Can the toxin produced by the anthrax causing bacterium offer a new way to silence pain? A new study from Harvard Medical School suggests the toxin normally associated with severe injury or death can block multiple types of pain.
To date this is based on studies in mice. However, the success of the work paves the way for further trials and a potential clinical study in humans.
Anthrax is a serious infectious disease caused by Gram-positive, rod-shaped bacteria known as Bacillus anthracis. The toxin produced by the bacterium can often lead to death (without treatment, only about 10 – 15 percent of patients with inhalation anthrax survive).
While the disease is more often associated with animals, humans are at risk if they come into contact with the organism. The disease can occur in four forms: skin, lungs, intestinal and injection, with direct contact being the primary route of infection.
With the new research, the findings indicate that the anthrax toxin can block multiple types of pain by targeting pain-sensing cells and altering signaling and blocking pain. This led to the development of an anthrax protein vehicle to deliver different types of treatments into pain receptors and to successfully modulate nerve-cell function. The anthrax toxin is delivered to the neurons of the central and peripheral nervous system.
The vast majority of research into microbial toxins examines how disease-causing bacteria interact with neurons and alter their signaling to amplify pain. Where the new study differs is the focus on using bacterial toxins to minimize or block pain.
The finding came about through an analysis of gene-expression data, which revealed that pain fibers of the dorsal root ganglia possess receptors for anthrax toxins, meaning they are structurally primed to interact with the anthrax bacterium.
The effect occurs when one of the proteins within the anthrax toxin called protective antigen (PA), binds to the nerve cell receptors forms a pore. The pore opens a gateway for two other bacterial proteins called edema factor (EF) and lethal factor (LF), to enter the nerve cell. The effect of the combined edema toxin alters the signaling inside nerve cells and ‘silence’ sensations of pain.
The activation of the pain silencing was demonstrated on experiments conducted on mice where the toxin was injected into the lower spines of mice. This demonstrably produced potent pain-blocking effects and prevented the rodents from sensing high-temperature and mechanical stimulations. Subsequent studies demonstrated how the toxin also alleviated symptoms of pain caused by inflammation and pain caused by nerve cell damage.
It is hoped the research will assist with the future design of drug therapies that can selectively target pain-sensing fibers. This would avoid the need for opioids and other addictive pain killers (which rewire the brain’s reward system). It may also be possible to design novel precision-targeted pain treatments that act on pain receptors.
The findings have been published in the journal Nature Neuroscience. The research paper is titled “Anthrax toxins regulate pain signaling and can deliver molecular cargoes into ANTXR2+ DRG sensory neurons.”
