Resiniferatoxin and Tetrodotoxin Induced NPY and TH Immunoreactivity Changes Within the Paracervical Ganglion Neurons Supplying the Urinary Bladder

Piotr J Burliński,Sławomir Gonkowski,Jarosław Całka,Anna M Burlińska

doi:10.1007/s12031-012-9889-z

Abstract

Both resiniferatoxin (RTX) and tetrodotoxin (TTX) have been reported to be effective in several urinary bladder dysfunction clinical trials. The aim of this study was to establish the effect of intravesical administration of RTX and TTX on neuropeptides Y (NPY) and tyrosine hydroxylase (TH) relationship in the paracervical ganglion (PCG) neurons supplying the urinary bladder in the pig. TH is an enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to dihydroxyphenylalanine (DOPA) and is used as a marker of catecholaminergic neurons. NPY augments the vasoconstrictor effects of noradrenergic neurons, and is involved in pathophysiological processes as a neuromodulator. To identify the PCG neurons supplying urinary bladder Fast Blue (FB) was injected into the bladder wall prior to intravesical RTX or TTX administration. Consequent application of immunocytochemical methods revealed that in control group 64.08 % of FB-positive PCG neurons contain NPY and 4.25 % TH. Intravesical infusion of RTX resulted upregulation of the NPY-IR neurons to 82.97 % and TH-IR to 43.78 %. Also administration of TTX induced further increase number of TH-IR neurons to 77.49 % but induced decrease number of NPY-IR neurons to 57.45 %. Both neurotoxins affect chemical coding of the PCG neural somata supplying urinary bladder, but the effects of their action are different. This results shed light on possible involvement of RTX and TTX on curing tissue, and potentially could help us to broaden our neurourological armamentarium.

Highlights

The treatment of micturition disorders, such as overactivity/ hyperactivity of the bladder, remains a problem for neurourologists
Triple-labeled Fast Blue (FB)+/ neuropeptides Y (NPY)+/tyrosine hydroxylase (TH)+ somata accounted for 1.91 % of the FB-positive neurons
The present investigation reports on the effect of an intravesical administration of RTX and TTX on NPY and TH expression in paracervical ganglion neurons supplying the urinary bladder in the pig

Summary

Introduction

The treatment of micturition disorders, such as overactivity/ hyperactivity of the bladder, remains a problem for neurourologists. In the last few years, for example, O-conotoxin GIVA, botulinum toxin, guanethidine, resiniferatoxin (RTX) and tetrodotoxin (TTX) were intensively studied (Radziszewski and Borkowski 2001; Apostolidis et al 2006; Bossowska et al 2008; Bossowska et al 2009; Lepiarczyk et al 2010; Lew et al 2010a; Lew et al 2010b; Burliński et al 2011; Burliński et al 2012). The evaluation of neurotoxin influence on the chemical coding of the neurons supplying the urinary bladder may increase our knowledge about the consequences of their action on treated tissue and organisms. This may help to broaden neuro-urological armamentarium by enabling a better choice of treatment for specific micturition disorders.

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