Differential Processing of Noxious Colonic Input by Thoracolumbar and Lumbosacral Dorsal Horn Neurons in the Rat

Abstract

Wang, Gexin, Bin Tang, and Richard J. Traub. Differential processing of noxious colonic input by thoracolumbar and lumbosacral dorsal horn neurons in the rat. J Neurophysiol 94: 3788 -3794, 2005. First published August 10, 2005; doi:10.1152/jn.00230.2005. Previous studies suggest the lumbosacral (LS) spinal cord processes acute colorectal stimuli whereas the thoracolumbar (TL) and LS spinal segments process inflammatory stimuli. In this study, the effects of colorectal distention (CRD) on TL and LS dorsal horn neuronal activity were recorded in Nembutal-anesthetized male rats both with and without colonic inflammation. Both single cells (before and after inflammation) and populations (multiple cells from noninflamed or inflamed rats) were studied. CRD-responsive neurons had excitatory Abrupt (ON-OFF with stimulus) or Sustained (prolonged after discharge) responses or were Inhibited by CRD. In noninflamed rats, a significantly greater percentage of LS neurons (63% Abrupt, 27% Sustained) were excited by CRD than TL neurons (61% Abrupt, 3% Sustained). The remaining cells were Inhibited (10% LS, 36% TL). LS Abrupt neurons had lower thresholds and greater response magnitudes to CRD compared with TL Abrupt neurons. After colonic inflammation, TL neurons became more excitable: the percentage of Inhibited neurons decreased, the response magnitude of Abrupt neurons increased, and the threshold decreased. In contrast, in single-cell recordings, the response of LS Sustained neurons increased, whereas LS Abrupt neurons decreased. These data suggest that in noninflamed rats, the net response to CRD of TL visceroceptive spinal sensory neurons is less than that of LS neurons. Colonic inflammation increases the net response of TL neurons and differentially modulates the response of LS neurons. These differences may contribute to the functional dichotomy between the TL and LS spinal segments in processing acute and inflammatory colorectal pain. I N T R O D U C T I O NA unique feature of the viscera is dual innervation by sensory afferent fibers projecting in the same nerves as sympathetic (splanchnic, hypogastric) and parasympathetic (vagal, pelvic) efferents. In the rat, the descending colon and rectum are innervated by primary afferent fibers projecting in the pelvic nerve to the L6 -S2 spinal cord segments and hypogastric/lumbar colonic nerves projecting to the T13-L2 spinal cord (Mayer and Gebhart 1994; Mayer and Raybould 1990; Nadelhaft and Booth 1984; Ness and Gebhart 1988; Traub et al. 1999). However, the physiological role of this dual innervation in visceral nociceptive processing is unclear. Previous studies suggest that the lumbosacral (LS) and thoracolumbar (TL) spinal cord segments process acute and inflammatory pain from the colon and rectum differently. In humans, referred pain evoked by colorectal distention (CRD) in normal volunteers is perceived in the sacral dermatomes, whereas patients with irritable bowel syndrome or Crohn's disease report referred pain expanding into the TL dermatomes (Bernstein et al. 199...

Differential roles of stretch-sensitive pelvic nerve afferents innervating mouse distal colon and rectum

“…These findings are supported by evidence in the mouse that the PN pathway contains a significantly larger proportion of stretch-sensitive afferents (44% compared with 10% in the LSN) (5), which encodes colorectal distension to drive the visceromotor response, a reliable and widely accepted metric of evoked visceral nociception and hypersensitivity (11,20,25,26). It has been suggested that LSN input assumes a role in colorectal nociception in the presence of inflammation (39).…”

Pelvic Nerve Input Mediates Descending Modulation of Homovisceral Processing in the Thoracolumbar Spinal Cord of the Rat

“…There is an increase in the discharge of TL dorsal horn neurons, an increase in CRD-induced Fos expression and the TL dorsal horn contributes to behavioral responses to CRD 7,9,10 . These data are similar to the present observations following acute neurectomy or spinal cold block/transection although the experimental manipulations are in opposite directions (increasing or decreasing colonic input to the LS dorsal horn).…”

Acute Colitis Enhances Responsiveness of Lumbosacral Spinal Neurons to Colorectal Distension in Rats

“…It has been shown that colorectal inflammation with turpentine (1 h-48 h) in spinalized rats increases spontaneous activity and CRD-evoked responses in sustained neurons, whereas abrupt neurons have decreased spontaneous activity and CRD-evoked responses [10]. Similar observations in lumbosacral spinal neurons are observed in rats with mustard oil applied in the colon for 30 min to 4 h [12]. It is believed that selective alterations in central inhibitory mechanisms contribute to inflammation-induced increases in reflex responses to CRD.…”

“…For example, in intact or hormonally modulated female rats, colonic inflammation facilitates the response of abrupt neurons, but does not affect sustained neurons [13]. Cold block of the spinal cord causes abrupt neurons to develop an afterdischarge similar to that of sustained neurons [12]. Furthermore, in primary central sensitization induced by corticosterone implanted in the amygdala but in the absence of colonic inflammation, increased responsiveness to CRD is observed in both the SL-E and the LL-E groups of lumbosacral neurons [24].…”

“…However, previous studies that used electrophysiological techniques to examine spinal neuronal responses to noxious colonic stimulation administered short-term (minutes to hours) colonic irritants, which is more comparable to an instant noxious stimulus rather than an inflammatory course similar to a clinical situation. For example, spinal neuronal hyperexcitability or hypersensitivity has been determined in rats after pretreatment with colonic acetic acid for 45 min [7,8]; with colonic turpentine for 2-48 h [9,10], and with colonic mustard oil for 30 min to a few hours [11][12][13]. In these cases, colorectal irritation may not be long enough to allow the colon and pain pathways to fully develop symptomatic and adaptive responses to pathological alterations that are observed clinically.…”