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Dernière publication 27/05/2016

Cav1- 2 and Cav1- 3 l‐type calcium channels independently control short‐and long

Short-term central sensitization to pain temporarily increases the responsiveness of nociceptive pathways after peripheral injury. In dorsal horn...

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    [title] => Cav1- 2 and Cav1- 3 l‐type calcium channels independently control short‐and long
    [paragraph] => Cav1. 2 and Cav1. 3 l‐type calcium channels independently control short‐and long‐term sensitization to pain
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Authors
Radwani H, Lopez-Gonzalez MJ, Cattaert D, Roca-Lapirot O et al.

 Lab
University of Bordeaux, Bordeaux, France
Journal
J Physiol.
Abstract
Short-term central sensitization to pain temporarily increases the responsiveness of nociceptive pathways after peripheral injury. In dorsal horn neurons (DHNs), short-term sensitization can be monitored through the study of wind-up. Wind-up, a progressive increase in DHNs response following repetitive peripheral stimulations, depends on the post-synaptic L-type calcium channels. In the dorsal horn of the spinal cord, two L-type calcium channels are present, Cav1.2 and Cav1.3, each displaying specific kinetics and spatial distribution. In the present study, we used a mathematical model of DHNs in which we integrated the specific patterns of expression of each Cav subunits. This mathematical approach reveals that Cav1.3 is necessary for the onset of wind-up, whereas Cav1.2 is not and that synaptically triggered wind-up requires NMDA receptor activation. We then switched to a biological preparation in which we knocked down Cav subunits and confirmed the prominent role of Cav1.3 in both naive and spinal nerve ligation model of neuropathy (SNL). Interestingly, although a clear mechanical allodynia dependent on Cav1.2 expression was observed after SNL, the amplitude of wind-up was decreased. These results were confirmed with our model when adapting Cav1.3 conductance to the changes observed after SNL. Finally, our mathematical approach predicts that, although wind-up amplitude is decreased in SNL, plateau potentials are not altered, suggesting that plateau and wind-up are not fully equivalent. Wind-up and long-term hyperexcitability of DHNs are differentially controlled by Cav1.2 and Cav1.3, therefore confirming that short- and long-term sensitization are two different phenomena triggered by distinct mechanisms.
BIOSEB Instruments Used
Electronic Von Frey 4 (BIO-EVF4),Electronic Von Frey 5 with embedded camera (BIO-EVF5)
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Une solution rapide pour déterminer le seuil de sensibilité à la douleur mécanique chez les rongeurs (rats et souris). Maintenant en version sans-fil, pour être libéré des câbles!

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L'EVF5 intègre une caméra embarquée au niveau de la zone de stimulation et fonctionne avec un nouveau logiciel dédié révolutionnaire

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