The visceromotor responses to colorectal distension and skin pinch are inhibited by simultaneous jejunal distension

Shafton, Anthony D; Furness, John B.; Ferens, Dorota; Bogeski, G.; Koh, Shir Lin; Lean, Nicholas P; Kitchener, PD

doi:10.1016/j.pain.2006.02.018

Cited by 6 publications

(6 citation statements)

References 31 publications

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“…2 and ) ( N = 6), which were not significantly different from control ( N = 6, F = 0.03, P = 0.86, two‐way ANOVA). We also tested somatic stimuli by applying a calibrated pinch to the tail or hindlimb for 5 s, similar to that described previously (Shafton et al . 2006).…”

Section: Resultsmentioning

confidence: 99%

“…2B and C) (N = 6), which were not significantly different from control (N = 6, F = 0.03, P = 0.86, two-way ANOVA). We also tested somatic stimuli by applying a calibrated pinch to the tail or hindlimb for 5 s, similar to that described previously (Shafton et al 2006). Overall, there was no difference in the electromyographic responses from left external oblique muscle in C57BL/6 (N = 14) and ls/ls mice (Fig.…”

Section: Responses To Other Noxious Stimulimentioning

confidence: 91%

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Loss of visceral pain following colorectal distension in an endothelin‐3 deficient mouse model of Hirschsprung's disease

Zagorodnyuk

Kyloh

Nicholas

et al. 2011

The Journal of Physiology

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Non-technical summary The endothelin-3 (ET-3) gene is essential for the development of the enteric nervous system in the gastrointestinal tract of mammals, including humans and mice. Loss of the ET-3 gene leads to the formation of an aganglionic colorectum and impaired bowel function. Endogenous endothelin peptides and their receptors also play a major role in nociception in a variety of organs and species, including humans. However, whether nociception is altered in the aganglionic region of the colorectum is unknown. We show that in ET-3 deficient mice, there is a loss of nociception from the aganglionic rectum, but not other visceral organs. This loss of nociception is due to a reduction in spinal afferent innervation and a selective deficiency in specific classes of rectal afferent nerve fibres, which are necessary for detection of noxious stimuli from this region.Abstract Endothelin peptides and their endogenous receptors play a major role in nociception in a variety of different organs. They also play an essential role in the development of the enteric nervous system. Mice with deletions of the endothelin-3 gene (lethal spotted mice, ls/ls) develop congenital aganglionosis. However, little is known about how nociception might be affected in the aganglionic rectum of mice deficient in endothelin-3. In this study we investigated changes in spinal afferent innervation and visceral pain transmission from the aganglionic rectum in ls/ls mice. Electromyogram recordings from anaesthetized ls/ls mice revealed a deficit in visceromotor responses arising from the aganglionic colorectum in response to noxious colorectal distension. Loss of visceromotor responses (VMRs) in ls/ls mice was selective, as no reduction in VMRs was detected after stimulation of the bladder or somatic organs. Calcitonin gene related peptide (CGRP) immunoreactivity, retrograde neuronal tracing and extracellular afferent recordings from the aganglionic rectum revealed decreased colorectal spinal innervation, combined with a reduction in mechanosensitivity of rectal afferents. The sensory defect in ls/ls mice is primarily associated with changes in low threshold wide dynamic range rectal afferents. In conclusion, disruption of endothelin 3 gene expression not only affects development and function of the enteric nervous system, but also specific classes of spinal rectal mechanoreceptors, which are required for visceral nociception from the colorectum.

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Section: Resultsmentioning

confidence: 99%

Section: Responses To Other Noxious Stimulimentioning

confidence: 91%

Loss of visceral pain following colorectal distension in an endothelin‐3 deficient mouse model of Hirschsprung's disease

Zagorodnyuk

Kyloh

Nicholas

et al. 2011

The Journal of Physiology

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“…In other experiments, anaesthesia was maintained with intra‐arterial infusion of a mixture of α ‐chloralose (6–12 mg kg h −1 ) and pentobarbitone (4–7 mg kg h −1 ). EMG was recorded from the abdominal muscle and EMG discharge was used as a measure of cutaneous (skin pinch; SP) or visceral (CRD) pain, as previously described 26 . In summary, to detect the EMG a pair of fine, gold‐plated, tungsten wires, 125 μ m in diameter and separated by 2 mm, was inserted in the external oblique muscle of the abdominal wall, over the position of the right lobe of the liver.…”

Section: Methodsmentioning

confidence: 99%

“…EMG was recorded from the abdominal muscle and EMG discharge was used as a measure of cutaneous (skin pinch; SP) or visceral (CRD) pain, as previously described. 26 In summary, to detect the EMG a pair of fine, gold-plated, tungsten wires, 125 lm in diameter and separated by 2 mm, was inserted in the external oblique muscle of the abdominal wall, over the position of the right lobe of the liver. Blood pressure was measured from the femoral artery.…”

Section: Methodsmentioning

confidence: 99%

Effects of NMDA receptor antagonists on visceromotor reflexes and on intestinal motility, in vivo

Shafton¹,

Bogeski²,

Kitchener³

et al. 2007

Neurogastroenterology Motil

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Antagonists of NMDA receptors can inhibit both the transmission of pain signals from the intestine and enteric reflexes. However, it is unknown whether doses of the NMDA antagonist, ketamine, that are used in anaesthetic mixtures suppress motility reflexes and visceromotor responses (VMRs). In fact, whether intestinal motility is affected by NMDA receptor blockers in vivo has been little investigated. We studied the effects of ketamine and memantine, administered intravenously or intrathecally. Rats were maintained under alpha-chloralose plus xylazine or pentobarbitone anaesthesia; VMR and jejunal motility were measured. Under alpha-chloralose/xylazine anaesthesia, i.v. ketamine inhibited VMRs at 6 mg kg h(-1), but not at 3 mg kg h(-1). It did not inhibit propulsive reflexes in the jejunum at 10 mg kg h(-1), but reduced them by 30% at 20 mg kg h(-1). Under alpha-chloralose/pentobarbitone anaesthesia, i.v. ketamine reduced propulsive reflexes at 40 mg kg h(-1) and VMR at 10 mg kg h(-1). Memantine inhibited VMRs at 20 mg kg h(-1) and propulsion at 2 mg kg h(-1). Ketamine and memantine, intrathecally, prevented VMRs, but not jejunal propulsion. We conclude that peripherally administered ketamine reduces both VMR and motility reflexes, but not at doses used in anaesthetic mixes (1.8-2.4 mg kg h(-1)). Effects on motility reflexes are likely to be due to non-NMDA receptor actions, possibly on nicotinic receptors.

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“…Increased sensitivity to colorectal distention has been observed in IBS patients as a common manifestation of the disease. In fact, colorectal distention is considered as a kind of mechanical stimulation or noxious visceral challenge used to induce visceral hyperalgesia and the associated visceral pain [ 58 ]. This experimental procedure is widely accepted and highly reproducible for the assessment of visceral hypersensitivity in both clinical and preclinical trials.…”

Section: Preclinical Experimental Models Of Ibsmentioning

confidence: 99%

Pathogenesis, Experimental Models and Contemporary Pharmacotherapy of Irritable Bowel Syndrome: Story About the Brain-Gut Axis

Tsang¹,

Auyeung²,

Bian³

et al. 2016

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BackgroundAlthough the precise pathophysiology of irritable bowel syndrome (IBS) remains unknown, it is generally considered to be a disorder of the brain-gut axis, representing the disruption of communication between the brain and the digestive system. The present review describes advances in understanding the pathophysiology and experimental approaches in studying IBS, as well as providing an update of the therapies targeting brain-gut axis in the treatment of the disease.MethodsCausal factors of IBS are reviewed. Following this, the preclinical experimental models of IBS will be introduced. Besides, both current and future therapeutic approaches of IBS will be discussed.ResultsWhen signal of the brain-gut axis becomes misinterpreted, it may lead to dysregulation of both central and enteric nervous systems, altered intestinal motility, increased visceral sensitivity and consequently contributing to the development of IBS. Interference of the brain-gut axis can be modulated by various psychological and environmental factors. Although there is no existing animal experiment that can represent this complex multifactorial disease, these in vivo models are clinically relevant readouts of gastrointestinal functions being essential to the identification of effective treatments of IBS symptoms as well as their molecular targets. Understanding the brain-gut axis is essential in developing the effective therapy for IBS. Therapies include improvement of GI motor functions, relief of visceral hypersensitivity and pain, attenuation of autonomic dysfunctions and suppression of mucosal immune activation.ConclusionTarget-oriented therapies that provide symptomatic, psychological and physiological benefits could surely help to improve the quality of life of IBS patients.

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The visceromotor responses to colorectal distension and skin pinch are inhibited by simultaneous jejunal distension

Cited by 6 publications

References 31 publications

Loss of visceral pain following colorectal distension in an endothelin‐3 deficient mouse model of Hirschsprung's disease

Loss of visceral pain following colorectal distension in an endothelin‐3 deficient mouse model of Hirschsprung's disease

Effects of NMDA receptor antagonists on visceromotor reflexes and on intestinal motility, in vivo

Pathogenesis, Experimental Models and Contemporary Pharmacotherapy of Irritable Bowel Syndrome: Story About the Brain-Gut Axis

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