Urine storage mechanisms

2012

Tetrodotoxin (TTX) mode of action is based on a blocking of fast sodium channels in nerve cell membrane what, in turn, abolishes the propagation of the action potential along the nerve fibers. TTX is currently used in experimental therapies focused on neoplastic or neurogenic pain, however, as for now there is no data concerning the influence of TTX on dorsal root ganglion (DRG) sensory neurons function. Thus, the present study was aimed at characterization of neurochemical coding of porcine sensory bladder-projecting cells after bladder instillation with TTX. Retrograde tracer Fast Blue (FB) was injected into the urinary bladder wall of six juvenile female pigs and three weeks later bladder instillation with TTX (12 μg per animal) was carried out in all animals. A week later, DRGs of interest were harvested from all animals and the neurochemical characterization of FB + neurons was performed using routine double-immunofluorescence labeling technique on 10-μm-thick cryostat sections. In TTX-treated animals the number of FB + cells containing galanin (GAL), nitric oxide synthase (NOS), somatostatin (SOM) and calbindin (CB) was 2.5%, 2%, 0.25% and 0.2%, respectively and that of pituitary adenylate cyclase-activating polypeptide (PACAP)-immunoreactive (IR) cells was 43%. These data when compared with previous reports, demonstrated that TTX profoundly changed the chemical coding of porcine bladder-projecting sensory neurons thus implicating that it may be used in case of hypoactivity of afferent part of reflex arc responsible for transmission of sensory information from the urinary bladder.

Section: Discussionmentioning

confidence: 99%

Tetrodotoxin induced changes in the chemical coding of dorsal root ganglion neurons supplying the porcine urinary bladder

Bossowska¹,

2012

“…Moreover, for the first time we provided some evidence that the expression of neurotransmitters in bladder afferent neurons can be down-regulated differently, depending on the spinal cord segmental level at which the parental DRG were located. In general, it is now accepted that reflex contractions of the bladder are elicited by an activation of parasympathetic preganglionic neurons located in the sacral parasympathetic nucleus found in the sacro-coccygeal spinal cord (segments S3 to Cq1 in the pig; Bossowska et al 2009), while an activation of sympathetic preganglionic neurons in the lumbar spinal cord (L3-L6 in the pig; Bossowska et al 2009) has inhibitory effects on bladder smooth muscle activity (Vaughan and Satchell 1995). Therefore, as there were two distinct "sensory centers" found along the lumbo-sacro-coccygeal DRGs, it is assumable that the functional interpretation of the alterations observed in the present study may be separately derived from the lumbar and sacro-coccygeal DRGs in which BTX-induced changes were observed.…”

Section: Discussionmentioning

confidence: 99%

Botulinum toxin type A-induced changes in the chemical coding of dorsal root ganglion neurons supplying the porcine urinary bladder

Bossowska

2012

AbsractBotulinum toxin type A (BTX) is a potent neurotoxin, which in recent years has been effectively applied in experimental treatments of many neurogenic disorders of the urinary bladder. BTX is a selective, presynaptically-acting blocking agent of acetylcholine release from nerve terminals what, in turn, leads to the cessation of somatic motor and/or parasympathetic transmission. However, application of this toxin in urological practice is still in the developmental stages and the full mechanism of its action remain elusive. Thus, the present study was aimed at investigating the neurochemical characterization of dorsal root ganglion (DRG) neurons supplying the porcine urinary bladder after BTX treatment. Retrograde tracer Fast Blue (FB) was injected into the urinary bladder wall in six juvenile female pigs and three weeks later, intramural bladder injections of BTX (100 IU per animal) were carried out in all the animals. After a week, DRG from L1 to Cq1 were harvested from the pigs and neurochemical characterization of FB + neurons was performed using double-labeling immunofluorescence technique on 10-μm-thick cryostat sections. BTX injections led to a significant decrease in the number of FB + neurons containing substance P (SP), calcitonin gene-related peptide (CGRP), calbindin (CB), somatostatin (SOM) and neuronal nitric oxide synthase (nNOS) when compared with that found in the healthy animals (19% vs. 45%, 18% vs. 36%, 0.6% vs. 3%, 0.4 vs. 4% and 0.1% vs. 6%, respectively) These data demonstrated that BTX changed the chemical coding of bladder sensory neurons, and therefore this drug should be taken into consideration when it planning experimental therapy of selected neurogenic bladder disorders.

“…Moreover, we provided, for the first time, some evidence that the expression of these substances in bladder afferent neurons can differently be up-or down-regulated in dependence on the spinal cord segmental level at which the parental DRGs were located. In general, it is now accepted that reflex contractions of the bladder are elicited by an activation of parasympathetic preganglionic neurons located in the sacral parasympathetic nucleus at the sacro-coccygeal spinal cord (segments S3 to Cq1 in the pig; see Bossowska et al 2009), while an activation of sympathetic preganglionic neurons in the lumbar spinal cord (L3-L6 in the pig; see Bossowska et al 2009) has inhibitory effects on bladder smooth muscle activity (Vaughan and Satchell 1995).…”

Section: Discussionmentioning

confidence: 99%

The influence of resiniferatoxin on the chemical coding of neurons in dorsal root ganglia supplying the urinary bladder in the female pig

Bossowska¹,

2012

Although resiniferatoxin (RTX) becomes more often used in experimental therapies of sensory system disorders, so far there is no data concerning the influence of RTX on the chemical coding of neurons in dorsal root ganglia (DRG) supplying the urinary bladder in the pig, an animal species considered as a reliable animal model for investigation dealing with human lower urinary tract disorders. Retrograde tracer Fast Blue (FB) was injected into the wall of the right half of the urinary bladder in six juvenile female pigs, and three weeks later, bladder instillation of RTX (500 nmol per animal) was carried out in all the animals. After a week, DRGs were harvested from all the pigs and the neurochemical characterization of FB + neurons was performed using routine single-immunofluorescence labeling technique on 10-μm-thick cryostat sections. RTX instillation resulted in a distinct decrease in the numbers of FB + cells containing calcitonin gene-related peptide (CGRP), nitric oxide synthase (NOS), somatostatin (SOM) and calbindin (CB) when compared with those found in the healthy animals (18% vs. 36%, 1% vs. 6%, 0.8% vs. 4% and 0.5% vs. 3%, respectively), and an increase in the number of pituitary adenylate cyclase-activating polypeptide (PACAP)-and galanin (GAL)-immunoreactive (IR) nerve cells (51% vs. 26% and 47% vs. 6.5%). The results obtained suggest that RTX could be taken into consideration when the neuroactive agents are planned to be used in experimental therapies of selected neurogenic bladder illnesses.