Leishmania amazonensis infection induces IL1β-dependent hyperalgesia, while dampening mechanical allodynia in C57BL/6 mice.

Leishmaniasis is a group of neglected diseases that cause significant mortality and disability. In Brazil, the most prevalent form is cutaneous leishmaniasis, which is characterized by painless lesions despite intense inflammation and ulceration. While BALB/c mouse models exhibit hypersensitivity to inflammatory stimuli, C57BL/6 mice better mimic human-like lesion progression and nociception. This study aimed to investigate the mechanisms underlying nociception in cutaneous leishmaniasis using the C57BL/6 model. Following infection with L. amazonensis, behavioral and nociceptive tests revealed unaltered mechanical nociception and motor capacity, although thermal hyperalgesia was observed during the chronic phase. Elevated IL-1β production in lesions and upregulation of TRPV1 in dorsal root ganglia (DRG) neurons were detected via ELISA and RT-qPCR. Mice deficient in IL-1β signaling components exhibited increased thermal thresholds, highlighting the role of IL-1β in thermal hyperalgesia during chronic infection. Histological analysis of chronic lesions revealed tissue deformities, indicating desensitization to mechanical and inflammatory stimuli due to nerve terminal alterations and fibroplasia resulting from regenerative processes. Conversely, thermal hyperalgesia in the chronic phase is driven by the effects of IL-1β on thermal nociceptive DRG neurons. These findings suggest that IL-1β and TRPV1 contribute to thermal hyperalgesia, whereas structural changes in lesions underlie mechanical desensitization. This model provides insight into the complex nociceptive mechanisms of cutaneous leishmaniasis.