Rattlesnake (Crotalus adamanteus) is the largest venomous snake in North America, reaching 8 feet and weighing up to 10 pounds. In the past, medical experts believed that the toxin in rattlesnake venom, crotoxin, could be a promising compound for the treatment of chronic pain.
Eastern Diamondback rattlesnake (Crotalus adamanteus). Image Credit: Belizar / Shutterstock
The toxicity of crotoxin limits its medicinal use; hence, scientists took a long while before finding a new way to use the toxin in treating various diseases. Now, a team of scientists has found a way to limit its toxicity and enhance its therapeutic effects.
In the study published in the journal Toxins, the scientists found that encapsulating the toxin in a nanostructures SBA-15 silica, which is a material developed for vaccine formulations, can help in delivering the compound into the body, without inducing a poisonous effect.
The researchers, who were part of Brazil’s National Science and Technology Institute (INCT) on Toxins in São Paulo State, in coordination with the National Council for Scientific and Technological Development (CNPq), wanted to determine if crotoxin is effective for neuropathic pain, which is caused by structural and functional plasticity in sensory pathways, producing impairments in nociceptive processing.
Currently, treating the condition remains a challenge in the medical world. The team found that crotoxin is a promising new way to treat the condition for its prolonged anti-inflammatory and antinociceptive effects.
The team wanted to limit the compound’s toxicity by using SBA-15, an inert nanostructured mesoporous silica to be used as a vehicle. The researchers studied the concept of mice to see how the antibodies react to the toxin. The team used SBA-15, the mesoporous silica, which is used in vaccines to augment the host’s antigen-specific immune response.
In vaccinations, some people react differently, wherein the body may react to the vaccine antigen introduced and release macrophages that can catabolize the antigen very quickly, limiting the time for lymphocytes to induce a complete response in producing antibodies. However, nanostructures silica slows the activity of macrophages.
In the current study, the team wanted to test if it works the same in the venom toxin, but in terms of reducing its toxic effects. The mice in the study produced more antibodies against an antigen when it was combined with silica. Meanwhile, when the silica was tested with other toxins, the team found a new protective effect. They concluded that the silica makes antigens less potent and may help reduce the adverse effect of the diphtheria toxin.
“I’ve been studying crotoxin since 2011. 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,” Gisele Picolo, lead investigator, said.
What is neuropathic pain?
Neuropathic pain is a chronic pain that results from a disease affecting the somatosensory nervous system. In patients with this type of pain, they experience abnormal sensations dubbed as dysesthesia or pain from normally non-painful stimuli (allodynia). Some patients may experience chronic pain, while others suffer from episodic attacks.
The condition affects peripheral fibers and central neurons, experienced by about 7 to 10 percent of the general population. There are many causes of neuropathic pain, including aging, diabetes mellitus, and chemotherapy.
At present, neuropathic pain is common but poorly treated. The management of the condition includes using tricyclic antidepressants or serotonin or noradrenaline reuptake inhibitors (SSRI). In some cases, patients receive tramadol or topical lidocaine, and in more severe patients, stronger opioids are used.
The condition dramatically impairs quality of life; hence, many studies focus on finding a promising treatment for chronic pain.
Sant’Anna, M., Lopes, S.R., Kimura, L.F., Giardini, C., Sant’Anna, O.A., and Picolo, G. (2020). Crotoxin Conjugated to SBA-15 Nanostructured Mesoporous Silica Induces Long-Last Analgesic Effect in the Neuropathic Pain Model in Mice. Toxins. https://www.mdpi.com/2072-6651/11/12/679/htm