Release of endogenous opioids during a chronic IBD model suppresses the excitability of colonic DRG neurons

Valdez-Moráles, Eduardo E.; Guerrero-Alba, Raquel; Ochoa-Cortés, Fernando; Benson, Jessica R; Spreadbury, Ian; Hurlbut, David; Miranda–Morales, Marcela; Lomax, Alan E.; Vanner, Stephen

doi:10.1111/nmo.12008

Cited by 44 publications

(51 citation statements)

References 32 publications

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“…These results support the theory that neuro-immune interactions are altered in IBS patients. β-endorphin is an endogenous agonist of MOR, which we confirm is expressed and functional in colonic sensory afferents (Chatter et al, 2012;Hughes et al, 2013a;Valdez-Morales et al, 2013). The functional effects that PBMC supernatants from healthy subjects, IBS-C and IBS-D patients had in CVH mice followed a similar pattern to that we previously observed in healthy mice (Hughes et al, 2009c;Hughes et al, 2013a); whereby healthy subjects caused the most inhibition, followed by IBS-C and then IBS-D.…”

Section: Discussionsupporting

confidence: 83%

“…Indeed patients with Crohn's disease and Ulcerative Colitis experience hyposensitivity to rectal balloon pressure, which has previously been attributed to alterations in the central nervous system processing and descending inhibitory nervous pathways (Bernstein et al, 1996;Chang et al, 2000). Our studies indicate immune derived β-endorphin may also provide inhibitory influences in IBD , as has been described in mouse models of colonic inflammation, however this is yet to be investigated in humans (Valdez-Morales et al, 2013;Verma-Gandhu et al, 2007).…”

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confidence: 57%

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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: Discussionsupporting

confidence: 83%

supporting

confidence: 57%

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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“…However, the actions of endogenous opioids generated in peripheral tissues predominantly target the peripheral terminals of DRG neurons 4. This process exerts an anti-nociceptive action on pain signalling in animal studies2 3 8 12 13 and correlates with human IBD, where the visceral hyperalgesia observed in acute flare-ups14 is lost during chronic inflammation and patients often exhibit normal or even increased15 sensory thresholds.…”

Section: Introductionmentioning

confidence: 99%

Stress activates pronociceptive endogenous opioid signalling in DRG neurons during chronic colitis

Guerrero-Alba

Valdez-Moráles

Jiménez-Vargas

et al. 2016

Gut

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“…Similarly, mice chronically treated with DSS show an increase in mucosal opioid concentration, a reduction in intrinsic excitability of colonic sensory neurons, and a normal visceral sensitivity despite inflammation-induced tissue damage. 73,74 Thus, the intensity of visceral inflammatory pain seems rather dependent on the nature of the cellular infiltrate (i.e., the relative density of opioid-producing T lymphocytes) than on the inflammation-induced colonic damage.…”

Section: Endogenous Regulation Of Inflamma-tory Pain: the Janus Face mentioning

confidence: 98%

Endogenous Regulation of Inflammatory Pain by T-cell-derived Opioids

Basso¹,

Boué

Bourreille

et al. 2014

Inflammatory Bowel Diseases

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Painful sensation is a hallmark of microbe-induced inflammation. This inflammatory pain is downregulated a few days after infection by opioids locally released by effector T lymphocytes generated in response to microbe-derived antigens. This review focuses on the endogenous regulation of inflammatory pain associated with adaptive T-cell response and puts in perspective the clinical consequences of the opioid-mediated analgesic activity of colitogenic T lymphocytes in inflammatory bowel disease.

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Release of endogenous opioids during a chronic IBD model suppresses the excitability of colonic DRG neurons

Abstract: The release of endogenous opioids during chronic inflammation in mice suppresses the excitability of nociceptive DRG neurons. Targeting immune cells may provide a novel means of modulating IBD pain.

Cited by 44 publications

References 32 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

Stress activates pronociceptive endogenous opioid signalling in DRG neurons during chronic colitis

Endogenous Regulation of Inflammatory Pain by T-cell-derived Opioids

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