Colokinetic effect of noradrenaline in the spinal defecation center: implication for motility disorders

Abstract

Chronic abdominal pain in irritable bowel syndrome (IBS) usually appears in combination with disturbed bowel habits, but the etiological relationship between these symptoms remains unclear. Noradrenaline is a major neurotransmitter controlling pain sensation in the spinal cord. To test the hypothesis that the descending noradrenergic pathway from the brain stem moderates gut motility, we examined effects of intrathecal application of noradrenaline to the spinal defecation center on colorectal motility. Colorectal intraluminal pressure and expelled volume were recorded in vivo in anesthetized rats. Intrathecal application of noradrenaline into the L6-S1 spinal cord, where the lumbosacral defecation center is located, caused propulsive contractions of the colorectum. Inactivation of spinal neurons by tetrodotoxin blocked the effect of noradrenaline. Pharmacological experiments showed that the effect of noradrenaline is mediated primarily by alpha-1 adrenoceptors. The enhancement of colorectal motility by intrathecal noradrenaline was abolished by severing of the pelvic nerves. Our results demonstrate that noradrenaline acting on sacral parasympathetic preganglionic neurons through alpha-1 adrenoceptors causes propulsive motility of the colorectum in rats. Considering that visceral pain activates the descending inhibitory pathways including noradrenergic neurons, our results provide a rational explanation of the concurrent appearance of chronic abdominal pain and colonic motility disorders in IBS patients.

Exogenous serotonin regulates colorectal motility via the 5‐HT2 and 5‐HT3 receptors in the spinal cord of rats

“…We previously demonstrated that intrathecal administration of NA and DA caused propulsive contractions of the colorectum via activation of the lumbosacral defecation center. These findings allow us to propose a novel hypothesis that descending pain inhibitory pathways modulate not only pain but also the defecation reflex in the lumbosacral spinal cord . This study showing that 5‐HT injected into the lumbosacral spinal cord activates colorectal motility confirms our hypothesis, because 5‐HT is known to be a neurotransmitter of the descending pain inhibitory pathways, the origin of which is the rostral ventromedial medulla including the raphe magnus .…”

“…In previous studies, we showed that NA and DA have colokinetic effects in the lumbosacral defecation center. 14,15 Since 5-HT activates sacral parasympathetic preganglionic neurons, in a similar way to the actions of NA and DA, it was of interest to examine the interaction be- Figure 5D). It should be noted that the mixture of NA and DA did not enhance colorectal motility in the absence of preceding 5-HT (data not shown).…”

“…Parasympathetic outflows from the lumbosacral defecation center directly project to the enteric nervous system (ENS) of the colorectum, and the pontine defecation center indirectly controls colorectal motility through interacting with the lumbosacral defecation center . In previous studies, we have shown that intrathecal administration of noradrenaline (NA) or dopamine (DA) caused enhancement of colorectal motility . In the spinal cord, these monoamine neurotransmitters are supplied from descending neurons from the brain stem to control pain processing .…”

“…12,13 In previous studies, we have shown that intrathecal administration of noradrenaline (NA) or dopamine (DA) caused enhancement of colorectal motility. 14,15 In the spinal cord, these monoamine neurotransmitters are supplied from descending neurons from the brain stem to control pain processing. 16 Based on the fact that colorectal motility disorder is concurrent with hyperalgesia in IBS, 17 we hypothesized that descending pain inhibitory pathways influence the defecation center in the lumbosacral spinal cord.…”

<b>Noradrenergic effects in rat sacral autonomic nucleus using in vitro slice patch-clamp r</b><b>ecordings </b>

“…The reverse potential of K + in this experiment was around −90 mV, which the pontine micturition center, and administration of NA initiates the micturition reflex in some bladder conditions (28). Also, α1 receptor-mediated facilitations of colonic mortalities in the spinal cord were reported in defecation systems (22,23). Our findings showing excitation through α1 receptor of labeled-PGNs and enhancement of sEPSC may explain the mechanisms of those reports.…”