Dataset Information

Characterizing the Mechanical Properties of Ectopic Axonal Receptive Fields in Inflamed Nerves and Following Axonal Transport Disruption.

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 in the rat 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.

SUBMITTER: Goodwin G

PROVIDER: S-EPMC8749934 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Local nerve inflammation (neuritis) leads to ongoing activity and axonal mechanical sensitivity (AMS) along intact nociceptor axons and disrupts axonal transport. This phenomenon forms the most feasible cause of radiating pain, such as sciatica. We have previously shown that axonal transport disruption without inflammation or degeneration also leads to AMS but does not cause ongoing activity at the time point when AMS occurs, despite causing cutaneous hypersensitivity. However, there have been no systematic studies of ongoing activity during neuritis or noninflammatory axonal transport disruption. In this study, we present the time course of ongoing activity from primary sensory neurons following neuritis and vinblastine-induced axonal transport disruption. Whereas 24% of C/slow Aδ-fiber neurons had ongoing activity during neuritis, few (<10%) A- and C-fiber neurons showed ongoing activity 1-15 days following vinblastine treatment. In contrast, AMS increased transiently at the vinblastine treatment site, peaking on days 4-5 (28% of C/slow Aδ-fiber neurons) and resolved by day 15. Conduction velocities were slowed in all groups. In summary, the disruption of axonal transport without inflammation does not lead to ongoing activity in sensory neurons, including nociceptors, but does cause a rapid and transient development of AMS. Because it is proposed that AMS underlies mechanically induced radiating pain, and a transient disruption of axonal transport (as previously reported) leads to transient AMS, it follows that processes that disrupt axonal transport, such as neuritis, must persist to maintain AMS and the associated symptoms. NEW & NOTEWORTHY Many patients with radiating pain lack signs of nerve injury on clinical examination but may have neuritis, which disrupts axonal transport. We have shown that axonal transport disruption does not induce ongoing activity in primary sensory neurons but does cause transient axonal mechanical sensitivity. The present data complete a profile of key axonal sensitivities following axonal transport disruption. Collectively, this profile supports that an active peripheral process is necessary for maintained axonal sensitivities.

Dataset Information

Characterizing the Mechanical Properties of Ectopic Axonal Receptive Fields in Inflamed Nerves and Following Axonal Transport Disruption.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets