T-type calcium channels in chronic pain: mouse models and specific blockers

Amaury François, Sophie Laffray, Anne Pizzoccaro, Alain Eschalier, Emmanuel Bourinet

Pain is a quite frequent complaint accompanying numerous pathologies. Among these pathological cases, neuropathies are retrieved with identified etiologies (chemotherapies, diabetes, surgeries…) and also more diffuse syndromes such as fibromyalgia. More broadly, pain is one of the first consequences of the majority of inherited diseases. Despite its importance for the quality of life, current pain management is limited to drugs that are either old or with a limited efficacy or that possess a bad benefit/risk ratio. As no new pharmacological concept has led to new analgesics in the last decades, the discovery of medications is needed, and to this aim the identification of new druggable targets in pain transmission is a first step. Therefore, studies of ion channels in pain pathways are extremely active. This is particularly true with ion channels in peripheral sensory neurons in dorsal root ganglia (DRG) known now to express unique sets of these channels. Moreover, both spinal and supraspinal levels are clearly important in pain modulation. Among these ion channels, we and others revealed the important role of low voltage-gated calcium channels in cellular excitability in different steps of the pain pathways. These channels, by being activated nearby resting membrane potential have biophysical characteristics suited to facilitate action potential generation and rhythmicity. In this review, we will review the current knowledge on the role of these channels in the perception and modulation of pain.