Background <p>The nervous system senses microbial signals to influence host defense. Pain-sensing nociceptor neurons are key regulators of the host response to infection, but how they perceive infections is not well understood. Using <i>Caenorhabditis elegans</i> as a tractable model host that shares many features with mammalian systems, we investigated the effects of infection on nociceptor function in vivo.</p> Results <p>In vivo intracellular Ca²⁺ imaging of <i>C. elegans</i> nociceptor ASH neurons revealed a drastic reduction in ASH responses to aversive stimuli in <i>Staphylococcus aureus</i>-infected animals compared to noninfected controls. Morphological examination revealed that ASH neurons lost integrity in the sensory processes reaching the mouth. Neighboring neurons did not show this pathogen-induced neurite pathology (PaIN) phenotype. During acute pathogen exposure, ASH neurons experience Ca²⁺ suppression. Genetic analysis indicated that apoptosis, necrosis, ferroptosis, and autophagy are not essential for the PaIN phenotype. Conversely, loss of the evolutionarily conserved stress-response transcription factor HLH-30/TFEB decreased the penetrance of ASH PaIN by approximately 50%. Additionally, infected animals exhibited defective ASH-mediated evasive behaviors, suggesting that the <i>S. aureus</i>-triggered reduction in ASH activation and morphological degeneration is physiologically relevant.</p> Conclusions <p><i>S. aureus</i> damages nociceptor integrity in <i>C. elegans</i>: ASH neurons experience acute Ca²⁺ suppression—most pronounced with stationary-phase cultures—and extended exposure leads to structural damage and decreased avoidance behavior. This connection between pathogen physiology and circuit failure suggests that infection-evoked nociceptor PaIN may contribute to sensory dysfunction, highlighting the need to identify the responsible bacterial factor(s) and their host targets.</p>