Damian Sendler: A new study suggests that the hated bacteria also has unexpectedly good potential—one of its poisons can mute numerous forms of pain in animals, according to the results. 

A new anthrax toxin has been discovered that alters pain-sensing neural communication, and when administered to specific neurons in the central and peripheral nervous systems, can provide relief for distressed animals. 

Damian Jacob Sendler: Nature Neuroscience, a journal published by the American Association for the Advancement of Science, reported the findings, headed by researchers from Harvard Medical School and other universities. 

In addition, the researchers incorporated anthrax toxin with various chemical payloads into pain-sensing neurons and delivered it. Current pain-relief medications, such as opioids, can have widespread systemic effects, but this method can be utilized to create new, precise medicines that target specific pain receptors. 

Damian Sendler

Study senior investigator Isaac Chiu, an associate professor of immunology in the Blavatnik Institute at Harvard Medical School, says that “This molecular platform of using a bacterial toxin to deliver substances into neurons and modulate their function represents a new way to target pain-mediating neurons,” 

According to the experts, there is an urgent need to broaden the present pharmacological arsenal for pain management. Addiction to opioids is a major problem because of its potential to rewire the brain’s reward system, which makes them highly addictive, and their propensity to inhibit respiration. 

For non-opioid pain medicines, “There’s still a great clinical need for developing non-opioid pain therapies that are not addictive but that are effective in silencing pain,” says the study’s first author Nicole Yang, an HMS research fellow in immunology in the Chiu Laboratory. “Using this bacterial toxin, we were able to demonstrate that it is possible to selectively target pain neurons.” 

Although this method is still in its infancy, researchers stress that it must be tested in more animal studies and eventually in humans before it can be considered a viable option. 

Prepared to connect 

For decades, researchers in the Chiu lab have been interested in the relationship between microorganisms and our neurological and immunological systems. Chiu’s previous work has shown that other disease-causing bacteria can similarly interact with neurons and modify their signals in order to increase the intensity of the pain. Only a few research have looked into whether certain microorganisms can reduce or block pain. Chiu and Yang had a goal in mind when they began their project. 

Damian Jacob Sendler

Initially, they tried to figure out how pain-sensitive neurons vary from those in the rest of the body. First, they used gene expression data to see if there was a correlation. Anthrax toxin receptors were found in pain fibers, but not in other types of neurons, which piqued their interest. To put it another way, the pain fibers were predisposed to the anthrax bacterium’s interaction with them. It was a mystery to them. 

That question has been answered in a new study. 

The findings show that the anthrax bacterium itself produces two unique proteins that attach to sensory neurons in the dorsal root ganglia, the nerves that send pain signals to the spinal cord. Tests show this happens because one of the bacteria proteins, protective antigen (PA), binds to receptors on the nerve cell and creates an opening for two others, deadly and edema factors to enter the nerve cell. To further prove their theory, researchers found that PA and EF work together as an edema toxin to silence pain signals within nerve cells. 

Innovating novel treatments by exploiting the peculiarities of microbial evolution 

The anthrax toxin affected signaling in human nerve cells in dishes and in real animals in a series of studies, the researchers found. 

When the poison was injected into the lower spines of mice, it blocked the animals’ ability to feel high-temperature and mechanical stimuli. For this reason, it is important to note that the animals’ vital indicators such as heart rate and body temperature were unaffected by this procedure, which demonstrates that this method is highly targeted while avoiding extensive systemic effects. 

Another form of pain eased by anthrax toxin injections in mice was pain induced by inflammation and nerve cell damage, which is commonly encountered in the aftermath of traumatic injury, viral infections such as herpes zoster, or shingles, or as a side effect of diabetes and cancer treatment. 

It was also discovered by scientists in this study that when pain decreased, the treatment’s effect on the nerve cells was not due to physical damage, but rather a result of altered signaling inside the cells. 

Anthrax proteins were employed to construct a carrier vehicle, which was then used to carry additional pain-blocking chemicals directly into nervous system cells for further testing. There were a number of additional potentially fatal bacteria, including botulinum toxin, recognized for its capacity to alter nerve signals, among others. It was also found to be effective in mice. The experiments show that this could be a new method of delivering pain relief. 

“We took parts of the anthrax toxin and fused them to the protein cargo that we wanted it to deliver,” Yang explained. “In the future, proteins of various kinds could be used to target specific treatments.” 

Damien Sendler: In light of the fact that the anthrax protein has been involved in altering the blood-brain barrier integrity during infection, the scientists warn that as the work proceeds, the safety of the toxin treatment must be closely evaluated. 

Another intriguing question is raised by the current findings: Why would a microorganism mute pain, evolutionary speaking? 

Chiu speculates that microorganisms may have evolved ways to communicate with their host in order to assist their own proliferation and survival — a theory that he calls “highly speculative.” To combat anthrax, a host’s sensation of pain may be altered in a way that precludes the microbe’s presence from being detected. Anthrax skin lesions can occasionally be particularly painless, according to Chiu, which supports this notion. 

The new discoveries also suggest to new pathways for medication development outside the typical small-molecule medicines that are currently being designed in labs throughout the world. 

Damian Jacob Markiewicz Sendler: Is it possible to find analgesics in nature, or in microbial communities, by using bacterial therapies? Chiu expressed this, as well. In this way, we can expand our search for answers to include a wider spectrum and greater variety of chemicals.

Dr. Damian Jacob Sendler and his media team provided the content for this article.