Activation of colo-rectal high-threshold afferent nerves by Interleukin-2 is tetrodotoxin-sensitive and upregulated in a mouse model of chronic visceral hypersensitivity

Melissa Campaniello, Andrea Harrington, C. M. Martin, L Blackshaw, Stuart Brierley, Patrick Hughes

    Research output: Contribution to journalArticle

    12 Citations (Scopus)

    Abstract

    Background: Chronic visceral pain is a defining feature of irritable bowel syndrome (IBS). IBS patients often show alterations in innate and adaptive immune function which may contribute to symptoms. Immune mediators are known to modulate the activity of viscero-sensory afferent nerves, but the focus has been on the innate immune system. Interleukin-2 (IL-2) is primarily associated with adaptive immune responses but its effects on colo-rectal afferent function in health or disease are unknown. Methods: Myeloperoxidase (MPO) activity determined the extent of inflammation in health, acute trinitrobenzene-sulfonic acid (TNBS) colitis, and in our post-TNBS colitis model of chronic visceral hypersensitivity (CVH). The functional effects of IL-2 on high-threshold colo-rectal afferents and the expression of IL-2R and NaV1.7 mRNA in colo-rectal dorsal root ganglia (DRG) neurons were compared between healthy and CVH mice. Key Results: MPO activity was increased during acute colitis, but subsided to levels comparable to health in CVH mice. IL-2 caused direct excitation of colo-rectal afferents that was blocked by tetrodotoxin. IL-2 did not affect afferent mechanosensitivity in health or CVH. However, an increased proportion of afferents responded directly to IL-2 in CVH mice compared with controls (73% vs 33%; p < 0.05), and the abundance of IL-2R and NaV1.7 mRNA was increased 3.5- and 2-fold (p < 0.001 for both) in colo-rectal DRG neurons. Conclusions & Inferences: IL-2, an immune mediator from the adaptive arm of the immune response, affects colo-rectal afferent function, indicating these effects are not restricted to innate immune mediators. Colo-rectal afferent sensitivity to IL-2 is increased long after healing from inflammation.

    Original languageEnglish
    Pages (from-to)54-63
    Number of pages10
    JournalNeurogastroenterology and Motility
    Volume28
    Issue number1
    DOIs
    Publication statusPublished - 1 Jan 2016

    Keywords

    • Colitis
    • Cytokine
    • Inflammation
    • Irritable bowel syndrome
    • Pain

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