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Comment
. 2025 Feb 17;135(4):e189308.
doi: 10.1172/JCI189308.

The N-type calcium channel rises from the ashes

Maria A Gandini, Gerald W Zamponi
Comment

The N-type calcium channel rises from the ashes

Maria A Gandini et al. J Clin Invest. .

Abstract

Chronic pain is a debilitating condition that affects up to 1.5 billion people globally. Advancing pain management depends on a thorough understanding of the types of pain experienced by patients and the underlying mechanisms driving it. N-type calcium channels play a crucial role as therapeutic targets for managing chronic pain. In this issue of the JCI, Tang et al. introduce C2230, an N-type calcium channel blocker that inhibited CaV2.2 channels during high frequency stimulation with little effect on other ion channels in the pain pathway across multiple models. C2230 offers a promising analgesic for use in therapeutic intervention.

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Conflict of interest statement

Conflict of interest: GWZ is cofounder and chief Scientific officer of Zymedyne Therapeutics (Calgary, Alberta, Canada). GWZ holds numerous patents pertaining to calcium channel blocking analgesics, the numbers and titles of which are available in the Supplemental Materials.

Figures

Figure 1
Figure 1. C2230 blocks N-type calcium channel and inhibits pain.
N-type calcium channels are expressed in the primary afferent pathways that innervate the skin, originating from dorsal root ganglion (DRG) neurons and their synaptic nerve terminals in the spinal dorsal horn. C2230 given to rodents using any of three different routes prevented calcium entry via CaV2.2 N-type calcium channels. The treatment led to analgesia of pain in three pain models.
See this image and copyright information in PMC

Comment on

  • C2230, a preferential use- and state-dependent CaV2.2 channel blocker, mitigates pain behaviors across multiple pain models

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