Van OudenhoveAbstract:BACKGROUND Studies using somatic Pain models have shown the hypoalgesic effects of slow, deep breathing. We evaluated the effect of slow, deep breathing on Visceral Pain and explored putative mediating mechanisms including autonomic and emotional responses. METHODS Fifty-seven healthy volunteers (36 females, mean age = 22.0 years) performed controlled, deep breathing at a slow frequency (6 breaths per minute), controlled breathing at a normal frequency (14 breaths per minute; active control), and uncontrolled breathing (no-treatment control) in randomized order. Moderate Painful stimuli were given during each condition by delivering electrical stimulation in the distal esophagus. Participants rated Pain intensity after each stimulation. Heart rate variability and self-reported arousal were measured during each condition. KEY RESULTS Compared to uncontrolled breathing, Pain intensity was lower during slow, deep breathing (Cohen's d = 0.40) and normal controlled breathing (d = 0.47), but not different between slow, deep breathing and normal controlled breathing. Arousal was lower (d = 0.53, 0.55) and heart rate variability was higher (d = 0.70, 0.86) during slow, deep breathing compared to the two control conditions. The effect of slow, deep breathing on Pain was not mediated by alterations in heart rate variability or arousal but was moderated by Pain catastrophizing. CONCLUSIONS AND INFERENCES Slow, deep breathing can reduce Visceral Pain intensity. However, the effect is not specific to the slow breathing frequency and is not mediated by autonomic or emotional responses, suggesting other underlying mechanisms (notably distraction). Whether a long-term practice of slow, deep breathing can influence (clinical) Visceral Pain warrants to be investigated.
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the iasp classification of chronic Pain for icd 11 chronic secondary Visceral Pain
Pain, 2019Co-Authors: Qasim Aziz, Maria Adele Giamberardino, Antonia Barke, Beatrice Korwisi, Andrew P Baranowski, Ursula Wesselmann, Winfried Rief, Rolfdetlef TreedeAbstract:Chronic Visceral Pain is a frequent and disabling condition. Despite high prevalence and impact, chronic Visceral Pain is not represented in ICD-10 in a systematic manner. Chronic secondary Visceral Pain is chronic Pain secondary to an underlying condition originating from internal organs of the head or neck region or of the thoracic, abdominal, or pelvic regions. It can be caused by persistent inflammation, by vascular mechanisms or by mechanical factors. The Pain intensity is not necessarily fully correlated with the disease process, and the chronic Visceral Pain may persist beyond successful treatment of the underlying cause. This article describes how a new classification of chronic secondary Visceral Pain is intended to facilitate the diagnostic process and to enable the collection of accurate epidemiological data. Furthermore, it is hoped that the new classification will improve the tailoring of patient-centered Pain treatment of chronic secondary Visceral Pain and stimulate research. Chronic secondary Visceral Pain should be distinguished from chronic primary Visceral Pain states that are considered diseases in their own right.
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preliminary report parasympathetic tone links to functional brain networks during the anticipation and experience of Visceral Pain
Scientific Reports, 2018Co-Authors: James K Ruffle, Qasim Aziz, Steven J Coen, Adam D Farmer, Vincent Giampietro, Steven WilliamsAbstract:The mechanisms that underpin the anti-nociceptive effect of the parasympathetic nervous system (PNS) on Visceral Pain remain incompletely understood. We sought to describe the effect of resting parasympathetic tone on functional brain networks during the anticipation and experience of oesophageal Pain. 21 healthy participants had their resting cardiac vagal tone (CVT), a validated measure of the PNS, quantified, and underwent functional magnetic resonance imaging during the anticipation and experience of Painful oesophageal distention. The relationship between resting CVT and functional brain networks was examined using 11 hypothesis-driven nodes and network-based statistics. A network comprising all nodes was apparent in individuals with high resting CVT, compared to those with low CVT, during oesophageal Pain (family wise error rate (FWER)-corrected p < 0.048). Functional connections included the thalamus-amygdala, thalamus-hypothalamus, hypothalamus-nucleus accumbens, amygdala-pallidum, pallidum-nucleus accumbens and insula-pallidum. A smaller network was seen during Pain anticipation, comprising the amygdala, pallidum and anterior insula (FWER-corrected p < 0.049). These findings suggest that PNS tone is associated with functional brain networks during the anticipation and experience of Visceral Pain. Given the role of these subcortical regions in the descending inhibitory modulation of Pain, these networks may represent a potential neurobiological explanation for the anti-nociceptive effect of the PNS.
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Preliminary report: parasympathetic tone links to functional brain networks during the anticipation and experience of Visceral Pain
Nature Publishing Group, 2018Co-Authors: James K Ruffle, Qasim Aziz, Steven J Coen, Vincent Giampietro, Steven C. R. Williams, Adam D FarmerAbstract:Abstract The mechanisms that underpin the anti-nociceptive effect of the parasympathetic nervous system (PNS) on Visceral Pain remain incompletely understood. We sought to describe the effect of resting parasympathetic tone on functional brain networks during the anticipation and experience of oesophageal Pain. 21 healthy participants had their resting cardiac vagal tone (CVT), a validated measure of the PNS, quantified, and underwent functional magnetic resonance imaging during the anticipation and experience of Painful oesophageal distention. The relationship between resting CVT and functional brain networks was examined using 11 hypothesis-driven nodes and network-based statistics. A network comprising all nodes was apparent in individuals with high resting CVT, compared to those with low CVT, during oesophageal Pain (family wise error rate (FWER)-corrected p
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sex differences in brain response to anticipated and experienced Visceral Pain in healthy subjects
American Journal of Physiology-gastrointestinal and Liver Physiology, 2013Co-Authors: Michiko Kano, Qasim Aziz, Shin Fukudo, Steven J Coen, Adam D Farmer, Vincent Giampietro, Michael Brammer, Steven WilliamsAbstract:Women demonstrate higher Pain sensitivity and prevalence of chronic Visceral Pain conditions such as functional gastrointestinal disorders than men. The role of sex differences in the brain processing of Visceral Pain is still unclear. In 16 male and 16 female healthy subjects we compared personality, anxiety levels, skin conductance response (SCR), and brain processing using functional MRI during anticipation and Pain induced by esophageal distension at Pain toleration level. There was no significant difference in personality scores, anxiety levels, SCR, and subjective ratings of Pain between sexes. In group analysis, both men and women demonstrated a similar pattern of brain activation and deactivation during anticipation and Pain consistent with previous reports. However, during anticipation women showed significantly greater activation in the cuneus, precuneus, and supplementary motor area (SMA) and stronger deactivation in the right amygdala and left parahippocampal gyrus, whereas men demonstrated greater activation in the cerebellum. During Pain, women demonstrated greater activation in the midcingulate cortex, anterior insula, premotor cortex, and cerebellum and stronger deactivation in the caudate, whereas men showed increased activity in the SMA. The pattern of brain activity suggests that, during anticipation, women may demonstrate stronger limbic inhibition, which is considered to be a cognitive modulation strategy for impending Painful stimulation. During Pain, women significantly activate brain areas associated with the affective and motivation components of Pain. These responses may underlie the sex differences that exist in Pain conditions, whereby women may attribute more emotional importance to Painful stimuli compared with men.
Adam D Farmer - One of the best experts on this subject based on the ideXlab platform.
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preliminary report parasympathetic tone links to functional brain networks during the anticipation and experience of Visceral Pain
Scientific Reports, 2018Co-Authors: James K Ruffle, Qasim Aziz, Steven J Coen, Adam D Farmer, Vincent Giampietro, Steven WilliamsAbstract:The mechanisms that underpin the anti-nociceptive effect of the parasympathetic nervous system (PNS) on Visceral Pain remain incompletely understood. We sought to describe the effect of resting parasympathetic tone on functional brain networks during the anticipation and experience of oesophageal Pain. 21 healthy participants had their resting cardiac vagal tone (CVT), a validated measure of the PNS, quantified, and underwent functional magnetic resonance imaging during the anticipation and experience of Painful oesophageal distention. The relationship between resting CVT and functional brain networks was examined using 11 hypothesis-driven nodes and network-based statistics. A network comprising all nodes was apparent in individuals with high resting CVT, compared to those with low CVT, during oesophageal Pain (family wise error rate (FWER)-corrected p < 0.048). Functional connections included the thalamus-amygdala, thalamus-hypothalamus, hypothalamus-nucleus accumbens, amygdala-pallidum, pallidum-nucleus accumbens and insula-pallidum. A smaller network was seen during Pain anticipation, comprising the amygdala, pallidum and anterior insula (FWER-corrected p < 0.049). These findings suggest that PNS tone is associated with functional brain networks during the anticipation and experience of Visceral Pain. Given the role of these subcortical regions in the descending inhibitory modulation of Pain, these networks may represent a potential neurobiological explanation for the anti-nociceptive effect of the PNS.
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Preliminary report: parasympathetic tone links to functional brain networks during the anticipation and experience of Visceral Pain
Nature Publishing Group, 2018Co-Authors: James K Ruffle, Qasim Aziz, Steven J Coen, Vincent Giampietro, Steven C. R. Williams, Adam D FarmerAbstract:Abstract The mechanisms that underpin the anti-nociceptive effect of the parasympathetic nervous system (PNS) on Visceral Pain remain incompletely understood. We sought to describe the effect of resting parasympathetic tone on functional brain networks during the anticipation and experience of oesophageal Pain. 21 healthy participants had their resting cardiac vagal tone (CVT), a validated measure of the PNS, quantified, and underwent functional magnetic resonance imaging during the anticipation and experience of Painful oesophageal distention. The relationship between resting CVT and functional brain networks was examined using 11 hypothesis-driven nodes and network-based statistics. A network comprising all nodes was apparent in individuals with high resting CVT, compared to those with low CVT, during oesophageal Pain (family wise error rate (FWER)-corrected p
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sex differences in brain response to anticipated and experienced Visceral Pain in healthy subjects
American Journal of Physiology-gastrointestinal and Liver Physiology, 2013Co-Authors: Michiko Kano, Qasim Aziz, Shin Fukudo, Steven J Coen, Adam D Farmer, Vincent Giampietro, Michael Brammer, Steven WilliamsAbstract:Women demonstrate higher Pain sensitivity and prevalence of chronic Visceral Pain conditions such as functional gastrointestinal disorders than men. The role of sex differences in the brain processing of Visceral Pain is still unclear. In 16 male and 16 female healthy subjects we compared personality, anxiety levels, skin conductance response (SCR), and brain processing using functional MRI during anticipation and Pain induced by esophageal distension at Pain toleration level. There was no significant difference in personality scores, anxiety levels, SCR, and subjective ratings of Pain between sexes. In group analysis, both men and women demonstrated a similar pattern of brain activation and deactivation during anticipation and Pain consistent with previous reports. However, during anticipation women showed significantly greater activation in the cuneus, precuneus, and supplementary motor area (SMA) and stronger deactivation in the right amygdala and left parahippocampal gyrus, whereas men demonstrated greater activation in the cerebellum. During Pain, women demonstrated greater activation in the midcingulate cortex, anterior insula, premotor cortex, and cerebellum and stronger deactivation in the caudate, whereas men showed increased activity in the SMA. The pattern of brain activity suggests that, during anticipation, women may demonstrate stronger limbic inhibition, which is considered to be a cognitive modulation strategy for impending Painful stimulation. During Pain, women significantly activate brain areas associated with the affective and motivation components of Pain. These responses may underlie the sex differences that exist in Pain conditions, whereby women may attribute more emotional importance to Painful stimuli compared with men.
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neuroticism influences brain activity during the experience of Visceral Pain
Gastroenterology, 2011Co-Authors: Steven J Coen, Michiko Kano, Adam D Farmer, Veena Kumari, Vincent Giampietro, Michael Brammer, Steven Williams, Qasim AzizAbstract:Background & Aims One particularly important individual dynamic known to influence the experience of Pain is neuroticism, of which little is known about in Visceral Pain research. Our aim was to study the relationship between neuroticism, psychophysiologic response, and brain processing of Visceral Pain. Methods Thirty-one healthy volunteers (15 male; age range, 22–38 years) participated in the study. The Eysenck Personality Questionnaire was used to assess neuroticism. Skin conductance level, Pain ratings, and functional magnetic resonance imaging data were acquired during anticipation of Pain and Painful esophageal distention. The effect of neuroticism was assessed using correlation analysis. Results There was a wide spread of neuroticism scores (range, 0–22) but no influence of neuroticism on skin conductance level and Pain tolerance or Pain ratings. However, a positive correlation between brain activity and neuroticism during anticipation was found in regions associated with emotional and cognitive Pain processing, including the parahippocampus, insula, thalamus, and anterior cingulate cortex. These regions showed a negative correlation with neuroticism during Pain ( P Conclusions This study provides novel data suggesting higher neuroticism is associated with engagement of brain regions responsible for emotional and cognitive appraisal during anticipation of Pain but reduced activity in these regions during Pain. This may reflect a maladaptive mechanism in those with higher neuroticism that promotes overarousal during anticipation and avoidance coping during Pain.
Steven J Coen - One of the best experts on this subject based on the ideXlab platform.
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preliminary report parasympathetic tone links to functional brain networks during the anticipation and experience of Visceral Pain
Scientific Reports, 2018Co-Authors: James K Ruffle, Qasim Aziz, Steven J Coen, Adam D Farmer, Vincent Giampietro, Steven WilliamsAbstract:The mechanisms that underpin the anti-nociceptive effect of the parasympathetic nervous system (PNS) on Visceral Pain remain incompletely understood. We sought to describe the effect of resting parasympathetic tone on functional brain networks during the anticipation and experience of oesophageal Pain. 21 healthy participants had their resting cardiac vagal tone (CVT), a validated measure of the PNS, quantified, and underwent functional magnetic resonance imaging during the anticipation and experience of Painful oesophageal distention. The relationship between resting CVT and functional brain networks was examined using 11 hypothesis-driven nodes and network-based statistics. A network comprising all nodes was apparent in individuals with high resting CVT, compared to those with low CVT, during oesophageal Pain (family wise error rate (FWER)-corrected p < 0.048). Functional connections included the thalamus-amygdala, thalamus-hypothalamus, hypothalamus-nucleus accumbens, amygdala-pallidum, pallidum-nucleus accumbens and insula-pallidum. A smaller network was seen during Pain anticipation, comprising the amygdala, pallidum and anterior insula (FWER-corrected p < 0.049). These findings suggest that PNS tone is associated with functional brain networks during the anticipation and experience of Visceral Pain. Given the role of these subcortical regions in the descending inhibitory modulation of Pain, these networks may represent a potential neurobiological explanation for the anti-nociceptive effect of the PNS.
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Preliminary report: parasympathetic tone links to functional brain networks during the anticipation and experience of Visceral Pain
Nature Publishing Group, 2018Co-Authors: James K Ruffle, Qasim Aziz, Steven J Coen, Vincent Giampietro, Steven C. R. Williams, Adam D FarmerAbstract:Abstract The mechanisms that underpin the anti-nociceptive effect of the parasympathetic nervous system (PNS) on Visceral Pain remain incompletely understood. We sought to describe the effect of resting parasympathetic tone on functional brain networks during the anticipation and experience of oesophageal Pain. 21 healthy participants had their resting cardiac vagal tone (CVT), a validated measure of the PNS, quantified, and underwent functional magnetic resonance imaging during the anticipation and experience of Painful oesophageal distention. The relationship between resting CVT and functional brain networks was examined using 11 hypothesis-driven nodes and network-based statistics. A network comprising all nodes was apparent in individuals with high resting CVT, compared to those with low CVT, during oesophageal Pain (family wise error rate (FWER)-corrected p
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sex differences in brain response to anticipated and experienced Visceral Pain in healthy subjects
American Journal of Physiology-gastrointestinal and Liver Physiology, 2013Co-Authors: Michiko Kano, Qasim Aziz, Shin Fukudo, Steven J Coen, Adam D Farmer, Vincent Giampietro, Michael Brammer, Steven WilliamsAbstract:Women demonstrate higher Pain sensitivity and prevalence of chronic Visceral Pain conditions such as functional gastrointestinal disorders than men. The role of sex differences in the brain processing of Visceral Pain is still unclear. In 16 male and 16 female healthy subjects we compared personality, anxiety levels, skin conductance response (SCR), and brain processing using functional MRI during anticipation and Pain induced by esophageal distension at Pain toleration level. There was no significant difference in personality scores, anxiety levels, SCR, and subjective ratings of Pain between sexes. In group analysis, both men and women demonstrated a similar pattern of brain activation and deactivation during anticipation and Pain consistent with previous reports. However, during anticipation women showed significantly greater activation in the cuneus, precuneus, and supplementary motor area (SMA) and stronger deactivation in the right amygdala and left parahippocampal gyrus, whereas men demonstrated greater activation in the cerebellum. During Pain, women demonstrated greater activation in the midcingulate cortex, anterior insula, premotor cortex, and cerebellum and stronger deactivation in the caudate, whereas men showed increased activity in the SMA. The pattern of brain activity suggests that, during anticipation, women may demonstrate stronger limbic inhibition, which is considered to be a cognitive modulation strategy for impending Painful stimulation. During Pain, women significantly activate brain areas associated with the affective and motivation components of Pain. These responses may underlie the sex differences that exist in Pain conditions, whereby women may attribute more emotional importance to Painful stimuli compared with men.
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neuroticism influences brain activity during the experience of Visceral Pain
Gastroenterology, 2011Co-Authors: Steven J Coen, Michiko Kano, Adam D Farmer, Veena Kumari, Vincent Giampietro, Michael Brammer, Steven Williams, Qasim AzizAbstract:Background & Aims One particularly important individual dynamic known to influence the experience of Pain is neuroticism, of which little is known about in Visceral Pain research. Our aim was to study the relationship between neuroticism, psychophysiologic response, and brain processing of Visceral Pain. Methods Thirty-one healthy volunteers (15 male; age range, 22–38 years) participated in the study. The Eysenck Personality Questionnaire was used to assess neuroticism. Skin conductance level, Pain ratings, and functional magnetic resonance imaging data were acquired during anticipation of Pain and Painful esophageal distention. The effect of neuroticism was assessed using correlation analysis. Results There was a wide spread of neuroticism scores (range, 0–22) but no influence of neuroticism on skin conductance level and Pain tolerance or Pain ratings. However, a positive correlation between brain activity and neuroticism during anticipation was found in regions associated with emotional and cognitive Pain processing, including the parahippocampus, insula, thalamus, and anterior cingulate cortex. These regions showed a negative correlation with neuroticism during Pain ( P Conclusions This study provides novel data suggesting higher neuroticism is associated with engagement of brain regions responsible for emotional and cognitive appraisal during anticipation of Pain but reduced activity in these regions during Pain. This may reflect a maladaptive mechanism in those with higher neuroticism that promotes overarousal during anticipation and avoidance coping during Pain.
Dali Lu - One of the best experts on this subject based on the ideXlab platform.
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zd 7288 an hcn channel blocker attenuates chronic Visceral Pain in irritable bowel syndrome like rats
World Journal of Gastroenterology, 2014Co-Authors: Yu Chen, Ying Tang, Aiqin Chen, Dali LuAbstract:AIM: To investigate the effects of ZD 7288, a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, on rats with chronic Visceral Pain. METHODS: Rats with Visceral hypersensitivity were generated using neonatal colon irritation during postnatal days 8-15 as described previously. Visceral hypersensitivity was evaluated using electromyographic (EMG) responses of abdominal external oblique muscles to 20-80 mmHg colorectal distentions (CRD). Abdominal withdrawal reflex (AWR) scores and Pain thresholds were also detected in adult rats. Different doses of ZD 7288 (25, 50, and 100 nmol/L) were intrathecally administered in rats to study the role of spinal HCN channel in chronic Visceral hypersensitivity. RESULTS: EMG responses to 20-80 mmHg CRD and AWR scores under 20-60 mmHg CRD significantly increased in rats with Visceral hypersensitivity compared to control rats (P < 0.05). The Pain threshold in rats with Visceral hypersensitivity significantly decreased compared to control rats (P < 0.05). Treatment with 50-100 nmol/L ZD 7288 significantly inhibited EMG responses (16%-62%, 80-20 mmHg CRD, P < 0.05) and AWR scores (24%-37%, 40-20 mmHg CRD, P < 0.05; 12%-61%, 80-20 mmHg CRD, P < 0.05, respectively), and significantly increased Pain thresholds (32%-77%, P < 0.05). CONCLUSION: Spinal HCN channels may play an important role in chronic Visceral hypersensitivity.
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zd 7288 an hcn channel blocker attenuates chronic Visceral Pain in irritable bowel syndrome like rats
World Journal of Gastroenterology, 2014Co-Authors: Yu Chen, Ying Tang, Aiqin Chen, Dali LuAbstract:AIM: To investigate the effects of ZD 7288, a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, on rats with chronic Visceral Pain. METHODS: Rats with Visceral hypersensitivity were generated using neonatal colon irritation during postnatal days 8-15 as described previously. Visceral hypersensitivity was evaluated using electromyographic (EMG) responses of abdominal external oblique muscles to 20-80 mmHg colorectal distentions (CRD). Abdominal withdrawal reflex (AWR) scores and Pain thresholds were also detected in adult rats. Different doses of ZD 7288 (25, 50, and 100 nmol/L) were intrathecally administered in rats to study the role of spinal HCN channel in chronic Visceral hypersensitivity. RESULTS: EMG responses to 20-80 mmHg CRD and AWR scores under 20-60 mmHg CRD significantly increased in rats with Visceral hypersensitivity compared to control rats (P < 0.05). The Pain threshold in rats with Visceral hypersensitivity significantly decreased compared to control rats (P < 0.05). Treatment with 50-100 nmol/L ZD 7288 significantly inhibited EMG responses (16%-62%, 80-20 mmHg CRD, P < 0.05) and AWR scores (24%-37%, 40-20 mmHg CRD, P < 0.05; 12%-61%, 80-20 mmHg CRD, P < 0.05, respectively), and significantly increased Pain thresholds (32%-77%, P < 0.05). CONCLUSION: Spinal HCN channels may play an important role in chronic Visceral hypersensitivity.
John F Cryan - One of the best experts on this subject based on the ideXlab platform.
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microbiota regulates Visceral Pain in the mouse
eLife, 2017Co-Authors: Pauline Luczynski, Timothy G Dinan, Monica Tramullas, Maria F Viola, Fergus Shanahan, Gerard Clarke, Siobhain M Omahony, John F CryanAbstract:The perception of Visceral Pain is a complex process involving the spinal cord and higher order brain structures. Increasing evidence implicates the gut microbiota as a key regulator of brain and behavior, yet it remains to be determined if gut bacteria play a role in Visceral sensitivity. We used germ-free mice (GF) to assess Visceral sensitivity, spinal cord gene expression and Pain-related brain structures. GF mice displayed Visceral hypersensitivity accompanied by increases in Toll-like receptor and cytokine gene expression in the spinal cord, which were normalized by postnatal colonization with microbiota from conventionally colonized (CC). In GF mice, the volumes of the anterior cingulate cortex (ACC) and periaqueductal grey, areas involved in Pain processing, were decreased and enlarged, respectively, and dendritic changes in the ACC were evident. These findings indicate that the gut microbiota is required for the normal Visceral Pain sensation.
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the gut microbiota as a key regulator of Visceral Pain
Pain, 2017Co-Authors: Siobhain M O Mahony, Timothy G Dinan, John F CryanAbstract:1. Visceral PainVisceral Pain can range from the discomfort of indigestion to the excruciating Pain of renal colic.19 Irritable bowel syndrome (IBS) is a complex and heterogeneous disorder with exaggerated Visceral Pain as a major distinguishing feature.44 Other Visceral Pain–related disorders inclu
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stress and the microbiota gut brain axis in Visceral Pain relevance to irritable bowel syndrome
CNS Neuroscience & Therapeutics, 2016Co-Authors: Rachel D. Moloney, Timothy G Dinan, Siobhain M Omahony, Anthony C Johnson, Beverley Greenwoodvan Meerveld, John F CryanAbstract:Visceral Pain is a global term used to describe Pain originating from the internal organs of the body, which affects a significant proportion of the population and is a common feature of functional gastrointestinal disorders (FGIDs) such as irritable bowel syndrome (IBS). While IBS is multifactorial, with no single etiology to completely explain the disorder, many patients also experience comorbid behavioral disorders, such as anxiety or depression; thus, IBS is described as a disorder of the gut-brain axis. Stress is implicated in the development and exacerbation of Visceral Pain disorders. Chronic stress can modify central Pain circuitry, as well as change motility and permeability throughout the gastrointestinal (GI) tract. More recently, the role of the gut microbiota in the bidirectional communication along the gut-brain axis, and subsequent changes in behavior, has emerged. Thus, stress and the gut microbiota can interact through complementary or opposing factors to influence Visceral nociceptive behaviors. This review will highlight the evidence by which stress and the gut microbiota interact in the regulation of Visceral nociception. We will focus on the influence of stress on the microbiota and the mechanisms by which microbiota can affect the stress response and behavioral outcomes with an emphasis on Visceral Pain.
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Stress-induced Visceral Pain: toward animal models of irritable-bowel syndrome and associated comorbidities.
Frontiers in Psychiatry, 2015Co-Authors: Rachel D. Moloney, Timothy G Dinan, Siobhain M. O'mahony, John F CryanAbstract:Visceral Pain is a global term used to describe Pain originating from the internal organs, which is distinct from somatic Pain. It is a hallmark of functional gastrointestinal disorders such as irritable bowel syndrome (IBS). Currently the treatment strategies targeting Visceral Pain are unsatisfactory, with development of novel therapeutics hindered by a lack of detailed knowledge of the underlying mechanisms. Stress has long been implicated in the pathophysiology of Visceral Pain in both preclinical and clinical studies. Here we discuss the complex aetiology of Visceral Pain reviewing our current understanding in the context of the role of stress, gender, gut microbiota alterations, and immune functioning. Furthermore we review the role of glutamate, GABA, and epigenetic mechanisms as possible therapeutic strategies for the treatment of Visceral Pain for which there is an unmet medical need. Moreover we discuss the most widely described rodent models used to model Visceral Pain in the preclinical setting. The theory behind, and application of, animal models is key for both the understanding of underlying mechanisms and design of future therapeutic interventions. Taken together, it is apparent that stress-induced Visceral Pain and it’s psychiatric co-morbidities, as typified by IBS, has a multifaceted aetiology. Moreover, treatment strategies still lag far behind when compared to other Pain modalities. The development of novel, effective and specific therapeutics for the treatment of Visceral Pain has never been more pertinent.
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toll like receptor 4 regulates chronic stress induced Visceral Pain in mice
Biological Psychiatry, 2014Co-Authors: Monica Tramullas, Timothy G Dinan, Rachel D. Moloney, Beate C Finger, Anna V Golubeva, Gerard M Moloney, John F CryanAbstract:Background Functional gastrointestinal disorders, which have Visceral hypersensitivity as a core symptom, are frequently comorbid with stress-related psychiatric disorders. Increasing evidence points to a key role for toll-like receptor 4 (TLR4) in chronic Pain states of somatic origin. However, the central contribution of TLR4 in Visceral Pain sensation remains elusive. Methods With pharmacological and genetic approaches, we investigated the involvement of TLR4 in the modulation of Visceral Pain. The TLR4-deficient and wild-type mice were exposed to chronic stress. Visceral Pain was evaluated with colorectal distension. Protein expression levels for TLR4, Cd11b, and glial fibrillary acidic protein (glial cells markers) were quantified in the lumbar region of the spinal cord, prefrontal cortex (PFC), and hippocampus. To evaluate the effect of blocking TLR4 on Visceral nociception, TAK-242, a selective TLR4 antagonist, was administered peripherally (intravenous) and centrally (intracerebroventricular and intra-PFC) ( n = 10–12/experimental group). Results The TLR4 deficiency reduced Visceral Pain and prevented the development of chronic psychosocial stress-induced Visceral hypersensitivity. Increased expression of TLR4 coupled with enhanced glia activation in the PFC and increased levels of proinflammatory cytokines were observed after chronic stress in wild-type mice. Administration of a TLR4 specific antagonist, TAK-242, attenuated Visceral Pain sensation in animals with functional TLR4 when administrated centrally and peripherally. Moreover, intra-PFC TAK-242 administration also counteracted chronic stress-induced Visceral hypersensitivity. Conclusions Our results reveal a novel role for TLR4 within the PFC in the modulation of Visceral nociception and point to TLR4 as a potential therapeutic target for the development of drugs to treat Visceral hypersensitivity.
