There's renewed hope that a venom compound from the South American rattlesnake could one day be used to ease chronic pain, after scientists have found a way to reduce its toxicity while boosting the compound's analgesic properties.
Crotoxin, found in the venom of this rattlesnake species (Crotalus durissus ssp. terrificus), is already well known for being an anti-inflammatory painkiller, and a muscle paralyser. But it's also exceedingly toxic. The new study shows that crotoxin could be made less deadly by packing it in a SBA-15 silica nanostructure.
Based on tests on animals, this silica-contained crotoxin could offer some hope for the millions of people living with neuropathic pain, which is where damaged nerves or a faulty nervous system cause stinging or burning sensations. Common painkillers often have no effect on this type of nerve pain.
"I've been studying crotoxin since 2011," pharmacologist Gisele Picolo told news agency Agência FAPESP. "The results are positive in terms of its analgesic effect, but its toxicity has always been a constraint."
"Using silica was a great idea. This is the first time the two molecules have been combined."
SBA-15 silica is a type of porous nanomaterial originally developed for vaccine production – it can help to slow down the chemical reaction triggered by a vaccine, so that enough antibodies are produced. Here, it's protecting against toxins.
Experiments on mice with a condition similar to neuropathic pain found that once the SBA-15 silica nanostructure was added, more crotoxin could be applied before side effects were noticed.
Further tests showed the pain-killing effects of crotoxin lasting longer with the addition of SBA-15 silica. In one test, a single dose was enough to reverse hypernociception (the heightened sensitivity to painful stimuli) for 48 hours.
By examining individual pain receptors in the mice, the scientists were able to determine that the addition of the SBA-15 nanostructure wasn't changing the mechanisms crotoxin uses to relieve pain. What's more, the silica prevents the breakdown of the compound in the stomach, which means it can be administered orally.
The early signs are very promising, but we're still a long way from a crotoxin-inspired painkiller – not least because we have no easy way of synthesising it en masse in the lab, despite some recent advances in this area.
"Crotoxin is a large molecule with a complex structure that's hard to replicate in the laboratory, so scaled-up use is a long way off," says Picolo.
Work continues to try and get this available as a drug suitable for humans, with all the therapeutic benefits of crotoxin and as little of the toxicity as possible - and this latest development is certainly an encouraging step forward.
The research has been published in Toxins.