How cone snail venom minimizes pain

This schematic shows the proposed mechanism by which the cone snail venom Vc1.1 reduces pain sensation through indirect inhibition of R-type (Cav2.3) neuronal voltage-gated calcium channels. Credit: Rittenhouse, 2014

The venom from marine cone snails, used to immobilize prey, contains numerous peptides called conotoxins, some of which can act as painkillers in mammals. A recent study in The Journal of General Physiology provides new insight into the mechanisms by which one conotoxin, Vc1.1, inhibits pain. The findings help explain the analgesic powers of this naturally occurring toxin and could eventually lead to the development of synthetic forms of Vc1.1 to treat certain types of neuropathic pain in humans.

Neuropathic , a form of that occurs in conjunction with injury to—or dysfunction of—the nervous system, can be debilitating and difficult to treat, and the medical community is eager to find better methods to minimize what can be a serious condition. Neuropathic pain is associated with changes in the transmission of signals between neurons, a process that depends on several types of voltage-gated calcium channels (VGCCs). However, given the importance of these VGCCs in mediating normal neurotransmission, using them as a pharmacological target against could potentially lead to undesirable side effects.

In previous studies, David Adams and colleagues from RMIT University in Melbourne showed that Vc1.1 acted against neuropathic pain in mice; they found that, rather than acting directly to block VGCCs, Vc1.1 acts through GABA type B (GABAB) receptors to inhibit N-type (Cav2.2) channels.

Now, Adams and colleagues show that Vc1.1 also acts through GABAB receptors to inhibit a second, mysterious class of neuronal VGCCs that have been implicated in pain signaling but have not been well understood—R-type (Cav2.3) channels. Their new findings not only help solve the mystery of Cav2.3 function, but identify them as targets for analgesic conotoxins.

More information: Article: Berecki, G., et al. 2014. J. Gen. Physiol. DOI: 10.1085/jgp.201311104
Commentary: Rittenhouse, A.R. 2014. J. Gen. Physiol. DOI: 10.1085.jgp.201411190

add to favorites email to friend print save as pdf

Related Stories

New insight into pain mechanisms

Apr 25, 2012

(Medical Xpress) -- Researchers in the UCL Wolfson Institute for Biomedical Research have made a discovery which could help the development of analgesic drugs able to treat nerve damage-related pain.

Putting the brakes on pain

Aug 05, 2013

Neuropathic pain—pain that results from a malfunction in the nervous system—is a daily reality for millions of Americans. Unlike normal pain, it doesn't go away after the stimulus that provoked it ends, and it also behaves ...

Possible safe and novel painkillers from tarantula venom

Feb 14, 2014

(Medical Xpress)—Screening more than 100 spider toxins, Yale researchers identified a protein from the venom of the Peruvian green velvet tarantula that blunts activity in pain-transmitting neurons. The ...

Recommended for you

New molecule sneaks medicines across the blood/brain barrier

45 minutes ago

Delivering life-saving drugs across the blood-brain barrier (BBB) might become a little easier thanks to a new report published in the November 2014 issue of The FASEB Journal. In the report, scientists describe an antibo ...

Clock gene dysregulation may explain overactive bladder

45 minutes ago

If you think sleep problems and bladder problems are a fact of life in old age, you may be right. A new report appearing in the November 2014 issue of The FASEB Journal, shows that our sleep-wake cycles are genetically connec ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.