Anthrax analgesic
The anthrax bacterium is widely known as the cause of severe lung diseases and frightening, albeit painless, skin lesions. The results of a new study show that it also has an unexpected therapeutic potential – one of the Bacillus anthracis toxins can extinguish several types of pain in animals.
This specific anthrax toxin alters the transmission of signals from pain receptors to neurons.
A team led by Harvard Medical School researchers combined parts of anthrax toxin with various types of exogenous molecules, and delivered these combined molecules to pain-sensitive receptors. This method can be used to develop new high-precision pain treatments that affect pain receptors, but without the widespread systemic effects of modern painkillers, including opioids.
Currently, opioids remain the most effective painkillers, but they have dangerous side effects, primarily the ability to change the brain's reward system, which causes severe dependence. In addition, opioids tend to suppress breathing and can be fatal.
Thus, there is a great clinical need to develop non-opioid pain treatments that are not addictive, but are effective enough to suppress pain. One of the strategies, at least experimentally, may be targeted exposure to pain neurons using anthrax toxin.
The group began its research with an attempt to determine how pain-sensitive neurons can differ from other neurons in the human body. Analysis of gene expression revealed one curious feature: the processes of pain neurons had receptors for anthrax toxins, while other types of neurons did not have them. In other words, the pain fibers are structurally ready to interact with the anthrax bacterium.
A recently published study explains this phenomenon. Pain suppression occurs when the sensitive neurons of the spinal cord ganglia, which transmit pain signals to the spinal cord, interact with two specific proteins produced by the anthrax bacterium. Experiments have shown that one of the bacterial proteins – protective antigen (PA) – binds to nerve cell receptors and forms a pore that serves as a gateway for two other bacterial proteins: edema factor (EF) and lethal factor (LF), which must be transferred to the nerve cell. The study also demonstrated that PA and EF, collectively known as edema toxin, alter the transmission of signals inside nerve cells, leading to pain suppression.
In a series of experiments, the researchers found that anthrax toxin alters the transmission of signals in human nerve cells in vitro, as well as in living animals.
The introduction of the toxin into the lower spine of mice led to a powerful analgesic effect, preventing the animals from perceiving temperature and mechanical stimuli. It is important to note that other vital signs of the animals, such as heart rate, body temperature and coordination of movements, were not affected. This proves that the new method was selective and accurate in targeting pain fibers and blocking pain without systemic effects.
In addition, injecting mice with anthrax toxin relieved the symptoms of two other types of pain: pain caused by inflammation and pain caused by nerve cell damage, often seen after injury, certain viral infections (shingles) or as a complication of diabetes and cancer treatment.
The researchers also noticed that as the pain decreased, the nerve cells continued to function, which means that the effects of blocking pain were caused not by damage to the nerve cells, but by a change in the signals inside them.
At the final stage, the group developed a carrier from anthrax proteins and used it to deliver other pain-blocking substances to nerve cells. One of them was botulinum toxin, a protein complex of another potentially deadly bacterium known for its ability to alter neural transmission. This approach also led to pain relief in mice.
Scientists warn that it is necessary to carefully monitor the safety of treatment with toxins, especially considering that anthrax protein is capable of violating the integrity of the blood-brain barrier.
The results raise another interesting question: why, from an evolutionary point of view, a dangerous microorganism can drown out pain?
Perhaps one explanation is that the bacteria have developed ways of interacting with the host to facilitate their own spread and survival. In the case of anthrax, this adaptive mechanism may be associated with altered signaling that blocks the host's ability to feel pain and, consequently, the presence of the bacterium. This hypothesis explains why the skin lesions that the anthrax bacterium forms are so painless.
Article I.Chiu et al. Anthrax toxins regulate pain signaling and can deliver molecular cargos into Antxr2+ DRG sensory neurons is published in the journal Nature Neuroscience.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on materials from Harvard Medical School: Can a Dangerous Microbe Quell Pain?