Anthrax conjures thoughts of bioterrorism, though it's a disease caused by a rare but naturally-occurring bacterium, Bacillus anthracis. Scientists have now found that a toxin produced by the infectious pathogen could be a useful pain reliever; researchers determined that it can change the way signals are sent by neurons that sense pain. Reporting in Nature Neuroscience, when the investigators directly treated neurons in an animal model of pain with the toxin, there were signs of pain relief.
At the start of this research, the scientists assessed how neurons that sense pain are different from others, and learned that they carry receptors that can attach to anthrax toxins. Other neurons don't carry those receptors, so the pain receptors were specifically ready to interact with the anthrax toxin.
They researchers found that the anthrax bacterium generates proteins that associate with sensory neurons that send pain signals to the spinal cord, and this association dampens pain sensations. One bacterial protein, called protective antigen (PA), binds to receptors on neurons, which forms a gateway for two other bacterial molecules, edema factor (EF) and lethal factor (LF), and they move into the neuron. PA and EF then function together as 'edema toxin' to change signaling inside the neurons, and silence pain.
When anthrax toxin was injected into the lower spines of mice that had experienced high temperatures or mechanical stimulation that would typically cause pain in untreated animals, the sensation of pain was blocked. The toxin also appeared to relieve pain caused by inflammation or neuronal damage. Otherwise, the mice appeared unaffected; their heart rate, motor coordination, and body temperature was normal, which suggested that the toxin was working in a targeted way. The treated neurons also did not show any signs of damage after the treatment, which indicates that the pain relief did not happen because the cells died or were unable to send signals, but because the pain signals were stopped.
In this study, the researchers also brought portions of the toxin together with other molecules, to engineer treatments that act efficiently on pain-sensing neurons, suggesting it may be possible to design pain therapeutics that are highly effective, but don't involve opioids. One of those molecules was botulinum toxin, another microbial molecule that can be dangerous, but also has therapeutic potential.
While opioids can help relieve pain, they don't work for everyone, and they can change signaling in the brain to cause addiction and dependence.
The anthrax toxin could disrupt the blood brain barrier, so more research will be needed to understand whether this anthrax toxin can help people safely get pain relief, cautioned the researchers, but this study shows it's worth following up on this microbial molecule. The Chiu lab is familiar with other bacterial proteins that can interact with neurons and alter pain signaling, but in this study they set out to identify molecules that might block or diminish pain.
Sources: Harvard Medical School, Nature Neuroscience
