Post-inflammatory colonic afferent sensitisation: different subtypes, different pathways and different time courses

Hughes, Patrick A.; Brierley, Stuart M.; Martin, Christopher M.; Brookes, Simon Jonathan; Linden, David R.; Blackshaw, L. Ashley

doi:10.1136/gut.2008.170811

Cited by 156 publications

(245 citation statements)

References 39 publications

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“…Experiments were restricted to male mice to control for the potential effects of sex steroids on pain responses (Miranda et al, 2011;Myers et al, 2011). Colitis was induced the next morning by a single intrarectal administration of 0.1 ml trinitrobenzene sulfonic acid (TNBS) (Sigma) (130 µg/ml / 30% ethanol) via a polyethylene catheter inserted 3 cm from the anus of isoflurane-anaesthetised mice as previously described (Brierley et al, 2009;Harrington et al, 2012;Hughes et al, 2009b). After 28 days mice were used for experiments.…”

Section: Chronic Visceral Hypersensitivity Model (Cvh Mice)mentioning

confidence: 99%

“…Distension of the colo-rectum is sensed by mechanosensitive extrinsic primary sensory afferent nerves, which are best characterized in the mouse (Brierley et al, 2004;Hughes et al, 2009b). Muscular / mucosal afferents respond to fine tactile stimuli and low intensity circular stretch, and in the colo-rectum are unique to the pelvic afferent pathway where they comprise approximately 25% of the total afferent population (Brierley et al, 2004;Feng et al, 2010;Hughes et al, 2009b).…”

Section: Introductionmentioning

confidence: 99%

“…Muscular / mucosal afferents respond to fine tactile stimuli and low intensity circular stretch, and in the colo-rectum are unique to the pelvic afferent pathway where they comprise approximately 25% of the total afferent population (Brierley et al, 2004;Feng et al, 2010;Hughes et al, 2009b). These afferent nerves respond linearly to increasing levels of distension and signal into the noxious range.…”

Section: Introductionmentioning

confidence: 99%

“…This colitis is transient, peaking several days after administration and then spontaneously healing such that by 28 days following administration the histology of the colon and myeloperoxidase levels do not differ from untreated animals (Hughes et al, 2009a;Hughes et al, 2009b;Krauter et al, 2007;Qin et al, 2011). However, colonic afferent nerves remain sensitized to distension long after the mucosa heals, which models aspects of the chronic visceral hypersensitivity (CVH) experienced by IBS patients (Gschossmann et al, 2004;Hughes et al, 2009a;Hughes et al, 2009b). In this model muscular / mucosal afferents are sensitized to mucosal stroking but not circular stretch, and the sensitization observed is relatively modest compared to hypersensitivity displayed by high-threshold afferents (Hughes et al, 2009b).…”

Section: Introductionmentioning

confidence: 99%

“…However, colonic afferent nerves remain sensitized to distension long after the mucosa heals, which models aspects of the chronic visceral hypersensitivity (CVH) experienced by IBS patients (Gschossmann et al, 2004;Hughes et al, 2009a;Hughes et al, 2009b). In this model muscular / mucosal afferents are sensitized to mucosal stroking but not circular stretch, and the sensitization observed is relatively modest compared to hypersensitivity displayed by high-threshold afferents (Hughes et al, 2009b). The molecular changes underlying the sensitization of colo-rectal sensory afferents following recovery from inflammation and the contribution by opioid receptors to CVH in this model remain to be determined.…”

Section: Introductionmentioning

confidence: 99%

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Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

Hughes

Moretta

Lim

et al. 2014

Brain, Behavior, and Immunity

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Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients, Brain, Behavior, and Immunity (2014), doi: http://dx.doi.org/10. 1016/j.bbi.2014.07.001 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. supernatants from HS and IBS patients were applied to colo-rectal sensory afferent endings in mice with post-inflammatory chronic visceral hypersensitivity (CVH). β-endorphin was identified predominantly in monocyte / macrophages relative to T or B cells in human PBMC and colonic lamina propria. Monocyte derived β-endorphin levels and colonic macrophage numbers were lower in IBS patients than healthy subjects. PBMC supernatants from healthy subjects had greater inhibitory effects on colo-rectal afferent mechanosensitivity than those from IBS patients. The inhibitory effects of PBMC supernatants were more prominent in CVH mice compared to healthy mice due to an increase in µ-opioid receptor expression in dorsal root ganglia neurons in CVH mice. Monocyte / macrophages are the predominant immune cell type responsible for β-endorphin secretion in humans. IBS patients have lower monocyte derived β-endorphin levels than healthy subjects, causing less inhibition of colonic afferent endings. Consequently, altered immune function contributes toward visceral hypersensitivity in IBS.

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Section: Chronic Visceral Hypersensitivity Model (Cvh Mice)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

Hughes

Moretta

Lim

et al. 2014

Brain, Behavior, and Immunity

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Sprouting of colonic afferent central terminals and increased spinal mitogen‐activated protein kinase expression in a mouse model of chronic visceral hypersensitivity

Harrington

Brierley

Isaacs

et al. 2012

J of Comparative Neurology

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Visceral pain following infection or inflammation is a major clinical problem. Although we have knowledge of how peripheral endings of colonic afferents change in disease, their central projections have been overlooked. With neuroanatomical tracing and colorectal distension (CRD), we sought to identify colonic afferent central terminals (CACTs), the dorsal horn (DH) neurons activated by colonic stimuli in the thoracolumbar (T10-L1) DH, and determine how they are altered by postinflammatory chronic colonic mechanical hypersensitivity. Retrograde tracing from the colon identified CACTs in the DH, whereas immunohistochemistry for phosphorylated MAP kinase ERK 1/2 (pERK) identified DH neurons activated by CRD (80 mmHg). In healthy mice, CACTs were located primarily in DH laminae I (LI) and V (LV) and projected down middle and lateral DH collateral pathways. CRD evoked pERK immunoreactivity in DH neurons, the majority of which were located in LI and LV, the same regions as CACTs. In postinflammatory mice, CACTs were significantly increased in T12-L1 compared with healthy mice. Although CACTs remained abundant in LI, they were more widespread and were now present in deeper laminae. After CRD, significantly more DH neurons were pERK-IR postinflammation (T12-L1), with abundant expression in LI and deeper laminae. In both healthy and postinflammatory mice, many pERK neurons were in close apposition to CACTs, suggesting that colonic afferents can stimulate specific DH neurons in response to noxious CRD. Overall, we demonstrate that CACT density and the number of responsive DH neurons in the spinal cord increase postinflammation, which may facilitate aberrant central representation of colonic nociceptive signaling following chronic peripheral hypersensitivity.

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Comparative localization of colorectal sensory afferent central projections in the mouse spinal cord dorsal horn and caudal medulla dorsal vagal complex

Wang,

Caraballo,

Rychkov

et al. 2023

J of Comparative Neurology

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The distal colon and rectum (colorectum) are innervated by spinal and vagal afferent pathways. The central circuits into which vagal and spinal afferents relay colorectal nociceptive information remain to be comparatively assessed. To address this, regional colorectal retrograde tracing and colorectal distension (CRD)‐evoked neuronal activation were used to compare the circuits within the dorsal vagal complex (DVC) and dorsal horn (thoracolumbar [TL] and lumbosacral [LS] spinal levels) into which vagal and spinal colorectal afferents project. Vagal afferent projections were observed in the nucleus tractus solitarius (NTS), area postrema (AP), and dorsal motor nucleus of the vagus (DMV), labeled from the rostral colorectum. In the NTS, projections were opposed to catecholamine and pontine parabrachial nuclei (PbN)‐projecting neurons. Spinal afferent projections were labeled from rostral through to caudal aspects of the colorectum. In the dorsal horn, the number of neurons activated by CRD was linked to pressure intensity, unlike in the DVC. In the NTS, 13% ± 0.6% of CRD‐activated neurons projected to the PbN. In the dorsal horn, at the TL spinal level, afferent input was associated with PbN‐projecting neurons in lamina I (LI), with 63% ± 3.15% of CRD‐activated neurons in LI projecting to the PbN. On the other hand, at the LS spinal level, only 18% ± 0.6% of CRD‐activated neurons in LI projected to the PbN. The collective data identify differences in the central neuroanatomy that support the disparate roles of vagal and spinal afferent signaling in the facilitation and modulation of colorectal nociceptive responses.

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Post-inflammatory colonic afferent sensitisation: different subtypes, different pathways and different time courses

Cited by 156 publications

References 39 publications

Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

Sprouting of colonic afferent central terminals and increased spinal mitogen‐activated protein kinase expression in a mouse model of chronic visceral hypersensitivity

Comparative localization of colorectal sensory afferent central projections in the mouse spinal cord dorsal horn and caudal medulla dorsal vagal complex

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