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Acid and inflammatory sensitisation of naked mole-rat colonic afferent nerves.

Accepted version
Peer-reviewed

Type

Article

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Authors

Hockley, James Rf 
Barker, Katie H 
Taylor, Toni S 
Callejo, Gerard 
Husson, Zoe M 

Abstract

Acid sensing in the gastrointestinal tract is required for gut homeostasis and the detection of tissue acidosis caused by ischaemia, inflammation and infection. In the colorectum, activation of colonic afferents by low pH contributes to visceral hypersensitivity and abdominal pain in human disease including during inflammatory bowel disease. The naked mole-rat (Heterocephalus glaber) shows no pain-related behaviour to subcutaneous acid injection and cutaneous afferents are insensitive to acid, an adaptation thought to be a consequence of the subterranean, likely hypercapnic, environment in which it lives. As such we sought to investigate naked mole-rat interoception within the gastrointestinal tract and how this differed from the mouse (Mus Musculus). Here, we show the presence of calcitonin gene-related peptide expressing extrinsic nerve fibres innervating both mesenteric blood vessels and the myenteric plexi of the smooth muscle layers of the naked mole-rat colorectum. Using ex vivo colonic-nerve electrophysiological recordings, we show differential sensitivity of naked mole-rat, compared to mouse, colonic afferents to acid and the prototypic inflammatory mediator bradykinin, but not direct mechanical stimuli. In naked mole-rat, but not mouse, we observed mechanical hypersensitivity to acid, whilst both species sensitised to bradykinin. Collectively, these findings suggest that naked mole-rat colonic afferents are capable of detecting acidic stimuli; however, their intracellular coupling to downstream molecular effectors of neuronal excitability and mechanotransduction likely differs between species.

Description

Keywords

Acid, bradykinin, mechanosensation, sensitisation, visceral pain, Afferent Pathways, Animals, Bradykinin, Gastrointestinal Tract, Mice, Mole Rats, Peripheral Nervous System, Rats, Visceral Pain

Journal Title

Mol Pain

Conference Name

Journal ISSN

1744-8069
1744-8069

Volume Title

16

Publisher

SAGE Publications
Sponsorship
Rosetrees Trust (A1296)
Biotechnology and Biological Sciences Research Council (BB/R006210/1)
Arthritis Research UK (11600/21973)
The authors declare no competing financial interests. This work was supported by Rosetrees Postdoctoral Grant (A1296; JRFH and EStJS), BBSRC grant (BB/R006210/1; JRFH and EStJS), Versus Arthritis Pain Challenge Grant (RG21973; GC and EStJS), AstraZeneca PhD studentshipt (KHB), EMBO Long-Term Fellowship (ALTF1565-2015; ZH) and University of Cambridge Vice Chancellor’s Award (TST).