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

Abstract

Leishmaniases are neglected diseases causing significant deaths and disabilities. In Brazil, the most prevalent form is cutaneous leishmaniasis, characterized by painless lesions despite intense inflammation and ulceration. While BALB/c mice models exhibit hypersensitization to inflammatory stimuli, C57BL/6 mice better mimic human-like lesion progression and nociceptive responses. This study aimed to investigate the mechanisms underlying nociceptive changes in cutaneous leishmaniasis using the C57BL/6 model. Following infection with L. amazonensis, behavioral and nociceptive tests revealed unaltered mechanical nociception and motor capacity, though thermal hypersensitivity emerged during the chronic phase. Elevated IL-1{beta} production in the lesions and upregulation of TRPV1 in dorsal root ganglia (DRG) neurons were detected via ELISA and qPCR. Mice deficient in IL-1{beta}-related proteins or receptors exhibited higher thermal nociception thresholds, highlighting IL-1{beta}s role in heat hypersensitization during late infection stages. Microscopy of chronic lesions revealed tissue deformities, indicating desensitization to mechanical and inflammatory stimuli due to nerve terminal alterations and fibroplasia from regenerative processes. Conversely, thermal hypersensitivity in chronic phases was driven by IL-1{beta} effects on thermal nociceptive neurons in the DRG. These findings suggest that IL-1{beta} and TRPV1 contribute to thermal hypersensitivity, while structural changes in lesions underlie mechanical desensitization. This model provides insights into the complex nociceptive mechanisms of cutaneous leishmaniasis.