[Involvement of N-type calcium channels in pain and antinociception].
N-type voltage-dependent calcium channels are critical for pain transduction and modulation. These channels are highly present at the presynaptic terminals of nociceptive neurons in dorsal horn of the spinal cord where they regulate the release of the key pro-nociceptive neurotransmitters such as glutamate and substance P. Consistent with this, the selective blockers of the N-type channels are powerful analgesics, and, mice lacking the N-type Ca(v)2. 2 subunit have higher pain thresholds compared to wild-type. The N-type channels are also present at synapses in the autonomic system and the central nervous system, the inhibition of these synapses is the main reason of the side effects in analgesic therapy with current N-type channel blockers. Recently, a unique splice isoform of the N-type channels was found exclusively expressed at the nociceptive neurons in dorsal root ganglia, which may represent a novel target for pain management.
Wen
Lei
L
Beijing Institution of Pharmacology & Toxicology.
Yang
Sheng
S
Zhou
Wen-Xia
WX
Zhang
Yong-Xiang
YX
Zhou
Xiao-Wei
XW
Huang
Pei-Tang
PT
D000818:Animals; D020864:Calcium Channels, N-Type / Q000502:physiology*; D005727:Ganglia, Spinal / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D009619:Nociceptors / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D017288:Pain Threshold; D013373:Substance P / Q000378:metabolism
D020864:Calcium Channels, N-Type; D013373:Substance P; D018698:Glutamic Acid