Visceromotor Reflex Research Articles

Protocolo diagnóstico y terapéutico de la flatulencia y la distensión abdominal recurrente

The sensation of abdominal bloating may be accompanied by the objectifiable sign of abdominal distension, which entails an increase in abdominal circumference. It is the most common digestive symptom and the second most common functional gastrointestinal disorder (FGID). Flatulence refers to the expulsion of excess and/or excessively foul-smelling gas through the rectum. There are no validated consensus guidelines for the diagnosis and treatment of abdominal distension. A good differential diagnosis is important. It should start with a comprehensive case history that provides guidance on its origin and allows for detecting alarm signs and ruling out underlying organic pathology. The study should be completed with additional tests guided by clinical suspicion and according to the severity of the case. In regard to treatment, targeted action can be taken when there is an organic cause. In its absence, it is necessary to focus on reducing factors that favor abdominal distension. There are hygienic and dietary recommendations, drug treatment, and visceromotor reflex reeducation.

Sexually Dimorphic Effects of Histamine Degradation by Enteric Glial Histamine N-Methyltransferase (HNMT) on Visceral Hypersensitivity.

Histamine is a neuromodulator that affects gut motility and visceral sensitivity through intrinsic and extrinsic neural pathways, yet the mechanisms regulating histamine availability in these pathways remain poorly understood. Here, we show that enteric glia contribute to histamine clearance in the enteric nervous system (ENS) through their expression of the enzyme histamine N-methyltransferase (HNMT). Glial HNMT expression was initially assessed using immunolabeling and gene expression, and functionally tested using CRISPR-Cas9 to create a Cre-dependent conditional Hnmt ablation model targeting glia. Immunolabeling, calcium imaging, and visceromotor reflex recordings were used to assess the effects on ENS structure and visceral hypersensitivity. Immunolabeling and gene expression data show that enteric neurons and glia express HNMT. Deleting Hnmt in Sox10+ enteric glia increased glial histamine levels and altered visceromotor responses to colorectal distension in male mice, with no effect in females. Interestingly, deleting glial Hnmt protected males from histamine-driven visceral hypersensitivity. These data uncover a significant role for glial HNMT in histamine degradation in the gut, which impacts histamine-driven visceral hypersensitivity in a sex-dependent manner. Changes in the capacity of glia to clear histamines could play a role in the susceptibility to developing visceral pain in disorders of the gut-brain interaction.

Spinal VGLUT3 lineage neurons drive visceral mechanical allodynia but not sensitized visceromotor reflexes

Visceral pain is among the most prevalent and bothersome forms of chronic pain, but their transmission in the spinal cord is still poorly understood. Here, we conducted focal colorectal distention (fCRD) to drive both visceromotor responses (VMRs) and aversion. We first found that spinal CCK neurons were necessary for noxious fCRD to drive both VMRs and aversion under naive conditions. We next showed that spinal VGLUT3 neurons mediate visceral allodynia, whose ablation caused loss of aversion evoked by low-intensity fCRD in mice with gastrointestinal (GI) inflammation or spinal circuit disinhibition. Importantly, these neurons were dispensable for driving sensitized VMRs under both inflammatory and central disinhibition conditions. Anatomically, a subset of VGLUT3 neurons projected to parabrachial nuclei, whose photoactivation sufficiently generated aversion in mice with GI inflammation, without influencing VMRs. Our studies suggest the presence of different spinal substrates that transmit nociceptive versus affective dimensions of visceral sensory information.

Рефлекторная взаимосвязь локомоторной и висцеральной систем человека

As a result of a review of literary sources and analysis of the information received, the relationship between internal organs and certain muscles was established. The physiological mechanism of viscero-motor reflexes is described.

Optimized Tibial Nerve Stimulation Partially Reduces Visceral Hypersensitivity in Rats Mediated via Autonomic and Opioid Mechanisms

The aim of this study was to investigate the therapeutic effect and possible mechanisms of tibial nerve stimulation (TNS) on visceral hypersensitivity in rats. 1) The effects of TNS with five sets of parameters on visceral sensitivity in normal rats were evaluated by the assessment of abdominal electromyogram (EMG) and abdominal withdrawal reflex (AWR). 2) The effects and mechanisms of TNS with a special set of parameters (14Hz, 330 μsec, and 40% motor threshold) were evaluated in acute visceral hypersensitivity rats induced by restraint stress and colonic hypersensitized rats induced by acetic acid during the neonatal stage assessed by the EMG, AWR, and the spectral analysis of heart rate variability derived from the electrocardiogram. 1) In normal rats, TNS did not show any effect on the visceromotor reflex. 2) In rats with restraint stress-induced hypersensitivity, TNS with the special set of parameters reduced AWR scores and EMG responses to rectal distention at a pressure of 20-60 mmHg (p < 0.05, vs. baseline for both AWR and EMG). Concurrently, TNS increased vagal activity and decreased sympathetic activity (p < 0.03 for both). 3) Similar effects were noted on the EMG (p < 0.05, vs. baseline) and AWR (p < 0.05 vs. baseline) with acute and chronic TNS in rats with chronic colonic hypersensitivity and the effects were blocked by naloxone. TNS with parameters of 14Hz, 330 μsec, and 40% motor threshold is effective in improving visceral hypersensitivity in rodent models of colonic hypersensitivity via the modulation of autonomic and opioid mechanisms.

Neuro-Immune Modulation Effects of Sacral Nerve Stimulation for Visceral Hypersensitivity in Rats.

Background: Visceral hypersensitivity (VH) is one of the underlying pathophysiologies of irritable bowel syndrome. Mast cell overactivation has been found to be one of the main causes of VH. We investigated the effects and mechanisms of actions of sacral nerve stimulation (SNS) on visceral pain in a rodent model of VH.Methods: The VH was established by an intrarectal infusion of AA in 10-day-old pups. Rats were chronically implanted with electrodes for SNS and recording electromyogram (EMG) and electrocardiogram. The acute study was performed in 2-randomized sessions with SNS (14 Hz, 330 μs, 40% motor threshold or MT, 30 min) or sham-SNS. Later on, rats were randomized into SNS/sham-SNS groups and a chronic study was performed with 2 h-daily SNS or sham-SNS for 21 days. Visceromotor reflexes were assessed by abdominal EMG and withdrawal reflex (AWR). Colon tissues were collected to study colonic acetylcholine (ACh), the enteric neurons (ChAT, nNOS, and PGP9.5), mast cells activity [Tryptase, prostaglandins E2 (PGE2), and cyclooxygenases-2 (COX2)] and pain markers [nerve growth factor (NGF) and Sub-P].Key Results: Sacral nerve stimulation significantly improved visceromotor reflexes assessed by the EMG and AWR, compared with sham-SNS. SNS normalized the protein expressions of ChAT and nNOS and regulated mast cells activity by downregulating Tryptase, COX2, and PGE2. Neonatal AA administration upregulated NGF and Sub-P; chronic SNS significantly decreased these pain biomarkers. Concurrently, chronic SNS increased ACh in colon tissues and vagal efferent activity.Conclusions: Sacral nerve stimulation reduces VH in rats and this ameliorating effect might be attributed to the suppression of mast cell overactivation in the colon tissue via the modulation of autonomic nervous system functions.

Enteric Glia Contribute to Visceral Hypersensitivity Through Interactions with Nociceptors

Enteric glia regulate gut motility, secretions, and neuroinflammation through intercellular signaling mechanisms that involve connexin‐43 (Cx43) hemichannels. Glial Cx43 signaling is active during the acute phase of colitis when the sensitization of nociceptors occurs, but how glia contribute to nociceptor sensitization is not known. Here, we tested the hypothesis that alterations to intercellular signaling between glia and nociceptors mediated by Cx43 contribute to the sensitization of nociceptors during gut inflammation. We used the dinitrobenzene sulfonic acid (DNBS) model of acute colitis and tested the effects on enteric glia using immunohistochemistry, multiplex immunoassays, and ethidium bromide dye uptake to measure glial Cx43 channel activity. Specific interactions between glia and nociceptors were assessed using the glial specific GFAP::hM3Dq DREADD mouse model in combination with visceromotor reflex recordings and pERK expression, and by directly recording nociceptor nerve fiber activity in TRPV1‐GCaMP5g‐tdT mice. DNBS colitis drove an increase in proinflammatory cytokines including IL6, TNFα, and IL17, and IL1β showed a 5‐fold increase (p&lt;0.05) at peak inflammation. Enteric glia contribute to IL1β production and immunolabeling data showed a 40% increase in glial IL1β (p&lt;0.05) that was confirmed by RNAseq data (2‐fold, p&lt;0.05). The pro‐inflammatory mediators IL1β, IL6, INFy, and TNFα increased glial dye uptake under basal conditions and IL1β and IL6 potentiated ADP‐stimulated dye uptake by 24% and 53%, respectively (p&lt;0.0001), in a Cx43‐dependent manner. The selective activation of glial cells with clozapine‐N‐oxide in GFAP::hM3Dq mice increased visceromotor responses to colorectal distensions (p&lt;0.05) and drove pERK expression in TRPV1+ sensory nerve fibers in the myenteric plexus. Neither IL1β nor glial activation alone significantly affected Ca2+ responses to capsaicin in TRPV1+ nerve fibers in the colon. However, glial activation in the presence of IL1β significantly potentiated nociceptor Ca2+ responses to capsaicin and this effect required signaling through Cx43 hemichannels. Our data show that enteric glia can affect the sensitivity visceral nociceptors in the context of inflammation through mechanisms that include the potentiation of glial Cx43 hemichannel function by IL1β and the subsequent sensitization of TRPV1 channels expressed by sensory neurons.Support or Funding InformationNational Institute of Health through NIDDK: R01DK103723, R01DK120862

Effect of chronic pretreatment with 17β-estradiol and/or progesterone on the nociceptive response to uterine cervical distension in a rat model

It is widely known that visceral pain is more prevalent in women than in men, and this phenomenon is interpreted as a consequence of the gonadal hormone modulation of pain perception and transduction. Uterine cervical distension might cause obstetric and gynecologic pain with clinical relevance to visceral pain. In this study, we focused on the roles of 17β-estradiol and progesterone in visceral nociception with the use of a rat model of uterine cervical distension. Female ovariectomized rats were injected with 17β-estradiol (E2) or progesterone (P4) for 21 days, after which visceral pain-induced spinal c-fos expression and visceromotor reflex changes were compared between ovariectomized and hormone-substituted groups. We found that uterine cervical distension induced a drastic increase in spinal c-fos expression and visceromotor reflex activity, and ovariectomy inhibited the increase in c-fos expression induced by visceral pain; this inhibition was reversed by estrogen but not progesterone replacement. This study demonstrates that estrogen is involved in uterine cervical nociception, while progesterone plays less of a significant role.

Spinal cord stimulation ameliorates detrusor over-activity and visceromotor pain responses in rats with cystitis.

Interstitial cystitis/painful bladder syndrome/(IC/PBS) results in recurring pain in the bladder and surrounding pelvic region caused by abnormal excitability of micturition reflexes. Spinal cord stimulation (SCS) is currently clinically used for the attenuation of neuropathic and visceral pain. The present study examined whether SCS at upper lumbar segments modulates detrusor overactivity and visceral hyperalgesia associated with cystitis in a rat model of cyclophosphamide (CYP)-induced cystitis. Cystitis was induced by intraperitoneal injection of CYP (200 mg/kg) in six adult female Sprague Dawley rats 48 h prior to urodynamic recordings. Another six rats served as-controls with saline injection. Cystometry and the external urethral sphincter (EUS) electromyography during bladder infusion were evaluated under urethane anesthesia. The visceromotor reflexes (VMR) obtained from the external abdominal oblique muscle were quantified during bladder infusion and isotonic bladder distension (IBD), respectively. After baseline recordings were taken, SCS was applied on the dorsal surface of L3 for 25 min. Urodynamic recordings and VMR during bladder infusion and IBD were repeated 2 h after SCS. CYP resulted in detrusor overactivity, stronger EUS tonic contractions, and increased VMR. SCS significantly reduced non-voiding contractions, prolonged EUS relaxation, and delayed VMR appearance during bladder infusion as well as significantly decreased VMR during IBD in cystitis rats. SCS improved bladder function and EUS relaxation during bladder infusion and significantly attenuated visceral nociceptive-related VMR during IBD in cystitis rats. SCS may have therapeutic potential for patients with hyperalgesia and IC/PBS.

Investigations of urethral sphincter activity in mice with bladder hyperalgesia before and after drug administration of gabapentin.

This study investigated the effect of gabapentin on lower urinary tract dysfunction focusing on urethral activities and cystitis-induced hyperalgesia in a mouse model of painful bladder syndrome/interstitial cystitis (PBS/IC). The electromyography(EMG) of external urethral sphincter(EUS) was difficult to obtain, but contained useful information to examine the drug effect in mice. Female C57BL/6J mice were intraperitoneally (ip) administration with either saline or 200mg/kg of cyclophosphamide (CYP) 48h before experimental evaluation. Cystitis mice were treated with administration of gabapentin (25 or 50mg/kg, ip). Cystometry and EUS EMG were obtained and analyzed during continuous bladder infusion. The visceral pain-related visceromotor reflex (VMR) was recorded in response to isotonic bladder distension. Cystitis mice showed shorter inter-contraction intervals and increased occurrence of non-voiding contractions during bladder infusion, with increased VMR during isotonic bladder distension, indicating cystitis-induced bladder hyperalgesia. Gabapentin (50mg/kg) suppressed effects of CYP on cystometry, but not on EUS EMG activity, during bladder infusion. The effect on urodynamic recordings lasted 4h. VMR was significantly reduced by gabapentin. The present study showed that CYP-induced cystitis in mice is a model of visceral hyperalgesia affecting detrusor contractions, not urethral activations. The technique of using EUSEMG to evaluate the drug effects on urethral activities is novel and useful for future investigations. Gabapentin can be as a potential treatment for detrusor overactivity and PBS/IC.

Abdominal skeletal muscle activity precedes spontaneous menstrual cramping pain in primary dysmenorrhea

Dysmenorrhea is a pervasive pain condition that affects 20-50% of reproductive-aged women. Distension of a visceral organ, such as the uterus, could elicit a visceromotor reflex, resulting in involuntary skeletal muscle activity and referred pain. Although referred abdominal pain mechanisms can contribute to visceral pain, the role of abdominal muscle activity has not yet been investigated within the context of menstrual pain. The goal of this study was to determine whether involuntary abdominal muscle activity precedes spontaneous episodes of menstrual cramping pain in dysmenorrheic women and whether naproxen administration affects abdominal muscle activity. Abdominal electromyography activity was recorded from women with severe dysmenorrhea (n= 38) and healthy controls (n= 10) during menses. Simultaneously, pain was measured in real time using a squeeze bulb or visual analog rheostat. Ninety minutes after naproxen administration, abdominal electromyography activity and menstrual pain were reassessed. As an additional control, women were also recorded off menses, and data were analyzed in relation to random bulb squeezes. Because it is unknown whether mechanisms of menstrual cramps are different in primary or secondary dysmenorrhea/chronic pelvic pain, the relationship between medical history and abdominal muscle activity was examined. To further examine differences in nociceptive mechanisms, pressure pain thresholds were also measured to evaluate changes in widespread pain sensitivity. Abdominal muscle activity related to random-bulb squeezing was rarely observed in healthy controls on menses (0.9 ± 0.6 episodes/hour) and in dysmenorrhea participants off menses (2.3 ± 0.6 episodes/hour). In dysmenorrheic participants during menses, abdominal muscle activity frequently preceded bulb squeezing indicative of menstrual cramping pain (10.8 ± 3.0 episodes/hour; P < .004). Whereas 45% of the women with dysmenorrhea (17 of 38) had episodes of abdominal muscle activity associated pain, only 13% (5 of 38) had episodes after naproxen (P= .011). Women with the abdominal muscle activity-associated pain were less likely to have a diagnosis for secondary dysmenorrhea or chronic pelvic pain (2 of 17) than women without this pain phenotype (10 of 21; P= .034). Similarly, women with the abdominal muscle activity-associated pain phenotype had less nonmenstrual pain days per month (0.6 ± 0.5) than women without the phenotype (12.4 ± 0.3; P= .002). Women with abdominal muscle activity-associated pain had pressure pain thresholds (22.4 ± 3.0 N) comparable with healthy controls (22.2 ± 3.0 N; P= .967). In contrast, women without abdominal muscle activity-associated pain had lower pressure pain thresholds (16.1± 1.9 N; P= .039). Abdominal muscle activity may contribute to cramping pain in primary dysmenorrhea but is resolvable with naproxen. Dysmenorrheic patients without cramp-associated abdominal muscle activity exhibit widespread pain sensitivity (lower pressure pain thresholds) and are more likely to also have a chronic pain diagnosis, suggesting their cramps are linked to changes in central pain processes. This preliminary study suggests new tools to phenotype menstrual pain and supports the hypothesis that multiple distinct mechanisms may contribute to dysmenorrhea.

The role of C-fibers in the development of chronic psychological stress induced enhanced bladder sensations and nociceptive responses: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome (MAPP) research network study.

To evaluate C fiber-mediated changes in bladder sensation and nociception in an animal model of stress induced bladder hyperalgesia and urinary frequency. Female Wistar-Kyoto (WKY) rats were exposed to a chronic (10 days) water avoidance stress (WAS) and compared to controls. Rats were evaluated by cystometrogram (CMG) and visceromotor reflex (VMR) to bladder infusion with room temperature (RT) or cold saline. Cold saline activates afferent C-fibers via cold bladder receptors. To further evaluate bladder hyperalgesia, CMG and VMR were also obtained during RT isometric bladder distention (RT-iBD) at variable pressures. During RT infusion, WAS rats had significant decreases in pressure threshold (PT) and in the ratio of VMR threshold/maximum intravesical pressure (IVPmax), and a significant increase in VMR duration. Cold infusion also induced significant decreases in PT and in the ratio of VMR threshold/IVPmax in WAS rats. During RT-iBD, rats exposed to WAS showed a significant decrease in VMR latency and a significant increase in VMR area under the curve (AUC) compared to controls. Chronic WAS induced bladder hypersensitivity manifested by earlier voiding with earlier VMR appearance. Chronic stress also enhanced bladder nociceptive responses. WAS leads to increase responses to ice cold water infusion, implying a role of sensitized C-fibers and mechanoreceptors in WAS-induced bladder dysfunction and hypersensitivity.

Serotonergic paraneurones in the female mouse urethral epithelium and their potential role in peripheral sensory information processing.

The mechanisms underlying detection and transmission of sensory signals arising from visceral organs, such as the urethra, are poorly understood. Recently, specialized ACh-expressing cells embedded in the urethral epithelium have been proposed as chemosensory sentinels for detection of bacterial infection. Here, we examined the morphology and potential role in sensory signalling of a different class of specialized cells that express serotonin (5-HT), termed paraneurones. Urethrae, dorsal root ganglia neurones and spinal cords were isolated from adult female mice and used for immunohistochemistry and calcium imaging. Visceromotor reflexes (VMRs) were recorded in vivo. We identified two morphologically distinct groups of 5-HT+ cells with distinct regional locations: bipolar-like cells predominant in the mid-urethra and multipolar-like cells predominant in the proximal and distal urethra. Sensory nerve fibres positive for calcitonin gene-related peptide, substance P, and TRPV1 were found in close proximity to 5-HT+ paraneurones. In vitro 5-HT (1 μm) stimulation of urethral primary afferent neurones, mimicking 5-HT release from paraneurones, elicited changes in the intracellular calcium concentration ([Ca2+ ]i ) mediated by 5-HT2 and 5-HT3 receptors. Approximately 50% of 5-HT responding cells also responded to capsaicin with changes in the [Ca2+ ]i . In vivo intra-urethral 5-HT application increased VMRs induced by urethral distention and activated pERK in lumbosacral spinal cord neurones. These morphological and functional findings provide insights into a putative paraneurone-neural network within the urethra that utilizes 5-HT signalling, presumably from paraneurones, to modulate primary sensory pathways carrying nociceptive and non-nociceptive (mechano-sensitive) information to the central nervous system.

Trypsin-protease activated receptor-2 signaling contributes to pancreatic cancer pain.

Pain treatment is a critical aspect of pancreatic cancer patient clinical care. This study investigated the role of trypsin-protease activated receptor-2 (PAR-2) in pancreatic cancer pain. Pancreatic tissue samples were collected from pancreatic cancer (n=22) and control patients (n=22). Immunofluorescence analyses confirmed colocalization of PAR-2 and neuronal markers in pancreatic cancer tissues. Trypsin levels and protease activities were higher in pancreatic cancer tissue specimens than in the controls. Supernatants from cultured human pancreatic cancer tissues (PC supernatants) induced substance P and calcitonin gene-related peptide release in dorsal root ganglia (DRG) neurons, and FS-NH2, a selective PAR-2 antagonist, inhibited this effect. A BALB/c nude mouse orthotopic tumor model was used to confirm the role of PAR-2 signaling in pancreatic cancer visceral pain, and male Sprague-Dawley rats were used to assess ambulatory pain. FS-NH2 treatment decreased hunch scores, mechanical hyperalgesia, and visceromotor reflex responses in tumor-bearing mice. In rats, subcutaneous injection of PC supernatant induced pain behavior, which was alleviated by treatment with FS-NH2 or FUT-175, a broad-spectrum serine protease inhibitor. Our findings suggest that trypsin-PAR-2 signaling contributes to pancreatic cancer pain in vivo. Treatment strategies targeting PAR-2 or its downstream signaling molecules might effectively relieve pancreatic cancer pain.

MP31-18 SPINAL CORD STIMULATION ATTENUATES VISCERAL PAIN-RELATED VISCEROMOTOR REFLEXES IN RODENTS WITH CYCLOPHOSPHAMIDE-INDUCED CYSTITIS

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I1 Apr 2017MP31-18 SPINAL CORD STIMULATION ATTENUATES VISCERAL PAIN-RELATED VISCEROMOTOR REFLEXES IN RODENTS WITH CYCLOPHOSPHAMIDE-INDUCED CYSTITIS Jih-Chao Yeh, David A Ginsberg, Larissa V Rodriguez, and Huiyi Harriet Chang Jih-Chao YehJih-Chao Yeh More articles by this author , David A GinsbergDavid A Ginsberg More articles by this author , Larissa V RodriguezLarissa V Rodriguez More articles by this author , and Huiyi Harriet ChangHuiyi Harriet Chang More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.972AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammation that results in recurring pain in the bladder and the surrounding pelvic region caused by abnormal excitability of micturition reflexes. Spinal cord stimulation (SCS) is currently in clinical use for the attenuation of neuropathic pain, and has been identified for amelioration of pain in a rodent model of colorectal distention. This study aimed to investigate the potential effect of SCS on attenuation of visceral pain-related visceromotor reflexes (VMR) in rodents with cyclophosphamide-induced cystitis. METHODS Female Sprague-Dawley rats underwent intraperitoneal injection of cyclophosphamide (CYP, n=8) or saline (controls, n=4). 48 hours after CYP or saline injections, all rats underwent surgical preparations under urethane anesthesia. Stimulation wires were placed on the dorsal surface of the spinal segments of L2 and L3 for SCS. A PE-50 tubing was inserted into the bladder to obtain the intravesical pressure (IVP). Two wires are placed in the left external abdominal oblique muscle to record VMR. Before and after SCS (40 Hz, 0.2 ms for 25 min), VMR and maximum intravesical pressure (IVPmax) were obtained during continuous bladder infusion and isotonic bladder distention (IBD). RESULTS During continuous bladder infusion (Fig 1A), the ratio of VMR threshold/IVPmax was significantly decreased in CYP rats indicating early VMR appearance compared to controls. SCS significantly increased the ratio indicating the delayed VMR appearance. During IBD with urethral occlusion, SCS delayed the latency of VMR appearance in CYP rats below the voiding thresholds at 10 and 20 cmH2O. SCS also significantly decreased VMR area under the curve (AUC) in CYP rats (Figs 1B-C). CONCLUSIONS SCS attenuated visceral pain-related VMR in rats with CYP-induced cystitis suggesting a role for SCS in modulating visceral nociception and hyperalgesia. SCS appears to be a potential treatment of IC/PBS. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e406 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Jih-Chao Yeh More articles by this author David A Ginsberg More articles by this author Larissa V Rodriguez More articles by this author Huiyi Harriet Chang More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

PD70-01 EFFECTS OF WATER AVOIDANCE STRESS ON PERIPHERAL AND CENTRAL RESPONSES DURING BLADDER FILLING IN THE RAT

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology III1 Apr 2017PD70-01 EFFECTS OF WATER AVOIDANCE STRESS ON PERIPHERAL AND CENTRAL RESPONSES DURING BLADDER FILLING IN THE RAT Huiyi Harriet Chang, Zhuo Wang, Yunliang Gao, Rong Zhang, Daniel P Holschneider, and Larissa V Rodriguez Huiyi Harriet ChangHuiyi Harriet Chang More articles by this author , Zhuo WangZhuo Wang More articles by this author , Yunliang GaoYunliang Gao More articles by this author , Rong ZhangRong Zhang More articles by this author , Daniel P HolschneiderDaniel P Holschneider More articles by this author , and Larissa V RodriguezLarissa V Rodriguez More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.3155AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Chronic emotional stress plays a role in the exacerbation and possibly the development of functional lower urinary tract disorders. Chronic water avoidance stress (WAS) in rodents is a model with high construct and face validity to bladder hypersensitivity syndromes, such as interstitial cystitis/bladder painful syndrome (IC/BPS), which manifest as urinary frequency and bladder hyperalgesia, which have been shown to be highly responsive to stress. Given the significant overlap of the brain circuits involved in stress, anxiety, and micturition, we evaluated the effects chronic stress has on bladder function and its effects on regional brain activation during bladder filling. METHODS 16 adult female Wistar-Kyoto rats were randomized to 10-day WAS (n=8) or handled controls (n=8). On day 11, rats were evaluated by visceromotor reflex (VMR) for bladder hyperalgesia. VMR was obtained during isotonic bladder distention (0-40 cmH2O) with urethral occlusion. Cerebral perfusion was assessed during bladder distention (20 cmH2O) using [14C]-iodoantipyrine autoradiography with regional cerebral blood flow-related tissue radioactivity (rCBF) analyzed in 3-D reconstructed brains with statistical parametric mapping. RESULTS At 20 cmH2O, VMR significantly increased in WAS compared to controls. WAS animals compared to controls showed greater activation in cortical regions of the central micturition circuit, with seed analysis showing increased functional connectivity of the cingulate to the parabrachial/Barrington nucleus complex (PBN), of the PBN to the thalamus and somatosensory and retrosplenial cortices, and of posterior insula to anterior secondary motor cortex. CONCLUSIONS The current study demonstrates how stress exacerbation of symptoms seen in the majority of patients with IC/PBS may be centrally mediated and gives us anatomic sites to further evaluate the biological mechanisms by which stress may induce or maintain bladder hyperalgesia and urinary frequency as well as a translational model to evaluate the molecular changes behind the brain differences seen in patients with IC/BPS. Collectively, our physiologic and brain mapping results suggest hypersensitivity during bladder filing in WAS animals, as well as increased engagement of portions of the micturition circuit responsive to urgency and the perception of bladder fullness, including viscerosensory perception and its relay to motor regions coordinating imminent bladder contractions. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1349 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Huiyi Harriet Chang More articles by this author Zhuo Wang More articles by this author Yunliang Gao More articles by this author Rong Zhang More articles by this author Daniel P Holschneider More articles by this author Larissa V Rodriguez More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats.

Estrogen receptor beta (ERβ) has been shown to play a therapeutic role in inflammatory bowel disease (IBD). However, the mechanism underlying how ERβ exerts therapeutic effects and its relationship with P2X3 receptors (P2X3R) in rats with inflammation is not known. In our study, animal behavior tests, visceromotor reflex recording, and Western blotting were used to determine whether the therapeutic effect of ERβ in rats with inflammation was related with P2X3R. In complete Freund adjuvant (CFA)-induced chronic inflammation in rats, paw withdrawal threshold was significantly decreased which were then reversed by systemic injection of ERβ agonists, DPN or ERB-041. In 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats, weight loss, higher DAI scores, increased visceromotor responses, and inflammatory responses were reversed by application of DPN or ERB-041. The higher expressions of P2X3R in dorsal root ganglia (DRG) of CFA-treated rats and those in rectocolon and DRG of TNBS-treated rats were all decreased by injection of DPN or ERB-041. DPN application also inhibited P2X3R-evoked inward currents in DRG neurons from TNBS rats. Mechanical hyperalgesia and increased P2X3 expression in ovariectomized (OVX) CFA-treated rats were reversed by estrogen replacements. Furthermore, the expressions of extracellular signal-regulated kinase (ERK) in DRG and spinal cord dorsal horn (SCDH) and c-fos in SCDH were significantly decreased after estrogen replacement compared with those of OVX rats. The ERK antagonist U0126 significantly reversed mechanical hyperalgesia in the OVX rats. These results suggest that estrogen may play an important therapeutic role in inflammation through down-regulation of P2X3R in peripheral tissues and the nervous system, probably via ERβ, suggesting a novel therapeutic strategy for clinical treatment of inflammation.

Effect of estrogen on visceral sensory function in a non-inflammatory colonic hypersensitivity rat model.

Increased prevalence of functional gastrointestinal disorders in women and perimenstrually accentuated symptoms imply that sexual hormones play a crucial role in the pathogenesis of such syndromes. The aim of this study was to analyze the selective effect of estrogen on visceral sensitivity in gonadectomized female and male Lewis rats with or without prior treatment with butyrate enemas. Following ovariectomy (OVX) or orchiectomy (ORX) estradiol pellets (E2-P) or sham pellets (Sham-P) were implanted. After treatment with butyrate (BUT) or saline (NaCl) enemas, colorectal distensions (CRD) were performed and the visceromotor reflex (VMR) to CRD was measured by electromyography. Gender did not influence VMR to CRD in gonadectomized animals. VMR in E2-P animals compared to Sham-P animals was increased (635 ± 32 μVs vs 470 ± 39 μVs; p = 0.002). Overall, instillation of butyrate enemas did not influence VMR to CRD. A comparison of CRD clusters showed that butyrate enemas in the E2-P animals resulted in a significant sensitization in both OVX and ORX animals. In female rats, sensitization was also caused by estrogen substitution alone. In our animal model, estrogen is a strong factor for an increase in visceral sensory function. Surprisingly, the treatment with butyrate alone did not evoke a general rise in VMR to CRD. Rats treated with butyrate enemas and under selective estrogen substitution developed visceral sensitization during the series of CRDs.

MP77-09 CHRONIC PSYCHOLOGICAL STRESS LEADS TO BLADDER HYRALGESIA VIA STRESS INDUCED SENSITIZATION OF C FIBERS AND MECHANORECPTORS

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction II1 Apr 2016MP77-09 CHRONIC PSYCHOLOGICAL STRESS LEADS TO BLADDER HYRALGESIA VIA STRESS INDUCED SENSITIZATION OF C FIBERS AND MECHANORECPTORS Yunliang Gao, Rong Zhang, Huiyi Chang, and Larissa Rodriguez Yunliang GaoYunliang Gao More articles by this author , Rong ZhangRong Zhang More articles by this author , Huiyi ChangHuiyi Chang More articles by this author , and Larissa RodriguezLarissa Rodriguez More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1923AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Patients affected by overactive bladder and painful bladder syndrome/interstitial cystitis report symptoms exacerbation when stressed. We have shown that anxiety prone animals exposed to chronic psychological water avoidance stress (WAS) develop sustained bladder hyperalgesia. The bladder cooling reflex (BCR) is a segmental reflex believed to be triggered by cold receptors in bladder wall with C fibers signaling. We aimed to evaluate the chronic stress induces changes in BCR and if C fiber sensitization contributes to stress-induced bladder hypersensitivity. METHODS 22 adult female Wistar-Kyoto rats equally divided to 10-day WAS or handled controls. On day 11, animals were evaluated by cystometrogram (CMG) as well as visceromotor reflex (VMR) for bladder sensitivity and pain to saline infusion. CMG and VMR were obtained during bladder infusion at room temperature (RT) and cold (4 degree C) with an open urethral outlet thus allowing the animal to void. CMG and VMR were also obtained during RT isotonic bladder distention (RT-IBD, 10-40 cmH2O) with urethral occlusion. RESULTS During RT infusion, WAS rats had a significant decreases in pressure threshold (PT) and the ratio of VMR threshold/maximum intravesical pressure (IVPmax). VMR duration significantly increased in WAS. BCR induced a more dramatic significant decline in PT and the ratio of VMR threshold/IVPmax in WAS (Fig.1A). No significant differences were found in contraction duration, inter-contraction interval or the VMR area under the curve (AUC) and duration. At RT-IBD (Fig.1B-C), VMR latency in WAS significantly decreased compared to controls. At 20 cmH2O, VMR AUC in WAS significantly increased compared to controls. CONCLUSIONS Chronic psychological stress induces bladder hypersensitivity, which manifests as earlier voiding and VMR. Prolonged VMR duration in WAS correlates with increased bladder sensitivity during voiding. BCR evokes C fibers activation and suggests that stress induced bladder hypersensitivity in functional voiding disorders mediated in part by afferent sensitization. Earlier VMR appearance at RT-IBD suggests a role for mechanoreceptor sensitivity in stress-induced bladder hypersensitivity. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1018-e1019 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Yunliang Gao More articles by this author Rong Zhang More articles by this author Huiyi Chang More articles by this author Larissa Rodriguez More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Миофасциальный синдром: от этиологии до терапии (обзор литературы)

Myofascial pain syndromes are rightly to enduring health problems. The authors emphasize that the etiology and pathogenesis of these conditions are reviewed with the &amp;#34;enviable&amp;#34; frequency. It is natural, it affects on the common principles of treatment and rehabilitation of this population. In this regard, the present review discuss current views on the pathogenesis, clinical manifestations and common principles of treatment of myofascial pain syndromes, mechanisms of action and features of the drug and non-drug methods used in the clinic vertebral neurology. The authors describe the principles of modern trends of manual therapy and reflexology. The review presents EMG and ultrasound methods for diagnosis of trigger points, the characteristics of local muscle hypertones: painful and not painful. Special attention is paid to such phenomena as dysfunctions of the temporomandibular joint and laryngeal-pharyngeal block, viscero-motor reflexes and posthistory syndrome.