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Thursday, October 17, 2013

Centipede venom to the rescue

If you suffer from chronic pain, there’s a good chance that your voltage-gated sodium channels are to blame. Humans have nine types of these channels, but one in particular, NaV1.7, is responsible for the sensation of some types of severe, episodic pain. I’ve explained the workings of NaV1.7 in a previous post, so go there for some background. 

This means that NaV1.7 would make an excellent target for an analgesic drug. That’s certainly what researchers led by Shilong Yang of the Chinese Academy of Sciences thought, and they have just the candidate: a protein found in centipede venom.

File:Scolopendra subspinipes mutilans1.jpg
Scolopendra subspinipes mutilans

Photo by KENPEI, Osaka, Japan, 6/28/09.
It turns out that venom of the Chinese red-headed centipede (Scolopendra subspinipes mutilans) includes a peptide (Ssm6a) that can block NaV1.7 sodium channels. Remember, as long as the channels are closed, you can’t feel any pain. The scientists were able to reversibly block the NaV1.7 channels in mice and in human cells grown in culture. More importantly, Ssm6a offered the mice substantial pain relief, as measured by the number of times some unfortunate mice licked their aching feet. In fact, Ssm6a was significantly more effective than morphine.

The effects of Ssm6a lasted several hours, probably until the peptide was cleared by liver and kidneys. Unlike other NaV1.7 blockers, Ssm6a has little or no effect on our other eight sodium channels, making it particularly appealing as a pain drug. Previously tried drugs were less specific, and thus could not be safely administered because blocking the other sodium channels can lead to paralysis, seizure or death.

Obviously there’s a long way to go between a mouse licking its paws and a new drug on the shelf. Still, the researchers are hopeful that Ssm6a will one day help to alleviate chronic, persistent pain.

Shilong Yanga, Yao Xiao, Di Kang, Jie Liu, Yuan Li, Eivind A. B. Undheim, Julie K. Klint, Mingqiang Rong, Ren Lai, & Glenn F. King (2013). Discovery of a selective NaV1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models Proceedings of the National Academy of Sciences of the United States of America DOI: 10.1073/pnas.1306285110.