Spinal neurons activated in response to pudendal or pelvic nerve stimulation in female rats

Abstract

The overlapping distribution of spinal neurons activated with either pudendal sensory nerve or pelvic nerve stimulation was examined in the female rat using c-fos immunohistochemistry. Pudendal sensory nerve stimulation resulted in a significant increase in fos-positive cells in the ipsilateral dorsal horn and bilaterally in the medial, lateral and intermediate gray of L5-S1. Pelvic nerve stimulation resulted in significant increases of c-fos immunoreactive nuclei in the ipsilateral dorsal horn, lateral and intermediate gray and bilaterally in the medial gray of L5-S1. Co-distribution of fos immunoreactive nuclei with the vesicular glutamate transporters (VGlut2 and VGlut3) and neurokinin I receptors were found in distinct regions of the dorsal horn, medial and lateral gray. Specific areas in the medial dorsal horn, dorsal gray commissure, laminae VI and X and dorsal lateral gray were activated after stimulation of the pudendal sensory and pelvic nerves, suggesting these areas contain spinal neurons that receive both somatomotor and visceral inputs and are part of the intraspinal circuit that regulates sexual and voiding function.

Novel spinal pathways identified by neuronal c-Fos expression after urethrogenital reflex activation in female guinea pigs

“…The sensory inputs responsible for the enhanced c-Fos expression most likely reach the spinal cord via the pudendal nerve which provides most of the sensory innervation to the urethra (Vilimas et al, 2011;Wiedey et al, 2008). The increased cFos expression at both sacral and lumbar levels was consistent with our previous electrophysiological observations, in which electrical stimulation of pudendal nerves activates not only a local pudendal nerve-sacral spinal cord-pelvic nerve pathway but also a more cranial pudendal nerve-lumbar spinal cord-hypogastric nerve pathway via ascending inter-segmental connections between sacral and lumbar spinal segments ( Figure 9A) .…”

“…Two aspects of our data predict that these spinal pathways are related to pain perception: (1) c-Fos expression in superficial dorsal horn neurons is up-regulated almost exclusively by nociceptive inputs (Coggeshall, 2005); and (2) many of these c-Fos expressing neurons were found to be surrounded by CGRP-immunoreactive fibres, which are known to be primarily nocicieptive (Morris et al, 2005b). The complexity of the pathways is further demonstrated by the presence of three sensory-autonomic pathways regulating pelvic organs activity: (1) pudendal nerve inputs to sacral spinal cord with outputs via the pelvic nerve; (2) pudendal nerve inputs to sacral spinal cord with ascending pathways to lumbar outputs via lumbar splanchnic and hypogastric nerves; and (3) hypogastric nerve inputs to lumbar spinal cord with outputs via lumbar splanchnic and hypogastric nerves (Dail et al, 1985;Jobling et al, 2003;Morris and Gibbins,1987;Morris et al, 2005a;Papka and Traurig, 1993;Sato et al, 1996;Traurig and Papka, 1993;Wiedey et al, 2008;Yuan et al, 2011). In addition, there is a significant degree of intra-spinal modulation within both ascending and descending pathways .…”

“…The responses to the UGR activation in female animals resemble those seen during sexual activity, including significant increases in pelvic blood flow and rhythmic contractions of the vagina and uterus (Bohlen et al, 1982a(Bohlen et al, , 1982bSipski, 2001). Afferent input arises from the pudendal nerves and the visceral responses themselves are produced by activation of autonomic pathways comprising 5 spinal preganglionic neurons, the hypogastric and pelvic nerves, with final motor neurons in the paracervical (anterior pelvic) ganglia (Morris and Gibbins, 1987;Keast, 1999;Jobling et al, 2003;Morris et al, 2005a;Wiedey, 2008). In guinea pigs, pudendal nerves project from sacral spinal cord mainly at S2 segment, hypogastric from rostral lumbar (eg.…”

“…Expression levels of an immediate-early proto-oncogene protein, c-Fos, in spinal cord neurons are increased by activation of nociceptive sensory neurons, providing a valuable tool to identify neurons within spinal nociceptive pathways (Morgan et al, 1987;Marson et al, 2003;Marson and Gravitt, 2004;Coggeshall, 2005;Wiedey et al, 2008;Gao and Ji, 2009;Wang et al, 2010). Indeed, immunohistochemical mapping of c-Fos expression has allowed the identification of several populations of spinal neurons activated by stimulation of pelvic and pudendal nerves as well as the UGR (Marson et al, 2003).…”

Altered spinal cord activity during sexual stimulation in women with SCI: a pilot fMRI study

“…Laboratory studies in women with specific levels and degrees of SCIs have been used to map the neurological control of sexual responses, and the peripheral and genital responses of women with SCIs have been assessed in response to sexual arousal and orgasm. However, although animal studies have documented the location of spinal neurons activated in response to pelvic and pudendal nerve stimulation 8 and the impact of somatosensory stimulation on both vaginal blood flow and the urethrogenital reflex, 9 we have yet to observe the actual neurological events occurring in the spinal cords of women with SCIs. Therefore, building on recent studies using functional magnetic resonance imaging (fMRI) to study spinal cord responses to sexual stimulation in able-bodied men 10 and women, 11 this case series is aimed at determining the feasibility of performing spinal cord fMRI on women with SCIs and whether this approach can be utilized in future studies to assess sexual responses among SCI patients.…”