Suppression of inflammatory and neuropathic pain symptoms in mice lacking the N-type Ca2+ channel.
The importance of voltage-dependent Ca2+ channels (VDCCs) in pain transmission has been noticed gradually, as several VDCC blockers have been shown to be effective in inhibiting this process. In particular, the N-type VDCC has attracted attention, because inhibitors of this channel are effective in various aspects of pain-related phenomena. To understand the genuine contribution of the N-type VDCC to the pain transmission system, we generated mice deficient in this channel by gene targeting. We report here that mice lacking N-type VDCCs show suppressed responses to a painful stimulus that induces inflammation and show markedly reduced symptoms of neuropathic pain, which is caused by nerve injury and is known to be difficult to treat by currently available therapeutic methods. This finding clearly demonstrates that the N-type VDCC is essential for development of neuropathic pain and, therefore, controlling the activity of this channel can be of great importance for the management of neuropathic pain.
Saegusa
H
H
Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental University and CREST, Japan Science and Technology Corporation, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Kurihara
T
T
Zong
S
S
Kazuno
A
A
Matsuda
Y
Y
Nonaka
T
T
Han
W
W
Toriyama
H
H
Tanabe
T
T
D019342:Acetic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D000161:Acoustic Stimulation; D000818:Animals; D001007:Anxiety / Q000209:etiology; D001522:Behavior, Animal; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000235:genetics / Q000502:physiology*; D005557:Formaldehyde / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D005727:Ganglia, Spinal / Q000166:cytology; D018390:Gene Targeting; D006930:Hyperalgesia / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D009474:Neurons / Q000187:drug effects; D009619:Nociceptors; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D010487:Periaqueductal Gray / Q000378:metabolism; D013127:Spinal Nerves / Q000293:injuries; D020867:omega-Agatoxin IVA / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020867:omega-Agatoxin IVA; D005557:Formaldehyde; D019342:Acetic Acid