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

Andrea Harrington, Stuart Brierley, Nicole Isaacs, Patrick Hughes, Joel Castro, L. Ashley Blackshaw

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    38 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)2241-2255
    Number of pages15
    JournalJournal of Comparative Neurology
    Volume520
    Issue number10
    DOIs
    Publication statusPublished - 1 Jul 2012

    Keywords

    • Colonic afferent fibers
    • Colonic inflammation
    • Immunohistochemistry
    • Mouse and spinal cord
    • Neuroanatomical tracing

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