Please use this identifier to cite or link to this item:
Scopus Web of Science® Altmetric
Type: Journal article
Title: Cyclic analogues of α-conotoxin Vc1.1 inhibit colonic nociceptors and provide analgesia in a mouse model of chronic abdominal pain
Other Titles: Cyclic analogues of alpha-conotoxin Vc1.1 inhibit colonic nociceptors and provide analgesia in a mouse model of chronic abdominal pain
Author: Castro, J.
Grundy, L.
Deiteren, A.
Harrington, A.
O'Donnell, T.
Maddern, J.
Moore, J.
Garcia-Caraballo, S.
Rychkov, G.
Yu, R.
Kaas, Q.
Craik, D.
Adams, D.
Brierley, S.
Citation: British Journal of Pharmacology, 2018; 175(12):2384-2398
Publisher: Wiley-Blackwell
Issue Date: 2018
ISSN: 0007-1188
Statement of
Joel Castro, Luke Grundy, Annemie Deiteren, Andrea M Harrington, Tracey O, Donnell, Jessica Maddern, Jessi Moore, Sonia Garcia-Caraballo, Grigori Y Rychkov, Rilei Yu, Quentin Kaas, David J Craik, David J Adams and Stuart M Brierley
Abstract: BACKGROUND AND PURPOSE Patients with irritable bowel syndrome suffer from chronic visceral pain (CVP) and limited analgesic therapeutic options are currently available. We have shown that α-conotoxin Vc1.1 induced activation of GABAB receptors on the peripheral endings of colonic afferents and reduced nociceptive signalling from the viscera. However, the analgesic efficacy of more stable, cyclized versions of Vc1.1 on CVP remains to be determined. EXPERIMENTAL APPROACH Using ex vivo colonic afferent preparations from mice, we determined the inhibitory actions of cyclized Vc1.1 (cVc1.1) and two cVc1.1 analogues on mouse colonic nociceptors in healthy and chronic visceral hypersensitivity (CVH) states. Using whole-cell patch clamp recordings, we also assessed the inhibitory actions of these peptides on the neuronal excitability of colonic innervating dorsal root ganglion neurons. In vivo, the analgesic efficacy of these analogues was assessed by determining the visceromotor response to colorectal distension in healthy and CVH mice. KEY RESULTS cVc1.1 and the cVc1.1 analogues, [C2H,C8F]cVc1.1 and [N9W]cVc1.1, all caused concentration-dependent inhibition of colonic nociceptors from healthy mice. Inhibition by these peptides was greater than those evoked by linear Vc1.1 and was substantially greater in colonic nociceptors from CVH mice. cVc1.1 also reduced excitability of colonic dorsal root ganglion neurons, with greater effect in CVH neurons. CVH mice treated with cVc1.1 intra-colonically displayed reduced pain responses to noxious colorectal distension compared with vehicle-treated CVH mice. CONCLUSIONS AND IMPLICATIONS Cyclic versions of Vc1.1 evoked significant anti-nociceptive actions in CVH states, suggesting that they could be novel candidates for treatment of CVP.
Keywords: Colon
Cells, Cultured
Mice, Inbred C57BL
Disease Models, Animal
Chronic Disease
Abdominal Pain
Rights: © 2017 The British Pharmacological Society
DOI: 10.1111/bph.14115
Grant ID:
Appears in Collections:Aurora harvest 8
Medicine publications

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.