Conantokin G-induced changes in the chemical coding of dorsal root ganglion neurons supplying the porcine urinary bladder

Abstract

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.

Co-expression of PACAP with VIP, SP and CGRP in the Porcine Nodose Ganglion Sensory Neurons

“…() who reported on the presence of the PACAP‐IR perikarya in the jugular–nodose ganglion in rat. Although expression of PACAP in the distal ganglion of the vagus has not been extensively studied through different species, PACAP‐IR neurons have been identified in spinal ganglia of the pig (Bossowska and Majewski, ), as well as spinal and trigeminal ganglia of the rat (Moller et al., ; Zhang et al., ). Detection of PACAP in sensory ganglia directly implicates this peptide in nociceptive transmission (Nemeth et al., ; Helyes et al., ; Gonkowski and Całka, ).…”