Injury receptors are a type of sensory neuron that alerts us to potentially harmful environmental changes or stimuli, such as extreme heat or stress. Their messages are converted into pain feelings in the brain. Specific forms of pathogenic bacteria can also be detected by injury receptors, either directly or through toxins produced by bacteria. Some bacteria, however, secrete chemicals that suppress pain signals in order to avoid host detection.
Acute and chronic pains have long plagued many adults. The lack of a valid objective basis for the diagnosis of pain has led to the current proliferation of opioid pain medications due to the extraordinary complexity of the brain's mechanisms for regulating pain. Although opioids are the most effective pain medications available, they have serious side effects—they are highly addictive due to their ability to reshape the brain's reward system and to inhibit breathing, which can be life-threatening.
Therefore, there is a very large and urgent clinical need to develop non-opioid pain medications that are non-addictive and effective.
On December 20, 2021, Isaac Chiu et al. of Harvard Medical School published a research paper in Nature Neuroscience titled "Anthrax toxins regulate pain signaling and can deliver molecular cargoes into ANTXR2+ DRG sensory neurons". The study shows that the dreaded deadly bacterium Bacillus anthracis has an unexpected benefit that its release of anthrax toxin relieves a wide range of pain in animals, suggesting that anthrax toxin may serve as a new potential analgesic therapy.
Bacillus anthracis (B. anthracis) is a highly contagious bacterium that is exceedingly deadly. Human infection causes skin necrosis, ulceration, scabbing, and extensive edema of surrounding tissues, as well as toxemia symptoms and, in rare cases, sepsis of the lungs, intestines, and meninges. As B. anthracis can form spore structures, it can survive for a long period in nature.
Isaac Chiu et al. discovered that the receptors expressed by dorsal root ganglion cells—a specific sensory neuron in the paraspinal cord of mouse and human, bind to anthrax toxin. Furthermore, mice treated with edema toxin, an anthrax toxin, were less sensitive to painful stimuli such as heat or needling. This effect is dependent on sensory neurons that express anthrax receptors. Edema toxin was found to disrupt signaling between sensory neurons in rat and human stem cell cultures, albeit the exact method by which it lowers pain signaling is unknown.
Furthermore, these findings raise another intriguing question: why do bacteria decrease pain from an evolutionary standpoint?
According to Isaac Chiu, one plausible explanation is that microorganisms have evolved ways to communicate with their hosts in order to assist their own propagation and survival. They hinder the host from feeling the presence of a bacterial infection by limiting the host's ability to perceive pain in the instance of B. anthracis.
This understanding of the interaction between anthrax toxin derivatives and pain receptors could facilitate the development of new research tools and analgesic medication improvements.
Finally, the researchers stressed that the study is preliminary and that it must be examined in more animal studies to ensure its safety before it can eventually be studied in human.