Details

Autor(en) / Beteiligte

• Belkouch, Mounir
• Dansereau, Marc-Andre
• Tetreault, Pascal
• Biet, Michael
• Beaudet, Nicolas
• Dumaine, Robert
• Chraibi, Ahmed
• Melik-Parsadaniantz, Stephane
• Sarret, Philippe

Titel

Functional up-regulation of Na sub(v)1.8 sodium channel in A[beta] afferent fibers subjected to chronic peripheral inflammation

Ist Teil von

• Journal of neuroinflammation, 2014-01, Vol.11 (1), p.45-45

Erscheinungsjahr

2014

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Background: Functional alterations in the properties of A[beta] 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 sub(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 sub(v)1.8 in controlling A[beta]-fiber excitability following persistent inflammation. Methods: Distribution and expression of Na sub(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 I sub(Na) and TTX-R Na sub(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 sub(v)1.8-preferring blocker on the electrophysiological properties of Na sub(v)1.8 currents and on the mechanical sensitivity and inflammation of the hind paw in CFA-treated rats. Results: Our findings revealed that Na sub(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 I sub(Na) and Na sub(v)1.8 peak current densities are enhanced in inflamed large myelinated A[beta]-fiber neurons. Persistent inflammation leading to nociception also induced time-dependent changes in A[beta]-fiber neuron excitability by shifting the voltage-dependent activation of Na sub(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 sub(v)1.8 currents in A[beta]-fiber neurons observed following intraplantar CFA injection and concomitantly blocks CFA-induced mechanical allodynia, suggesting that Na sub(v)1.8 regulation in A[beta]-fibers contributes to inflammatory pain. Conclusions: Collectively, these findings support a key role for Na sub(v)1.8 in controlling the excitability of A[beta]-fibers and its potential contribution to the development of mechanical allodynia under persistent inflammation.