TRPA1 Integrates Nociceptive and Immune Signaling in Hydra vulgaris

Transient receptor potential ankyrin 1 (TRPA1) channels detect noxious cold and inflammatory mediators in mammals; yet their evolutionary origins and roles in neuro-immune integration remain unclear. Here, we investigated TRPA1 in Hydra vulgaris, an early metazoan with a simple nervous system, exposing polyps to noxious cold and Pseudomonas aeruginosa lysate. Using Western blotting, pharmacological modulation, and gene expression analyses, we demonstrated that TRPA1 mediates upregulation of nociceptive markers (Nrf2, NOS, SOD) and immune effectors (NF-κB, NOS, periculin, hydramacin). TRPA1 antagonism significantly reduced these responses, indicating its role as an amplifier of both nociceptive and innate immune signaling. These findings suggest that TRPA1-dependent coupling of nociceptive-like and immune responses is an ancient, conserved mechanism, providing insights into the molecular basis of integrated threat detection and offering potential avenues for targeting pain and inflammation-associated pathologies.