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Activation of colo‐rectal high‐threshold afferent nerves by Interleukin‐2 is tetrodotoxin‐sensitive and upregulated in a mouse model of chronic visceral hypersensitivity
Author(s) -
Campaniello M. A.,
Harrington A. M.,
Martin C. M.,
Ashley Blackshaw L.,
Brierley S. M.,
Hughes P. A.
Publication year - 2016
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.12696
Subject(s) - medicine , immune system , myeloperoxidase , visceral pain , tetrodotoxin , inflammatory bowel disease , colitis , threshold of pain , inflammation , nociception , endocrinology , immunology , receptor , disease
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 Na V 1.7 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 Na V 1.7 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.