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Up-regulation of brain-derived neurotrophic factor in primary afferent pathway regulates colon-to-bladder cross-sensitization in rat.

Xia CM, Gulick MA, Yu SJ, Grider JR, Murthy KS, Kuemmerle JF, Akbarali HI, Qiao LY - J Neuroinflammation (2012)

Bottom Line: Colonic inflammation did not alter either the morphology of the urinary bladder or the expression level of TRPV1 in this viscus.However, colonic inflammation decreased the inter-micturition intervals and decreased the quantities of urine voided.Primary afferent-mediated BDNF up-regulation in the sensory neurons regulates, at least in part, the bladder activity during colonic inflammation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Virginia Commonwealth University School of Medicine, 1220 East Broad Street, PO Box 0551, MMRB 5038, VA 23219 Richmond, Virginia, USA.

ABSTRACT

Background: In humans, inflammation of either the urinary bladder or the distal colon often results in sensory cross-sensitization between these organs. Limited information is known about the mechanisms underlying this clinical syndrome. Studies with animal models have demonstrated that activation of primary afferent pathways may have a role in mediating viscero-visceral cross-organ sensitization.

Methods: Colonic inflammation was induced by a single dose of tri-nitrobenzene sulfonic acid (TNBS) instilled intracolonically. The histology of the colon and the urinary bladder was examined by hematoxylin and eosin (H&E) stain. The protein expression of transient receptor potential (TRP) ion channel of the vanilloid type 1 (TRPV1) and brain-derived neurotrophic factor (BDNF) were examined by immunohistochemistry and/or western blot. The inter-micturition intervals and the quantity of urine voided were obtained from analysis of cystometrograms.

Results: At 3 days post TNBS treatment, the protein level of TRPV1 was increased by 2-fold (p < 0.05) in the inflamed distal colon when examined with western blot. TRPV1 was mainly expressed in the axonal terminals in submucosal area of the distal colon, and was co-localized with the neural marker PGP9.5. In sensory neurons in the dorsal root ganglia (DRG), BDNF expression was augmented by colonic inflammation examined in the L1 DRG, and was expressed in TRPV1 positive neurons. The elevated level of BDNF in L1 DRG by colonic inflammation was blunted by prolonged pre-treatment of the animals with the neurotoxin resiniferatoxin (RTX). Colonic inflammation did not alter either the morphology of the urinary bladder or the expression level of TRPV1 in this viscus. However, colonic inflammation decreased the inter-micturition intervals and decreased the quantities of urine voided. The increased bladder activity by colonic inflammation was attenuated by prolonged intraluminal treatment with RTX or treatment with intrathecal BDNF neutralizing antibody.

Conclusion: Acute colonic inflammation increases bladder activity without affecting bladder morphology. Primary afferent-mediated BDNF up-regulation in the sensory neurons regulates, at least in part, the bladder activity during colonic inflammation.

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Cystometrograms in control animals and animals with colonic inflammation. The bladder inter-micturiton intervals (Aa and Ba) and the quantity of solution voided (Ab and Bb) were recorded in unrestrained conscious animals. The dotted vertical lines align the time points for urination, thus the distance between the dotted lines (or the peak of the micturition pressure) represents the inter-micturition intervals. Arrows indicate the non-voiding contractions (increases in the intravesicle pressure (Aa) but no voiding collected (Ab) corresponding to these urges).
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Figure 6: Cystometrograms in control animals and animals with colonic inflammation. The bladder inter-micturiton intervals (Aa and Ba) and the quantity of solution voided (Ab and Bb) were recorded in unrestrained conscious animals. The dotted vertical lines align the time points for urination, thus the distance between the dotted lines (or the peak of the micturition pressure) represents the inter-micturition intervals. Arrows indicate the non-voiding contractions (increases in the intravesicle pressure (Aa) but no voiding collected (Ab) corresponding to these urges).

Mentions: In conscious animals, colonic inflammation significantly decreased the micturition intervals when compared to control (control: 220.6 ± 12.1 seconds; TNBS: 81.2 6 ± 2.8 seconds; p < 0.01; Figure 6 and 7A). During colonic inflammation, animals also exhibited non-voiding contractions (arrows in Figure 6Aa), which were not seen in control animals (Figure 6Ba). To confirm the results, the micturition frequency was independently counted and calculated as 4.9 ± 0.3 times within a 1000-second time period prior to TNBS treatment. The micturition frequency was increased by 2.5-fold at day 3 post induction of colonic inflammation (Figure 7B). During micturition, the quantity of urine voided was weighed by a scale included in the system, and was automatically recorded by the program (Figure 6Ab, Bb). TNBS treatment significantly reduced the amount of each voiding (Figure 7C).


Up-regulation of brain-derived neurotrophic factor in primary afferent pathway regulates colon-to-bladder cross-sensitization in rat.

Xia CM, Gulick MA, Yu SJ, Grider JR, Murthy KS, Kuemmerle JF, Akbarali HI, Qiao LY - J Neuroinflammation (2012)

Cystometrograms in control animals and animals with colonic inflammation. The bladder inter-micturiton intervals (Aa and Ba) and the quantity of solution voided (Ab and Bb) were recorded in unrestrained conscious animals. The dotted vertical lines align the time points for urination, thus the distance between the dotted lines (or the peak of the micturition pressure) represents the inter-micturition intervals. Arrows indicate the non-voiding contractions (increases in the intravesicle pressure (Aa) but no voiding collected (Ab) corresponding to these urges).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3298724&req=5

Figure 6: Cystometrograms in control animals and animals with colonic inflammation. The bladder inter-micturiton intervals (Aa and Ba) and the quantity of solution voided (Ab and Bb) were recorded in unrestrained conscious animals. The dotted vertical lines align the time points for urination, thus the distance between the dotted lines (or the peak of the micturition pressure) represents the inter-micturition intervals. Arrows indicate the non-voiding contractions (increases in the intravesicle pressure (Aa) but no voiding collected (Ab) corresponding to these urges).
Mentions: In conscious animals, colonic inflammation significantly decreased the micturition intervals when compared to control (control: 220.6 ± 12.1 seconds; TNBS: 81.2 6 ± 2.8 seconds; p < 0.01; Figure 6 and 7A). During colonic inflammation, animals also exhibited non-voiding contractions (arrows in Figure 6Aa), which were not seen in control animals (Figure 6Ba). To confirm the results, the micturition frequency was independently counted and calculated as 4.9 ± 0.3 times within a 1000-second time period prior to TNBS treatment. The micturition frequency was increased by 2.5-fold at day 3 post induction of colonic inflammation (Figure 7B). During micturition, the quantity of urine voided was weighed by a scale included in the system, and was automatically recorded by the program (Figure 6Ab, Bb). TNBS treatment significantly reduced the amount of each voiding (Figure 7C).

Bottom Line: Colonic inflammation did not alter either the morphology of the urinary bladder or the expression level of TRPV1 in this viscus.However, colonic inflammation decreased the inter-micturition intervals and decreased the quantities of urine voided.Primary afferent-mediated BDNF up-regulation in the sensory neurons regulates, at least in part, the bladder activity during colonic inflammation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Virginia Commonwealth University School of Medicine, 1220 East Broad Street, PO Box 0551, MMRB 5038, VA 23219 Richmond, Virginia, USA.

ABSTRACT

Background: In humans, inflammation of either the urinary bladder or the distal colon often results in sensory cross-sensitization between these organs. Limited information is known about the mechanisms underlying this clinical syndrome. Studies with animal models have demonstrated that activation of primary afferent pathways may have a role in mediating viscero-visceral cross-organ sensitization.

Methods: Colonic inflammation was induced by a single dose of tri-nitrobenzene sulfonic acid (TNBS) instilled intracolonically. The histology of the colon and the urinary bladder was examined by hematoxylin and eosin (H&E) stain. The protein expression of transient receptor potential (TRP) ion channel of the vanilloid type 1 (TRPV1) and brain-derived neurotrophic factor (BDNF) were examined by immunohistochemistry and/or western blot. The inter-micturition intervals and the quantity of urine voided were obtained from analysis of cystometrograms.

Results: At 3 days post TNBS treatment, the protein level of TRPV1 was increased by 2-fold (p < 0.05) in the inflamed distal colon when examined with western blot. TRPV1 was mainly expressed in the axonal terminals in submucosal area of the distal colon, and was co-localized with the neural marker PGP9.5. In sensory neurons in the dorsal root ganglia (DRG), BDNF expression was augmented by colonic inflammation examined in the L1 DRG, and was expressed in TRPV1 positive neurons. The elevated level of BDNF in L1 DRG by colonic inflammation was blunted by prolonged pre-treatment of the animals with the neurotoxin resiniferatoxin (RTX). Colonic inflammation did not alter either the morphology of the urinary bladder or the expression level of TRPV1 in this viscus. However, colonic inflammation decreased the inter-micturition intervals and decreased the quantities of urine voided. The increased bladder activity by colonic inflammation was attenuated by prolonged intraluminal treatment with RTX or treatment with intrathecal BDNF neutralizing antibody.

Conclusion: Acute colonic inflammation increases bladder activity without affecting bladder morphology. Primary afferent-mediated BDNF up-regulation in the sensory neurons regulates, at least in part, the bladder activity during colonic inflammation.

Show MeSH
Related in: MedlinePlus