Upregulation of LENK and VIP in paracervical ganglion neurons supplying the urinary bladder of tetrodotoxin- and resiniferatoxin-treated female pigs

2012 ◽  
Vol 60 (3) ◽  
pp. 383-393 ◽  
Author(s):  
Piotr Burliński ◽  
Agnieszka Czujkowska ◽  
Marcin Arciszewski ◽  
Jarosław Całka

Both resiniferatoxin (RTX) and tetrodotoxin (TTX) have been reported to be effective in several clinical trials aiming to cure urinary bladder dysfunction. The goal of this experiment was to study the effect of intravesical administration of RTX and TTX on the chemical coding of paracervical ganglion (PCG) neurons that supply the urinary bladder in pigs. The vasoactive intestinal peptide (VIP) and the opioid family member Leu5-enkephalin (LENK) are both known for their regulatory effects in the function of the porcine genitourinary tract. The PCG neurons innervating the urinary bladder were identified by application of the retrograde tracer Fast Blue (FB), injected into the bladder wall prior to intravesical RTX or TTX administration. Immunocytochemical detection of LENK and VIP expression in the FB-labelled perikarya revealed that in the control group 25.15% of the FB-positive PCG neurons contained LENK, and 9.22% of them expressed VIP. Intravesical infusion of RTX resulted in an increase in the number of LENKIR neurons to 48.19% and VIP-IR perikarya to 11.25%. Optional treatment with TTX induced increase of LENK-IR neurons up to 81.67% and VIP-IR population to 16.46% of the FB-positive PCG cells. The present results show that both neurotoxins affect the chemical coding of PCG nervous cells supplying the porcine urinary bladder and that they stimulate both LENK and VIP expression. Furthermore, the results indicate a possible involvement of LENK and VIP neurons in the mechanisms of action of RTX and TTX in the therapy of overactive bladder disorder.

2011 ◽  
Vol 59 (4) ◽  
pp. 455-463 ◽  
Author(s):  
Piotr Burliński ◽  
Sławomir Gonkowski ◽  
Jarosław Całka

The aim of the present study was to establish the effect of intravesical administration of resiniferatoxin (RTX) and tetrodotoxin (TTX) on the chemical coding of paracervical ganglion (PCG) neurons supplying the urinary bladder in the pig. In order to identify the PCG neurons innervating the bladder, retrograde tracer Fast Blue was injected into the bladder wall prior to intravesical RTX or TTX administration. Consequent application of immunocytochemical methods revealed that in the control group 76.82% of Fast Blue positive PCG neurons contain nitric oxide synthetase (nNOS), and 66.92% contain acetylcholine transferase (ChAT). Intravesical infusion of RTX resulted in a reduction of the nNOS-IR neurons to 57.74% and ChAT-IR to 57.05%. Alternative administration of TTX induced an increase of nNOS-IR neurons up to 79.29% and a reduction of the ChAT-IR population down to 3.73% of the Fast Blue positive PCG cells. Our data show that both neurotoxins affect the chemical coding of PCG cells supplying the porcine urinary bladder, but the effects of their action are different. Moreover, these results shed light on the possible involvement of NO-ergic and cholinergic neurons in the mechanisms of therapeutic action exerted by RTX and TTX in curing the overactive bladder disorder.


2012 ◽  
Vol 15 (1) ◽  
pp. 101-109 ◽  
Author(s):  
A. Bossowska ◽  
M. Majewski

Conantokin G-induced changes in the chemical coding of dorsal root ganglion neurons supplying the porcine urinary bladder Conantokin G (CTG), isolated from the venom of the marine cone snail Conus geographus, is an antagonist of N-methyl-d-aspartate receptors (NMDARs), the activation of which, especially those located on the central afferent terminals and dorsal horn neurons, leads to hypersensitivity and pain. Thus, CTG blocking of NMDARs, has an antinociceptive effect, particularly in the case of neurogenic pain treatment. As many urinary bladder disorders are caused by hyperactivity of sensory bladder innervation, it seems useful to estimate the influence of CTG on the plasticity of sensory neurons supplying the organ. Retrograde tracer Fast Blue (FB) was injected into the urinary bladder wall of six juvenile female pigs. Three weeks later, intramural bladder injections of CTG (120 μg per animal) were carried out in all animals. After a week, dorsal root ganglia of interest were harvested from all animals and neurochemical characterization of FB+ neurons was performed using a routine double-immunofluorescence labeling technique on 10-μm-thick cryostat sections. CTG injections led to a significant decrease in the number of FB+ neurons containing substance P (SP), pituitary adenylate cyclase activating polypeptide (PACAP), somatostatin (SOM), calbindin (CB) and nitric oxide synthase (NOS) when compared with healthy animals (20% vs. 45%, 13% vs. 26%, 1.3% vs. 3%, 1.2 vs. 4% and 0.9% vs. 6% respectively) and to an increase in the number of cells immunolabelled for galanin (GAL, 39% vs. 6.5%). These data demonstrated that CTG changed the chemical coding of bladder sensory neurons, thus indicating that CTG could eventually be used in the therapy of selected neurogenic bladder illnesses.


2021 ◽  
Vol 22 (24) ◽  
pp. 13399
Author(s):  
Paweł Janikiewicz ◽  
Barbara Wasilewska ◽  
Urszula Mazur ◽  
Amelia Franke-Radowiecka ◽  
Mariusz Majewski ◽  
...  

Although guanethidine (GUA) was used in the past as a drug to suppress hyperactivity of the sympathetic nerve fibers, there are no available data concerning the possible action of this substance on the sensory component of the peripheral nervous system supplying the urinary bladder. Thus, the present study was aimed at disclosing the influence of intravesically instilled GUA on the distribution, relative frequency, and chemical coding of dorsal root ganglion neurons associated with the porcine urinary bladder. The investigated sensory neurons were visualized with a retrograde tracing method using Fast Blue (FB), while their chemical profile was disclosed with single-labeling immunohistochemistry using antibodies against substance P (SP), calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase activating polypeptide (PACAP), galanin (GAL), neuronal nitric oxide synthase (nNOS), somatostatin (SOM), and calbindin (CB). After GUA treatment, a slight decrease in the number of FB+ neurons containing SP was observed when compared with untreated animals (34.6 ± 6.5% vs. 45.6 ± 1.3%), while the number of retrogradely traced cells immunolabeled for GAL, nNOS, and CB distinctly increased (12.3 ± 1.0% vs. 7.4 ± 0.6%, 11.9 ± 0.6% vs. 5.4 ± 0.5% and 8.6 ± 0.5% vs. 2.7 ± 0.4%, respectively). However, administration of GUA did not change the number of FB+ neurons containing CGRP, PACAP, or SOM. The present study provides evidence that GUA significantly modifies the sensory innervation of the porcine urinary bladder wall and thus may be considered a potential tool for studying the plasticity of this subdivision of the bladder innervation.


2002 ◽  
Vol 41 (3) ◽  
pp. 234-239 ◽  
Author(s):  
Mark Goepel ◽  
Josef A. Hoffmann ◽  
Maria Piro ◽  
Herbert Rübben ◽  
Martin C. Michel

Author(s):  
B. Suryaprakash ◽  
M. S. Rao ◽  
S. K. Thind ◽  
S. Faidyanathan ◽  
A. K. Goel

2020 ◽  
Vol 29 (9) ◽  
pp. S23-S26 ◽  
Author(s):  
Frances Harries

Sacral neuromodulation is an internationally endorsed therapy recognised by the National Institute for Health and Care Excellence for patients who have refractory overactive bladder symptoms and/or idiopathic non-obstructive urinary retention when conservative treatments have failed or when patients have been unable to tolerate them. The Medtronic InterStim System used at the Queen Elizabeth Hospital Birmingham received CE mark approval in 1995 for bladder indications. To date, over 300 000 patients worldwide have been treated, with 61–90% reporting satisfaction with treatment ( Sutherland et al, 2007 ; Leong et al, 2011 ). It is a safe and effective intervention that can positively impact upon the management of both of these conditions, in particular overactive bladder. This highly prevalent condition is distressing to the individual and has an economic burden to society comparable in magnitude with that of breast cancer and osteoporosis ( Hu and Wagner, 2005 ).


Life Sciences ◽  
2018 ◽  
Vol 193 ◽  
pp. 207-213 ◽  
Author(s):  
Bizhan R. Sharopov ◽  
Kseniya L. Gulak ◽  
Igor B. Philyppov ◽  
Anna V. Sotkis ◽  
Yaroslav M. Shuba

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