Characterizing the mechanical properties of ectopic axonal receptive fields in inflamed nerves and following axonal transport disruption

Goodwin, George, Bove, Geoffrey M, Dayment, Bryony and Dilley, Andrew (2019) Characterizing the mechanical properties of ectopic axonal receptive fields in inflamed nerves and following axonal transport disruption. Neuroscience, 429. pp. 10-22. ISSN 0306-4522

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Abstract

Radiating pain is a significant feature of chronic musculoskeletal pain conditions such as radiculopathies, repetitive motion disorders and whiplash associated disorders. It is reported to be caused by the development of mechanically-sensitive ectopic receptive fields along intact nociceptor axons at sites of peripheral neuroinflammation (neuritis). Since inflammation disrupts axonal transport, we have hypothesised that anterogradely-transported mechanically sensitive ion channels accumulate at the site of disruption, which leads to axonal mechanical sensitivity (AMS). In this study, we have characterised the mechanical properties of the ectopic axonal receptive fields and have examined the contribution of mechanically sensitive ion channels to the development of AMS following neuritis and vinblastine-induced axonal transport disruption. In both models, there was a positive force-discharge relationship and mechanical thresholds were low (~9 mN/mm2). All responses were attenuated by ruthenium red and FM1-43, which block mechanically sensitive ion channels. In both models, the transport of TRPV1 and TRPA1 was disrupted, and intraneural injection of agonists of these channels caused responses in neurons with AMS following neuritis but not vinblastine treatment. In summary, these data support a role for mechanically sensitive ion channels in the development of AMS.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Neuroscience
Subjects: R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry
Depositing User: Andrew Dilley
Date Deposited: 02 Dec 2019 10:53
Last Modified: 24 Jan 2020 16:00
URI: http://sro.sussex.ac.uk/id/eprint/88358

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