Journal article
A spider-venom peptide with multitarget activity on sodium and calcium channels alleviates chronic visceral pain in a model of irritable bowel syndrome
Pain, Vol.162(2), pp.569-581
2021
PMID: 32826759
Abstract
Chronic pain is a serious debilitating condition that affects ;20% of the world's population. Currently available drugs fail to produce effective pain relief in many patients and have dose-limiting side effects. Several voltage-gated sodium (Na V) and calcium (Ca V) channels are implicated in the etiology of chronic pain, particularly Na V 1.1, Na V 1.3, Na V 1.7–Na V 1.9, Ca V 2.2, and Ca V 3.2. Numerous Na V and Ca V modulators have been described, but with few exceptions, they display poor potency and/or selectivity for pain-related channel subtypes. Here, we report the discovery and characterization of 2 novel tarantula-venom peptides (Tap1a and Tap2a) isolated from Theraphosa apophysis venom that modulate the activity of both Na V and Ca V 3 channels. Tap1a and Tap2a inhibited on-target Na V and Ca V 3 channels at nanomolar to micromolar concentrations and displayed moderate off-target selectivity for Na V 1.6 and weak affinity for Na V 1.4 and Na V 1.5. The most potent inhibitor, Tap1a, nearly ablated neuronal mechanosensitivity in afferent fibers innervating the colon and the bladder, with in vivo intracolonic administration reversing colonic mechanical hypersensitivity in a mouse model of irritable bowel syndrome. These findings suggest that targeting a specific combination of Na V and Ca V 3 subtypes provides a novel route for treatment of chronic visceral pain.
Details
- Title
- A spider-venom peptide with multitarget activity on sodium and calcium channels alleviates chronic visceral pain in a model of irritable bowel syndrome
- Authors
- Fernanda C Cardoso (Author) - The University of QueenslandJoel Castro (Author) - Flinders UniversityLuke Grundy (Author) - Flinders UniversityGudrun Schober (Author) - Flinders UniversitySonia Garcia-Caraballo (Author) - Flinders UniversityTianjiao Zhao (Author) - The University of QueenslandVolker Herzig (Author) - University of the Sunshine Coast, Queensland, School of Science, Technology and EngineeringGlenn F King (Author) - The University of QueenslandStuart M Brierley (Author) - Flinders UniversityRichard J Lewis (Author) - The University of Queensland
- Publication details
- Pain, Vol.162(2), pp.569-581
- Publisher
- Lippincott Williams & Wilkins
- Date published
- 2021
- DOI
- 10.1097/j.pain.0000000000002041
- ISSN
- 1872-6623
- PMID
- 32826759
- Organisation Unit
- University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99482295902621
- Output Type
- Journal article
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- Domestic collaboration
- Web Of Science research areas
- Anesthesiology
- Clinical Neurology
- Neurosciences
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