Axotomy of tributaries of the pelvic and pudendal nerves induces changes in the neurochemistry of mouse dorsal root ganglion neurons and the spinal cord

Abstract

Using immunohistochemical techniques, we characterized changes in the expression of several neurochemical markers in lumbar 4-sacral 2 (L4-S2) dorsal root ganglion (DRG) neuron profiles (NPs) and the spinal cord of BALB/c mice after axotomy of the L6 and S1 spinal nerves, major tributaries of the pelvic (targeting pelvic visceral organs) and pudendal (targeting perineum and genitalia) nerves. Sham animals were included. Expression of cyclic AMP-dependent transcription factor 3 (ATF3), calcitonin gene-related peptide (CGRP), transient receptor potential cation channel subfamily V, member 1 (TRPV1), tyrosine hydroxylase (TH) and vesicular glutamate transporters (VGLUT) types 1 and −2 was analysed seven days after injury. L6-S1 axotomy induced dramatic de novo expression of ATF3 in many L6-S1 DRG NPs, and parallel significant downregulations in the percentage of CGRP-, TRPV1-, TH- and VGLUT2-immunoreactive (IR) DRG NPs, as compared to their expression in uninjured DRGs (contralateral L6-S1-AXO; sham mice); VGLUT1 expression remained unaltered. Sham L6-S1 DRGs only showed a small ipsilateral increase in ATF3-IR NPs (other markers were unchanged). L6-S1-AXO induced de novo expression of ATF3 in several lumbosacral spinal cord motoneurons and parasympathetic preganglionic neurons; in sham mice the effect was limited to a few motoneurons. Finally, a moderate decrease in CGRP- and TRPV1-like-immunoreactivities was observed in the ipsilateral superficial dorsal horn neuropil. In conclusion, injury of a mixed visceral/non-visceral nerve leads to considerable neurochemical alterations in DRGs matched, to some extent, in the spinal cord. Changes in these and potentially other nociception-related molecules could contribute to pain due to injury of nerves in the abdominopelvic cavity.

Axonal Injury Induces ATF3 in Specific Populations of Sacral Preganglionic Neurons in Male Rats

“…In L6-S1 spinal cord segments, ATF3 was absent and c-Jun was rarely expressed in the IML contralateral to pelvic nerve transection (Figures 1A,B ; left panels) or on either side in the naive group (data not shown), confirming previous reports ( Peddie and Keast, 2011 ; McCarthy et al, 2016 ). However, in the ipsilateral IML (Figures 1A,B ; right panels), one or both transcription factors were expressed in the nuclei of a majority of the FG-labeled neurons (56.1 ± 2.8%, n = 6 rats; Figure 1C ).…”

Dorsal root ganglion neurons and tyrosine hydroxylase—an intriguing association with implications for sensation and pain

“…This was first observed in nodose and petrosal ganglia after axotomy of the vagus nerve or its branches as a reduction in the percentage of TH-expressing neurons [29,41,104], accompanied by a decrease in TH catalytic activity [39]. In mouse DRGs, axotomy of the sciatic [7] or pelvic nerves [65], or spinal nerve ligation [101] results in downregulated expression of TH mRNA [7] and/or protein [7,65], or of TH promoter-driven expression of enhanced green fluorescent protein [101]. In rat, sciatic nerve chronic constriction injury (CCI) leads to reduced TH mRNA content in L4-5 DRGs [30].…”

Effect of partial hysterectomy on the neurons of the paracervical ganglion (PCG) of the pig

“…A typical reaction of sympathetic neurons to axotomy is inhibition of the production of their main neurotransmitter, norepinephrine. This is related to the decrease in the expression of basic enzymes involved in its synthesis, namely TH and DβH [14,26,[30][31][32][33][34][35]. This is probably due to the lack of access to NGF, because its administration to axotomized neurons prevents the decline in TH expression [14,36].…”