scholarly journals Cystitis increases colorectal afferent sensitivity in the mouse

2009 ◽  
Vol 297 (6) ◽  
pp. G1250-G1258 ◽  
Author(s):  
Pablo Rodolfo Brumovsky ◽  
Bin Feng ◽  
Linjing Xu ◽  
Carly Jane McCarthy ◽  
G. F. Gebhart
Keyword(s):  
Urinary Bladder ◽  
Treated Group ◽  
Mechanical Sensitivity ◽  
Pelvic Nerve ◽  
Treatment Groups ◽  
Colon Inflammation ◽  
Afferent Fibers ◽  
Peripheral Mechanism ◽  
Inflammatory Soup

Studies in humans and rodents suggest that colon inflammation promotes urinary bladder hypersensitivity and, conversely, that cystitis contributes to colon hypersensitivity, events referred to as cross-organ sensitization. To investigate a potential peripheral mechanism, we examined whether cystitis alters the sensitivity of pelvic nerve colorectal afferents. Male C57BL/6 mice were treated with cyclophosphamide (CYP) or saline, and the mechanosensitive properties of single afferent fibers innervating the colorectum were studied with an in vitro preparation. In addition, mechanosensitive receptive endings were exposed to an inflammatory soup (IS) to study sensitization. Urinary bladder mechanosensitive afferents were also tested. We found that baseline responses of stretch-sensitive colorectal afferents did not differ between treatment groups. Whereas IS excited a proportion of colorectal afferents CYP treatment did not alter the magnitude of this response. However, the number of stretch-sensitive fibers excited by IS was increased relative to saline-treated mice. Responses to IS were not altered by CYP treatment, but the proportion of IS-responsive fibers was increased relative to saline-treated mice. In bladder, IS application increased responses of muscular afferents to stretch, although no differences were detected between saline- and CYP-treated mice. In contrast, their chemosensitivity to IS was decreased in the CYP-treated group. Histological examination revealed no changes in colorectum and modest edema and infiltration in the urinary bladder of CYP-treated mice. In conclusion, CYP treatment increased mechanical sensitivity of colorectal muscular afferents and increased the proportion of chemosensitive colorectal afferents. These data support a peripheral contribution to cross-organ sensitization of pelvic organs.

Hydroxyl Safflower Yellow Pigment A (HSYA) Improves Vascular Endothelial Injury Induced by Lipopolysaccharide In Vitro Study

2021 ◽  
Vol 11 (9) ◽  
pp. 1792-1798
Author(s):  
Li Yan ◽  
Ge Jingping ◽  
Yin Yuanyuan ◽  
Li Xiaomei ◽  
Zhao Boxiang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
In Vitro Study ◽  
Treated Group ◽  
Yellow Pigment ◽  
Endothelial Injury ◽  
Vitro Study ◽  
Vascular Endothelial ◽  
Treatment Groups ◽  
Dose Dependent

Aim: This research was to investigate the effects and mechanisms of HSYA in vascular endothelial injury by vitro study. Methods: Dividing HUVECs as Normal Control (NC), Model (LPS treated) group, HSYA-L, HSYA-M and HSYA-H groups. Cells in the HSYA treatment groups were treated with LPS, followed by 40 mg/ml, 80 mg/ml, and 120 mg/ml HSYA intervention (HSYA-L, HSYA-M, and HSYA -H groups), respectively. Measuring the cell proliferation, apoptosis, relative proteins and mRNA (TLR4, MyD88 and NF-κB(p65)) expressions by MTT, Flow cytometry, WB and RT-qPCR assay. Using cellular immunofluorescence to evaluate NF-κB(p65) nuclear volume of difference groups. Results: With HSYA supplement, the cell proliferation rates were significantly up-regulation with cell apoptosis significantly down-regulation with TLR4 relatived mRNA and proteins and NF-κB(p65) nuclear significantly depressed with dose-dependent (P <0.05, respectively). Conclusion: HSYA improved vascular endothelial injury induced by LPS via TLR4 pathway In Vitro.

Mechanosensitive Pelvic Nerve Afferent Fibers Innervating the Colon of the Rat are Polymodal in Character

1998 ◽  
Vol 80 (5) ◽  
pp. 2632-2644 ◽  
Author(s):  
X. Su ◽  
G. F. Gebhart
Keyword(s):  
Bile Salts ◽  
Thermal Sensitivity ◽  
Muscle Tension ◽  
Dependent Manner ◽  
Krebs Solution ◽  
Pelvic Nerve ◽  
Afferent Fibers ◽  
Inflammatory Soup ◽  
Resting Activity ◽  
Thermal Stimuli

Su, X. and G. F. Gebhart. Mechanosensitive pelvic nerve afferent fibers innervating the colon of the rat are polymodal in character. J. Neurophysiol. 80: 00–00, 1998. This report describes the chemical and thermal sensitivity of mechanosensitive pelvic nerve afferent fibers innervating the colon of the rat. A total of 51 fibers in the S1 dorsal root, identified by electrical stimulation of the pelvic nerve, were studied. An approximately 7 cm length of descending colon was isolated in situ to permit intracolonic perfusion and distension with Krebs solution. Reproducibility of responses to repetitive colorectal distension (CRD, 40 mmHg, 30 s, every 4 min) was documented. All fibers gave monotonic, incrementing responses to graded CRD (5 to 60 mmHg). Increases ( n = 6) or decreases ( n = 6) in pH of the perfusate failed to produce any change in resting activity or responses to CRD. Infusion of bile salts increased the resting activity of 6/6 fibers in a concentration-dependent manner, but did not affect the magnitude of responses to CRD. After intracolonic instillation of an inflammatory soup (bradykinin 10−5M, PGE210−5M, serotonin 10−5M, histamine 10−5M and KCl 10−3M), 13/22 fibers exhibited sensitization of responses to CRD. Seventy-three percent of 45 fibers tested responded to intracolonic perfusion of heated Krebs solution. The estimated threshold for response was 45°C and response magnitude increased with the temperature. A smaller proportion (30%) of 37 fibers tested responded to intracolonic perfusion of cold Krebs solution. The estimated threshold for response was 28°C. Of 36 fibers tested, 8 were activated by both heat and cold; typically, fibers activated by heat did not respond to cold. In a sample of 26 fibers tested for response to all three modalities of stimulation, 11 responded to mechanical, chemical and thermal stimuli; the remaining 15 responded to mechanical and either chemical or thermal stimulation. Changes in intracolonic pressure in response to chemical and thermal stimuli were also evaluated. Inflammatory soup and bile salts did not change intracolonic pressure; heat and cold produced a modest decrease and increase in muscle tension, respectively. These results document that mechanosensitive pelvic nerve afferent fibers are also chemosensitive and/or thermosensitive, supporting the notion that visceral mechanoreceptors in general are likely polymodal in character.

scholarly journals Bugs and drugs: a systems biology approach to characterising the effect of moxidectin on the horse’s faecal microbiome

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
S. P. Daniels ◽  
J. Leng ◽  
J. R. Swann ◽  
C. J. Proudman
Keyword(s):  
Gut Microbiota ◽  
Treated Group ◽  
Anthelmintic Treatment ◽  
Metabolic Profiles ◽  
Faecal Microbiota ◽  
Treatment Groups ◽  
Fermentation Kinetics ◽  
And Control

Abstract Background Anthelmintic treatment is a risk factor for intestinal disease in the horse, known as colic. However the mechanisms involved in the onset of disease post anthelmintic treatment are unknown. The interaction between anthelmintic drugs and the gut microbiota may be associated with this observed increase in risk of colic. Little is known about the interaction between gut microbiota and anthelmintics and how treatment may alter microbiome function. The objectives of this study were: To characterise (1) faecal microbiota, (2) feed fermentation kinetics in vitro and (3) metabolic profiles following moxidectin administration to horses with very low (0 epg) adult strongyle burdens. Hypothesis: Moxidectin will not alter (1) faecal microbiota, (2) feed fermentation in vitro, or, (3) host metabolome. Results Moxidectin increased the relative abundance of Deferribacter spp. and Spirochaetes spp. observed after 160 h in moxidectin treated horses. Reduced in vitro fibre fermentation was observed 16 h following moxidectin administration in vivo (P = 0.001), along with lower pH in the in vitro fermentations from the moxidectin treated group. Metabolic profiles from urine samples did not differ between the treatment groups. However metabolic profiles from in vitro fermentations differed between moxidectin and control groups 16 h after treatment (R2 = 0.69, Q2Y = 0.48), and within the moxidectin group between 16 h and 160 h post moxidectin treatment (R2 = 0.79, Q2Y = 0.77). Metabolic profiles from in vitro fermentations and fermentation kinetics both indicated altered carbohydrate metabolism following in vivo treatment with moxidectin. Conclusions These data suggest that in horses with low parasite burdens moxidectin had a small but measurable effect on both the community structure and the function of the gut microbiome.

Effects of Opioids on Mechanosensitive Pelvic Nerve Afferent Fibers Innervating the Urinary Bladder of the Rat

1997 ◽  
Vol 77 (3) ◽  
pp. 1566-1580 ◽  
Author(s):  
X. Su ◽  
J. N. Sengupta ◽  
G. F. Gebhart
Keyword(s):  
Urinary Bladder ◽  
Opioid Receptor ◽  
Dorsal Root ◽  
Mustard Oil ◽  
Pelvic Nerve ◽  
Receptor Agonists ◽  
C Fibers ◽  
Afferent Fibers ◽  
Δ Opioid Receptor ◽  
Opioid Receptor Agonists

Su, X., J. N. Sengupta, and G. F. Gebhart. Effects of opioids on mechanosensitive pelvic nerve afferent fibers innervating the urinary bladder of the rat. J. Neurophysiol. 77: 1566–1580, 1997. A total of 443 pelvic nerve afferent fibers in the L6 dorsal root of the rat were identified by electrical stimulation of the pelvic nerve; 319 (72%) were myelinated Aδ fibers with a mean conduction velocity (CV) of 11.8 m/s and 124 (28%) were unmyelinated C fibers with mean CV of 1.9 m/s. Two hundred fifty-two fibers (57%) responded to noxious urinary bladder distension (UBD; 80 mmHg); 108 were C fibers (mean CV: 1.9 m/s) and 144 were Aδ fibers (mean CV: 8.2 m/s). Forty-nine UBD-sensitive fibers were further characterized; all gave monotonic increases in firing to increasing distending pressures. Thirty-six fibers (73%) had a low-threshold (LT) for response (mean: 6 mmHg) and 13 fibers (27%) had high-thresholds (HT) for response (mean: 32 mmHg). Responses of 15 fibers to graded UBD (11 LT and 4 HT) were tested before and after instillation of 0.5 ml of 30% xylenes ( n = 11) or 5% mustard oil ( n = 4) into the bladder. The mean resting activity of 13 fibers significantly increased, and 7 fibers exhibited sensitization of responses to graded UBD 30 min after xylenes or mustard oil instillation. All 4 HT fibers were sensitized; 3 of the 11 LT fibers were sensitized (i.e., gave increased responses to UBD). The effects of opioid receptor agonists were tested on responses to noxious UBD (80 mmHg). Cumulative intraaterial doses of μ-opioid receptor agonists (morphine, 8 mg/kg, and fentanyl, 300 μg/kg) and of δ-opioid receptor agonists (DPDPE, 300 μg/kg, and SNC-80, 300 μg/kg) did not affect responses to noxious UBD. In contrast, cumulative 16 mg/kg intraarterial doses of the κ-opioid receptor agonists U50,488H, U69,593 and U62,066 dose-dependently attenuated responses to noxious UBD. There were no differences in the dose-response relationships of these drugs on afferent fibers from untreated and xylenes- or mustard oil-treated urinary bladder. These results reveal that there is a greater proportion of UBD-sensitive fibers in the L6 dorsal root (57%) than in the S1 dorsal root of the rat (38%; a previous study). The attenuation of responses to UBD by κ, but not μ or δ opioid receptor agonists suggests a potential use for peripherally acting κ opioid receptor agonists in the control of urinary bladder pain.

The influence of doxazosin, an α1-adrenergic receptor antagonist on the urinary bladder contractility in pigs

2014 ◽  
Vol 17 (3) ◽  
pp. 527-529 ◽  
Author(s):  
W. Markiewicz ◽  
A. Jasiecka ◽  
D. Barski ◽  
J. Janiuk ◽  
A. Bossowska ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Adrenergic Receptor ◽  
Treated Group ◽  
Control Group ◽  
Detrusor Smooth Muscle ◽  
Before And After ◽  
Term Administration

Abstract In the present study influence of doxazosin on the porcine urinary bladder contractility has been examined. Immature pigs were treated for 30 days with: a) doxazosin (n = 5) per os at a dose of 0.1 mg/kg b.w. or b) placebo (n = 5; control group). Thereafter, animals were sacrificed and urinary bladder strips from the trigone were suspended in organ baths. The tension of the smooth musce was measured before and after exposition to acetylocholine (ACh; 10-5 - 10-3 M), norepinephrine (NE; 10-9 - 10-7 M) and 5-hydroxytryptamine (5-HT; 10-7 - 10-5 M). Both the ACh and 5-HT at the highest doses significantly increased the contractility in each group, but this response was weaker in doxazosin-treated animals. NE caused relaxation in both groups, but the effect was weaker in doxazosine-treated group. The results of our study have shown that long-term administration of doxazosin caused a desensitization of the detrusor smooth muscle for in vitro applied mediators of the autonomic nervous systems.

Sensory Fibers of the Pelvic Nerve Innervating the Rat's Urinary Bladder

2000 ◽  
Vol 84 (4) ◽  
pp. 1924-1933 ◽  
Author(s):  
V. K. Shea ◽  
R. Cai ◽  
B. Crepps ◽  
J. L. Mason ◽  
E. R. Perl
Keyword(s):  
Urinary Bladder ◽  
Conduction Velocity ◽  
Receptive Fields ◽  
The Body ◽  
Sensory Innervation ◽  
Pelvic Nerve ◽  
Ureterovesical Junction ◽  
Bladder Filling ◽  
Afferent Fibers ◽  
Conduction Velocities

Much attention has been given to the pelvic nerve afferent innervation of the urinary bladder; however, reports differ considerably in descriptions of afferent receptor types, their conduction velocities, and their potential roles in bladder reflexes and sensation. The present study was undertaken to do a relatively unbiased sampling of bladder afferent fibers of the pelvic nerve in adult female rats. The search stimulus for units to be studied was electrical stimulation of both the bladder nerves and the pelvic nerve. Single-unit activity of 100 L6 dorsal root fibers, activated by both pelvic and bladder nerve stimulation, was analyzed. Sixty-five units had C-fiber and 35 units had Aδ-fiber conduction velocities. Receptive characteristics were established by direct mechanical stimulation, filling of the bladder with 0.9% NaCl at a physiological speed and by filling the bladder with solutions containing capsaicin, potassium, or turpentine oil. The majority (61) of these fibers were unambiguously excited by bladder filling with 0.9% NaCl and were classified as mechanoreceptors. All mechanoreceptors with receptive fields on the body of the bladder had low pressure thresholds (≤10 mmHg). Receptive fields of units with higher thresholds were near the ureterovesical junction, on the base of the bladder or could not be found. Neither thresholds nor suprathreshold responses could be related to conduction velocity. Bladder compliance and mechanoreceptor thresholds were influenced by the stage of the estrous cycle: both were lowest in proestrous rats and highest in metaestrous rats. Mechanoreceptors innervating the body of the bladder and the region near the ureterovesical junction showed two patterns of responsiveness to slow bladder filling. One group of units exhibited increasing activity with increasing pressure up to 40 mmHg, while the other group showed a peak in activity at pressures below 40 mmHg followed by a plateau or decrease in activity with increasing pressure. It is proposed that differences in stimulus transduction relate to the different response patterns. Thirty-nine units failed to respond to bladder filling. Eight of these were excited by intravesical potassium or capsaicin and were classified as chemoreceptors. The remaining 31 units were not excited by any stimulus tested. Chemoreceptors and unexcited units had both Aδ and C afferent fibers. We conclude that the pelvic nerve sensory innervation of the rat bladder is complex, may be sensitive to hormonal status, and that the properties of individual sensory receptors are not related in an obvious manner to the conduction velocity of their fibers.

scholarly journals Characterization of Mouse Lumbar Splanchnic and Pelvic Nerve Urinary Bladder Mechanosensory Afferents

2008 ◽  
Vol 99 (1) ◽  
pp. 244-253 ◽  
Author(s):  
Linjing Xu ◽  
G. F. Gebhart
Keyword(s):  
Spinal Cord ◽  
Urinary Bladder ◽  
Receptive Field ◽  
Present Report ◽  
Sensory Information ◽  
Total Sample ◽  
High Threshold ◽  
Mechanical Stimuli ◽  
Afferent Fibers

Sensory information from the urinary bladder is conveyed via lumbar splanchnic (LSN) and sacral pelvic (PN) nerves to the spinal cord. In the present report we compared the mechanosensitive properties of single afferent fibers in these two pathways using an in vitro mouse bladder preparation. Mechanosensitive primary afferents were recorded from the LSN or PN and distinguished based on their response to receptive field stimulation with different mechanical stimuli: probing (160 mg to 2 g), stretch (1–25 g), and stroking of the urothelium (10–1,000 mg). Four different classes of afferent were recorded from the LSN and PN: serosal, muscular, muscular/urothielial, and urothelial. The LSN contained principally serosal and muscular afferents (97% of the total sample), whereas all four afferent classes of afferent were present in the PN (63% of which were muscular afferents). In addition, the respective proportions and receptive field distributions differed between the two pathways. Both low- and high-threshold stretch-sensitive muscular afferents were present in both pathways, and muscular afferents in the PN were shown to sensitize after exposure to an inflammatory soup cocktail. The LSN and PN pathways contain different populations of mechanosensitive afferents capable of detecting a range of mechanical stimuli and individually tuned to detect the type, magnitude, and duration of the stimulus. This knowledge broadens our understanding of the potential roles these two pathways play in conveying mechanical information from the bladder to the spinal cord.

Mechanosensitive properties of pelvic nerve afferent fibers innervating the urinary bladder of the rat

1994 ◽  
Vol 72 (5) ◽  
pp. 2420-2430 ◽  
Author(s):  
J. N. Sengupta ◽  
G. F. Gebhart
Keyword(s):  
Acetic Acid ◽  
Urinary Bladder ◽  
Conduction Velocity ◽  
Regression Line ◽  
High Threshold ◽  
Pelvic Nerve ◽  
Distribution Profile ◽  
Stimulus Response ◽  
C Fibers ◽  
Afferent Fibers

1. Single-unit activity was recorded from S1 dorsal root afferent fibers in pentobarbital-anesthetized rats. In 25 experiments, 245 afferent fibers were identified by electrical stimulation of the pelvic nerve. Fifty-two percent were C fibers (conduction velocity: 1.70 +/- 0.04 m/s; mean +/- SE) and 48% were A delta-fibers (conduction velocity: 11.07 +/- 0.95 m/s). 2. Of 245 pelvic nerve afferent fibers, 92 (38%) responded to noxious urinary bladder distension (UBD; 80 mmHg); 57 of these fibers were C fibers and 35 were A delta-fibers. Forty-four fibers responded to colorectal distension (CRD; 80 mmHg); 32 were C fibers and 12 were A delta-fibers. A total of 39 fibers were identified in the anal mucosa; 3 were C fibers and 36 were A delta-fibers. Seventy fibers (28%) in these experiments were unresponsive to either UBD or CRD or to probing of the anal mucosa; 32 were unmyelinated C fibers and 38 were A delta-fibers. 3. Reproducibility of responses to repeated UBD (80 mmHg, 20 s; 8 trials at 4-min intervals) was tested in 10 fibers. In nine fibers, responses to repeated distension did not change; one fiber exhibited a progressive decrease in response magnitude after the third trial. 4. Of the 92 afferent fibers that responded to UBD, 45 were further characterized for responses to graded intensities of UBD. Forty fibers had some resting activity (1.7 +/- 0.3 impulses/s) and five fibers exhibited no ongoing activity. The response to UBD adapted slowly during the 20-s period of phasic UBD or during slow isotonic filling of the bladder. 5. The stimulus-response function (SRF) of fibers (n = 45) to graded UBD was monotonic < or = 80 mmHg. Thresholds for responses were determined after extrapolation of the least-squares linear regression line to the ordinate, and varied between 0 and 45 mmHg. The frequency distribution profile of thresholds revealed two populations of pelvic nerve afferent fibers in the urinary bladder: a larger group (n = 36) of low-threshold (LT) fibers (5.7 +/- 1.0 mmHg) and a smaller group (n = 9) of high-threshold (HT) fibers (34 +/- 2.5 mmHg). 6. Responses of four LT fibers to graded UBD were tested before and 30 min after instillation of 0.5 ml of 0.5% acetic acid (pH 3) into the bladder. The mean threshold for response of these fibers before instillation of acetic acid (9.4 +/- 3.1 mmHg) more than doubled (to 22.3 +/- 6.7 mmHg) after instillation of acetic acid.(ABSTRACT TRUNCATED AT 400 WORDS)

The influence of doxazosin on the contractility of the urinary bladder in female pigs with experimentally induced cystitis

2017 ◽  
Vol 20 (3) ◽  
pp. 485-490
Author(s):  
W. Markiewicz ◽  
A. Bossowska ◽  
E. Lepiarczyk ◽  
M. Majewski ◽  
P. Radziszewski ◽  
...  
Keyword(s):  
Body Weight ◽  
Urinary Bladder ◽  
Smooth Muscles ◽  
Treated Group ◽  
Control Group ◽  
Group I ◽  
Group Ii ◽  
Experimental Group ◽  
Experimentally Induced

Abstract The present in vitro study investigated the influence of doxazosin on the contractility of the urinary bladder in female pigs with experimentally induced cystitis. Fifteen juvenile female piglets (18-20 kg body weight) were randomly assigned into three groups (n=5 animals each): i) control (clinically healthy animals, without doxazosin treatment), ii) animals with induced inflammation of the urinary bladder, but without doxazosin treatment (experimental group I) and iii) animals with inflamed bladder, treated orally with doxazosin (0.1 mg/kg body weight for 30 days; experimental group II). Thereafter, the pigs were sacrificed and strips of the bladder trigone were suspended in organ baths. The tension and amplitude of the smooth muscles was measured before and after exposition to 5-hydroxytryptamine (5-HT; 10-6-10-4 M), acetylocholine (ACh; 10-5-10-3 M) and norepinephrine (NE; 10-9-10-7 M). 5-HT caused an increase in the tension of contractions in all the groups and the amplitude in the experimental groups, however, the effect was higher in the experimental group I than in group II as compared to that found in the pre-treatment period. ACh caused an increase in the tension in the control group and a decrease in the amplitude in both experimental groups; these changes significantly differed between the control and doxazosin-treated group. NE caused a decrease in the tension in both experimental groups and amplitude in all the groups, however, the effect was most strongly expressed in doxazosine-treated group. The present study has revealed that long-term administration of doxazosin causes a desensitization of the detrusor smooth muscle to in vitro applied mediators in the autonomic nervous system.

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