Learning About Pain from a Master Manipulator
Leishmania parasites often cause puzzlingly painless lesions. Scientists are beginning to dig into the mechanisms underlying this pain-blocking effect.
Hannah joined The Scientist as an assistant editor in 2023. She earned her PhD in neuroscience from the University of Washington in 2017 and completed the Dalla Lana Fellowship in Global Journalism in 2020.
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For decades, researchers around the world have been investigating the molecular mechanisms by which microbes cause pain. Abhay Satoskar, a parasite immunology researcher at Ohio State University, is interested in the opposite question: How can a microbe relieve pain?
More specifically, Satoskar wants to explore the relationship between mammalian hosts and Leishmania mexicana, a unicellular parasite that causes chronic but surprisingly painless skin lesions. In a study published in iScience, Satoskar and his colleagues identified changes in host cell metabolism that may underlie these analgesic effects.1
“It is fascinating to learn how this bug is evading host detection by manipulating not only the immune system, but in this case, even the sensory system,” said Satoskar.
By using mass spectrometry, his team measured differences in metabolites between infected and noninfected tissues in a mouse model of the disease. They found that L. mexicana infection altered purine metabolism at the lesion site; some of the upregulated purine metabolites, including xanthine, hypoxanthine, and inosine, are thought to play relevant roles in anti-nociception. Researchers also identified enrichment of certain pain-numbing endocannabinoid metabolites.
“There is still a lot to explain,” said Ricardo Silvestre, an immunometabolism researcher at the University of Minho who was not involved in the study. “The work was mainly descriptive, and they are very honest in the paper about the limitations of the study. [However], I believe it opens a new field of research that many will follow.”
One major limitation—the use of a mouse model—Satoskar hopes to remedy soon by validating these findings in human L. mexicana lesions. He also wants to dig deeper into the mechanisms governing infection-related shifts in these metabolic pathways, and noted that elucidating how L. mexicana manipulates nociception could have far-reaching effects. “If we find the mechanism—let's say a parasite molecule—it could be an important pain killer that could be used for other diseases,” said Satoskar.
- Volpedo G et al. iScience. 2023;26(12):108502.
