Acid and inflammatory sensitisation of naked mole-rat colonic afferent nerves.
Hockley, James Rf
Barker, Katie H
Taylor, Toni Stacey
Smith, Ewan St John
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Hockley, J. R., Barker, K. H., Taylor, T. S., Callejo, G., Husson, Z. M., Bulmer, D., & Smith, E. S. J. (2020). Acid and inflammatory sensitisation of naked mole-rat colonic afferent nerves.. Molecular pain, 16 1744806920903150. https://doi.org/10.1177/1744806920903150
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; NMR) 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 NMR interoception within the gastrointestinal tract and how this differed from the mouse (Mus Musculus). Here we show the presence of calcitonin gene regulated peptide (CGRP) expressing extrinsic nerve fibres innervating both mesenteric blood vessels and the myenteric plexi of the smooth muscle layers of the NMR colorectum. Using ex vivo colonic-nerve electrophysiological recordings we show differential sensitivity of NMR, compared to mouse, colonic afferents to acid and the prototypic inflammatory mediator bradykinin, but not direct mechanical stimuli. In NMR, but not mouse, we observed mechanical hypersensitivity to acid, whilst both species sensitised to bradykinin. Collectively, these findings suggest that NMR 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.
Gastrointestinal Tract, Afferent Pathways, Peripheral Nervous System, Animals, Mole Rats, Mice, Rats, Bradykinin, Visceral Pain
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).
Rosetrees Trust (A1296)
Arthritis Research UK (11600/21973)
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External DOI: https://doi.org/10.1177/1744806920903150
This record's URL: https://www.repository.cam.ac.uk/handle/1810/300912