Voltage-gated calcium channels as targets for the treatment of chronic pain.
This review focuses on the importance of voltage-gated calcium channels in modulating and controlling the function of peripheral and central neurons involved in nociceptive processing. We describe the different families of voltage-gated calcium channels that are expressed in pain pathway neurons, how the expression levels of calcium channel currents change in chronic pain conditions, and the validation of N-type, T-type, and P-type calcium channels as targets for the treatment of pain. The molecular mechanism of action is reviewed for the most prominent calcium channel-targeted drugs including gabapentin and ziconotide as well as antiepileptics administered off-label for the treatment of pain. We discuss how the major genetic, functional, and pharmacological differences between subtypes of neuronal calcium channels can be leveraged to identify new molecular targets and to discover and develop new therapeutic agents for the treatment of chronic pain syndromes.
McGivern
Joseph G
JG
Department of HTS-Molecular Pharmacology, Amgen Inc., Thousand Oaks, California 91320, USA. mcgivern@amgen.com
McDonough
Stefan I
SI
D000344:Afferent Pathways / Q000187:drug effects / Q000503:physiopathology*; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D015220:Calcium Channels / Q000187:drug effects / Q000235:genetics*; D015195:Drug Design; D006801:Humans; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010148:Intractable Pain / Q000188:drug therapy / Q000503:physiopathology*
D000700:Analgesics; D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D015220:Calcium Channels