Researchers harness the power of a parasite to stop pain

[Dec. 4, 2023: JJ Shavit, The Brighter Side of News]

Cutaneous leishmaniasis, a debilitating parasitic disease affecting millions of people worldwide, has baffled scientists for years due to its unique symptom – painless skin lesions. Recently, researchers from The Ohio State University College of Medicine made a groundbreaking discovery, shedding light on the enigma of painlessness in these lesions. Their findings not only offer a deeper understanding of this disease but also open doors to the development of non-narcotic pain medications.

Cutaneous leishmaniasis, caused by the Leishmania parasite, is known for producing disfiguring skin lesions. However, what has always puzzled scientists is the absence of pain associated with these lesions, especially when compared to the painful blisters caused by other skin conditions like chickenpox, staphylococcus infections, or herpes virus outbreaks.

In a study published in the journal iScience, researchers embarked on a quest to unravel the mystery behind the painless nature of cutaneous leishmaniasis lesions. They conducted experiments on mice by subjecting them to chronic infections with Leishmania mexicana, the species responsible for cutaneous leishmaniasis in the Americas.

Using an unbiased mass spectrometry analysis of the lesions, the scientists identified metabolic signaling pathways that were distinctly altered in infected mice compared to uninfected ones.

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These pathways appeared to be linked to pain suppression, indicating that the Leishmania parasites could manipulate the host's physiological system to dampen pain perception.

Abhay Satoskar, the senior author of the study and a professor of pathology at The Ohio State University College of Medicine, expressed the significance of this discovery, stating, "No one knows why these lesions are painless – but it has been thought that the parasite somehow manipulates the host physiological system." He further added, "Based on our data, something the parasites do triggers pathways that suppress pain. How they do that, we're still investigating."

The research findings raise intriguing questions about the mechanisms employed by the parasites to induce this painlessness. While the exact processes remain a subject of ongoing investigation, the discovery has far-reaching implications.

Beyond advancing our understanding of cutaneous leishmaniasis, this research has the potential to pave the way for the development of non-narcotic pain medications. Satoskar elaborated on this possibility, saying, "We hypothesize that any molecules the parasite's presence is producing could be potential painkillers for other health problems."

To delve deeper into the painlessness mystery, the researchers conducted cell-culture experiments on infected macrophages, immune cells where Leishmania parasites reside. Interestingly, these experiments revealed an increase in many of the same changes observed in the lesions, suggesting a direct or indirect effect of the infection on the cells.

Satoskar acknowledged the complexity of the situation, stating, "The infection does something in the cell that could be a direct or indirect effect – we don't know. But the environment that the infection creates leads to production of these metabolites."

As researchers continue to investigate the cellular basis of painlessness in cutaneous leishmaniasis lesions, they are left with essential questions about the triggers of these pain-suppression pathways. Is it solely the parasite's doing, or is it a result of interactions with the host cell? The answers to these questions could uncover a multitude of intricacies in the relationship between the parasite and the host.

In addition to shedding light on the mysterious painlessness of cutaneous leishmaniasis, Abhay Satoskar and his team have been working on another critical aspect of Leishmania research. They have spearheaded an initiative to develop a standardized skin test for detecting immunity to Leishmania donovani, the parasite responsible for visceral leishmaniasis, a severe form of the disease that affects internal organs and can be fatal if left untreated.

This skin test, which utilizes an antigen called leishmanin, is similar to the skin test used for tuberculosis. A positive response to the test indicates that a person has been exposed to the Leishmania parasite and has cellular immunity to prevent further clinical symptoms. Such a test is crucial for disease surveillance in regions heavily affected by leishmaniasis and will be essential for phase 3 clinical trials of leishmaniasis vaccines developed by the research team.

Satoskar emphasized the importance of this test in the field, explaining, "For many stakeholders going into a community to conduct surveillance, knowing who is immune and who is not immune is essential so they can deploy their limited resources appropriately for disease control."

While leishmanin skin tests have existed in the past, they are no longer available. The research team has taken the initiative to develop this antigen following Good Laboratory Practice guidelines. They tested it in hamsters, a model for human visceral leishmaniasis, to ensure that the skin test triggers the expected immune response to both infection and vaccination.

Satoskar concluded, "This kind of data can be used for fast-track approval for Leishmania vaccines which are under development. We anticipate fulfilling the need of the entire global community."

While the exact mechanisms remain to be elucidated, this research holds promise for not only advancing our understanding of the disease but also for the development of novel pain management strategies. Furthermore, the development of a standardized skin test for Leishmania immunity marks a significant step forward in controlling this devastating disease, potentially benefiting millions of people in endemic regions worldwide.

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.

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