Cone Shell Toxins May Ease Pain
Peptides from Poisonous Cone Snails Could Create New Analgesics
Nov 2, 2008
Australian neuroscientist Professor David Adams and his team at the Queensland Brain Institute have identified specific peptides, or mini-proteins, in the cone shell toxin that may serve as the molecular framework for novel ‘designer’ analgesics.
Chronic Pain from Nerve Damage Hard to Relieve
People suffering from chronic or neuropathic pain find it difficult to get relief by using everyday analgesic medications, as these do not prevent the uncontrolled activation of pain pathways caused by nerve damage.
However, the venom that the poisonous cone shell snail injects by a harpoon-like organ into the fish, molluscs and worms that are its prey, contains what Dr Adams calls “ a cocktail of 100-200 peptides”, many of which "block the membrane receptors and ion channels in pain pathways.”
Conus species are found in marine habitats all around the world, and the toxins have been studied by Dr Adams and other neuroscientists for at least a decade.
“For several years, it's been known that the remarkable properties of cone shell toxins (conotoxins) hold tremendous promise for chronic pain sufferers, and drugs that can combat or alleviate pain are a holy grail in drug discovery,” he said.
A New Approach to Conotoxins as Analgesics
Most researchers believe that conotoxins work to relieve pain by blocking the calcium ion channel in the animal or person’s neurotransmitters.
While there is already at least one possible novel pain medication developed from omega-conotoxins under consideration by the US FDA for treatment of chronic or intractable pain, Dr Adams and his colleagues challenge the view that the method these conotoxins use to block calcium ion channels is the only way to prevent neuropathic pain.
In a paper published in the October 22, 2008 Journal of Neuroscience, Professor Adams and colleagues, including Professor David Craik from UQ's Institute for Molecular Bioscience, have described a new way of inhibiting pain sensors using mini-proteins commonly found in cone snail venoms.
They claim that having only one model of the way conotoxins prevent the neurotransmission of pain, is like finding only one thread in a complex pattern.
“The conotoxins Vc1.1 and Rg1A, which have been shown in animal pain models to be analgesic, were thought to act by blocking nicotinic acetylcholine receptors, whereas we have shown that these peptides are 100-fold more potent at inhibiting calcium channels via GABA-B receptor activation,” Dr Adams said.
“This is potentially a new target for conotoxins to block pain transmission, and could be a paradigm shift in the development of conotoxin-based therapeutics and analgesics.”
Conotoxins a Paradigm Shift In Pain Relief
What does this mean for sufferers of chronic or neuropathic pain?
Dr Adams explained that recognising that alpha-conotoxin Vc1.1 is 100 times more effective at inhibiting neuronal calcium channels when aimed at the GABA-B receptor means a better likelihood of pain relief from these natural toxins.
“It has been known for some time that GABA-B receptor agonists such as baclofen are analgesic but are not used because of the adverse side-effects,” he said.
"The mechanism that we propose for Vc1.1 and Rg1A in inhibiting calcium channels and therefore pain transmission is analogous to the opioids which act via opioid receptors to inhibit calcium channels."
He foresaw a whole new class of analgesic drugs and therapies being developed from cone shell toxins over the next couple of decades.
“It is most likely that there are other peptides derived from cone snail venoms that may have therapeutic potential,” he said.
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