Voltage gated calcium channels as targets for analgesics.
Management of pain is an essential aspect of medicine; however, current therapies are frequently insufficient owing to severe side effects or limited effectiveness. Therefore, the discovery of new analgesics is needed, especially to treat the proportion of painful patients poorly improved by available analgesics. The transmission of nociceptive stimuli in primary afferent neurons critically depends on a peculiar repertoire of various types of ion channels such as a number of TRP channels, persistent sodium channels, inwardly rectifying potassium channels and voltage-gated calcium channels that either detect noxious stimuli, or regulate cellular excitability and synaptic transmission. Moreover, some of these channels are redistributed and upregulated in pathological states leading to abnormal detection or transmission of harmful stimuli, and consequently lead to states of chronic pain. Hence, these channels are considered key targets for the development of analgesics. The nervous system expresses multiple types of calcium channels with specialized roles in neurophysiology. Here, we review the role of these channels and their accessory subunits in nociceptive signaling, and their potential as targets for development of innovative analgesics.
Bourinet
Emmanuel
E
Département de Physiologie, Institut de Génomique Fonctionnelle CNRS UMR5203, INSERM U661, Universités Montpellier I & II, 141 Rue de la Cardonille, 34094 Montpellier Cedex 5, France.
Zamponi
Gerald W
GW
D000700:Analgesics / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D020864:Calcium Channels, N-Type / Q000502:physiology*; D020747:Calcium Channels, T-Type / Q000502:physiology*; D015195:Drug Design; D010146:Pain / Q000188:drug therapy*
D000700:Analgesics; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020747:Calcium Channels, T-Type