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

Abstract

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.

Somatostatin-like immunoreactive primary sensory neurons supplying the porcine adrenal glands in physiological conditions and after adrenalectomy

“…An increase in the number of SOM-LI neurons of dorsal root ganglia during pathological processes, observed both in previous studies (4,5,15) and in the present study, may arise from the augmentation of SOM synthesis as an adaptive process within the nervous system, but it could also indicate an inhibition of the SOM release from nerve endings. The augmentation of SOM synthesis, which on the grounds of well-known anti-nociceptive actions of this peptide (12, 13) is more probable, can be connected with altered activity of the sensory neurons under noxious factors.…”

“…Namely, post-axotomical augmentation of SOM-like immunoreactivity has been described in the porcine autonomic nervous system (15). Moreover, scanty information concerning SOMpositive sensory neurons in porcine DRG revealed that the percentage of such cells supplying the urinary bladder increases under the influence of selected toxins (4,5).…”

The Influence of Tetrodotoxin (TTX) on the Distribution and Chemical Coding of Caudal Mesenteric Ganglion (CaMG) Neurons Supplying the Porcine Urinary Bladder

“…Immunohistochemistry involved double stainings which were performed according to an earlier described method [47]. They were applied to cryostat sections from both the ipsi- and contralateral CaMG.…”

Botulinum toxin A, brain and pain

“…Authors proposed that the binding activity of BoNT/A heavy chain alone is sufficient to promote neuritogenesis (Coffield and Yan, 2009). Bossowska and Majewski (2012) reported that BoNT/A injection into bladder reduces the number of sensory neurons containing substance P, CGRP, calbindin, somatostatin, and neuronal nitric oxide synthase in ganglia innervating the bladder. The mechanism of these changes might be connected with altered gene expression.…”