Centrally expressed Cav3.2 T-type calcium channel is critical for the initiation and maintenance of neuropathic pain

Sophie L Fayad (1, 2, 3) , Guillaume Ourties (4, 5) , Benjamin Le Gac (1, 6, 3) , Baptiste Jouffre (4, 5) , Sylvain Lamoine (4, 5) , Antoine Fruquière (7) , Sophie Laffray (7) , Laila Gasmi (1, 8, 3) , Bruno Cauli (1, 6, 3) , Christophe Mallet (4, 5) , Emmanuel Bourinet (7) , Thomas Bessaih (1, 2, 3) , Régis C Lambert (1, 2, 3) , Nathalie Leresche (1, 2, 3)

1 NPS - Neuroscience Paris Seine
2 NPS - Réseaux de neurones et rythmes physiopathologiques = Neuronal Networks and Physiopathological Rhythms
3 IBPS - Institut de Biologie Paris Seine
4 Neuro-Dol - Neuro-Dol
5 Institut Analgesia
6 NPS - Réseau cortical et couplage neurovasculaire = Cortical Network and Neurovascular
7 IGF - Institut de Génomique Fonctionnelle
8 NPS - Signalisation Neuronale et Régulations Géniques = Neuronal Signaling and Gene Regulation

Cav3.2 T-type calcium channel is a major molecular actor of neuropathic pain in peripheral sensory neurons, but its involvement at the supraspinal level is almost unknown. In the anterior pretectum (APT), a hub of connectivity of the somatosensory system involved in pain perception, we show that Cav3.2 channels are expressed in a subpopulation of GABAergic neurons coexpressing parvalbumin (PV). In these PV-expressing neurons, Cav3.2 channels contribute to a high-frequencybursting activity, which is increased in the spared nerve injury model of neuropathy. Specific deletion of Cav3.2 channels in APT neurons reduced both the initiation and maintenance of mechanical and cold allodynia. These data are a direct demonstration that centrally expressed Cav3.2 channels also play a fundamental role in pain pathophysiology. Editor's evaluation The manuscript shows an important role for Cav2.3 channels in SNI-mediated allodynia and the firing properties of PV-expressing APT neurons. Mechanisms that underlie adaptations in chronic pain models are extremely important for the development of novel therapeutics for chronic pain and this could be a significant contribution in that regard.

Domaines: Sciences du Vivant [q-bio]

Sophie L Fayad, Guillaume Ourties, Benjamin Le Gac, Baptiste Jouffre, Sylvain Lamoine, et al.. Centrally expressed Cav3.2 T-type calcium channel is critical for the initiation and maintenance of neuropathic pain. eLife, 2022, 11, pp.e79018. ⟨10.7554/elife.79018⟩. ⟨hal-03942925⟩