Analgesic effect of highly reversible ω-conotoxin FVIA on N type Ca2+ channels
- Analgesic effect of highly reversible ω-conotoxin FVIA on N type Ca2+ channels
- 이승규; 김윤지; 백성근; 최희우; 이주연; 정현호; 류재하; 서홍원; 나흥식; 김현정; 임혜원; 김재일
- Issue Date
- Molecular pain
- VOL 6, 97-1-97-12
- Background: N-type Ca2+ channels (Cav2.2) play an important role in the transmission of pain signals to the
central nervous system. ω-Conotoxin (CTx)-MVIIA, also called ziconotide (Prialt？), effectively alleviates pain, without
causing addiction, by blocking the pores of these channels. Unfortunately, CTx-MVIIA has a narrow therapeutic
window and produces serious side effects due to the poor reversibility of its binding to the channel. It would thus
be desirable to identify new analgesic blockers with binding characteristics that lead to fewer adverse side effects.
Results: Here we identify a new CTx, FVIA, from the Korean Conus Fulmen and describe its effects on pain
responses and blood pressure. The inhibitory effect of CTx-FVIA on N-type Ca2+ channel currents was dosedependent
and similar to that of CTx-MVIIA. However, the two conopeptides exhibited markedly different degrees
of reversibility after block. CTx-FVIA effectively and dose-dependently reduced nociceptive behavior in the formalin
test and in neuropathic pain models, and reduced mechanical and thermal allodynia in the tail nerve injury rat
model. CTx-FVIA (10 ng) also showed significant analgesic effects on writhing in mouse neurotransmitter- and
cytokine-induced pain models, though it had no effect on acute thermal pain and interferon-g induced pain.
Interestingly, although both CTx-FVIA and CTx-MVIIA depressed arterial blood pressure immediately after
administration, pressure recovered faster and to a greater degree after CTx-FVIA administration.
Conclusions: The analgesic potency of CTx-FVIA and its greater reversibility could represent advantages over CTx-
MVIIA for the treatment of refractory pain and contribute to the design of an analgesic with high potency and low
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