Dataset Information


Functional up-regulation of Nav1.8 sodium channel in A? afferent fibers subjected to chronic peripheral inflammation.

ABSTRACT: BACKGROUND: Functional alterations in the properties of A? afferent fibers may account for the increased pain sensitivity observed under peripheral chronic inflammation. Among the voltage-gated sodium channels involved in the pathophysiology of pain, Na(v)1.8 has been shown to participate in the peripheral sensitization of nociceptors. However, to date, there is no evidence for a role of Na(v)1.8 in controlling A?-fiber excitability following persistent inflammation. METHODS: Distribution and expression of Na(v)1.8 in dorsal root ganglia and sciatic nerves were qualitatively or quantitatively assessed by immunohistochemical staining and by real time-polymerase chain reaction at different time points following complete Freund's adjuvant (CFA) administration. Using a whole-cell patch-clamp configuration, we further determined both total INa and TTX-R Na(v)1.8 currents in large-soma dorsal root ganglia (DRG) neurons isolated from sham or CFA-treated rats. Finally, we analyzed the effects of ambroxol, a Na(v)1.8-preferring blocker on the electrophysiological properties of Nav1.8 currents and on the mechanical sensitivity and inflammation of the hind paw in CFA-treated rats. RESULTS: Our findings revealed that Na(v)1.8 is up-regulated in NF200-positive large sensory neurons and is subsequently anterogradely transported from the DRG cell bodies along the axons toward the periphery after CFA-induced inflammation. We also demonstrated that both total INa and Na(v)1.8 peak current densities are enhanced in inflamed large myelinated A?-fiber neurons. Persistent inflammation leading to nociception also induced time-dependent changes in A?-fiber neuron excitability by shifting the voltage-dependent activation of Na(v)1.8 in the hyperpolarizing direction, thus decreasing the current threshold for triggering action potentials. Finally, we found that ambroxol significantly reduces the potentiation of Na(v)1.8 currents in A?-fiber neurons observed following intraplantar CFA injection and concomitantly blocks CFA-induced mechanical allodynia, suggesting that Na(v)1.8 regulation in A?-fibers contributes to inflammatory pain. CONCLUSIONS: Collectively, these findings support a key role for Na(v)1.8 in controlling the excitability of A?-fibers and its potential contribution to the development of mechanical allodynia under persistent inflammation.

SUBMITTER: Belkouch M 

PROVIDER: S-EPMC4007624 | BioStudies | 2014-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2011-01-01 | S-EPMC3091880 | BioStudies
2012-01-01 | S-EPMC3411591 | BioStudies
2010-01-01 | S-EPMC2978671 | BioStudies
2019-01-01 | S-EPMC6529352 | BioStudies
2018-01-01 | S-EPMC6237221 | BioStudies
2015-01-01 | S-EPMC4687803 | BioStudies
2012-01-01 | S-EPMC3330728 | BioStudies
2016-01-01 | S-EPMC4939223 | BioStudies
1000-01-01 | S-EPMC5666337 | BioStudies
2016-01-01 | S-EPMC4737776 | BioStudies