Harvard Medical School scientists have discovered certain factors in the toxins produced by anthrax bacteria that can shut down the activity of pain-signaling neurons, suggesting this could be a new model for future pain relief therapies.
The disease’s toxin can be lethal but has the effect of blocking pain sensation
The anthrax toxin consists of several molecules secreted by anthrax bacteria. Each type of protein is non-toxic on its own, but when combined, they can become deadly. This new study aims to understand how these anthrax toxins affect neurons in the brain.
The common characteristic of anthrax is black skin lesions.
The research found that pain-sensing neurons in the dorsal root ganglia (DRG) seem to carry high-affinity receptors for binding with anthrax toxins. Through a series of impressive experiments, the researchers demonstrated precisely how two specific types of anthrax proteins alter signaling within the neurons.
There are two types of anthrax toxins – edema toxin and lethal toxin. Both toxins share a crucial protein called PA (protective antigen). PA is likened to a “Trojan horse”, facilitating the entry of edema factor (EF) or lethal factor (LF) proteins into the cells.
The new study convincingly demonstrated how the edema toxin (comprising PA and EF) can selectively target and silence pain-signaling neurons in the dorsal root ganglia. Experiments in mice showed that when these two types of proteins were injected into the animals’ spinal cords, they effectively acted on specific neurons in the brain and blocked pain sensation.
Dr. Isaac Chiu, the senior investigator of the study, stated: “This molecular platform uses bacterial toxins to deliver substances into neurons and modulate their function, representing a novel approach to target pain-inducing intermediary neurons.”
Dr. Nicole Yang, a co-author, explained: “We took parts of the anthrax toxin and combined them with proteins that we wanted it to transport. In the future, we may discover more different types of proteins to provide targeted treatment methods.”
Of course, this type of research is still in its early stages and will require much more work before a potential new therapy can transition from the laboratory to human applications. However, researchers are confident that by delivering this edema toxin to the brain via the spinal cord, known as intrathecal administration, it will avoid potential toxicity issues in the rest of the body. Nevertheless, it is clear that further investigation is needed to better understand any broader impacts that this toxin may have directly on the brain.
So far, initial signs suggest that the activity of this toxin in the brain is highly targeted, with no indications in animal trials showing disruption to other mechanisms such as motor function. The researchers propose an intriguing hypothesis that this remarkable specificity of toxin activity in the brain may be an evolutionary adaptation that helps anthrax bacteria evade detection in the organisms it infects.
The common characteristic of anthrax is black skin lesions, which patients often describe as painless. Researchers speculate that this pain-blocking mechanism could explain the strange phenomenon of pain relief. This study exemplifies how the natural world can assist scientists in developing new methods for pain treatment.
The research has been published in the journal Nature Neuroscience.
