Capsaicin responses in Drosophila: Exploring the possibility of establishing a new Non-TRPV1 model

Capsaicin, the primary pungent compound in chili peppers, activates the heat-sensitive ion channel transient receptor potential vanilloid 1 (TRPV1) in mammals, eliciting the characteristic burning sensation. On the other hand, <i>Drosophila melanogaster</i> is a powerful invertebrate genetic model for linking gene function to behavior and physiology that lacks an ortholog of TRPV1, providing a unique opportunity to uncover how capsaicin affects organisms that do not possess this canonical receptor. Although Drosophila exhibits measurable responses to capsaicin, it remains unclear whether these effects reflect direct sensory detection or indirect metabolic and stress-related processes, as mechanistic evidence remains inconclusive. Here, we synthesize capsaicin-related studies in Drosophila, with a particular emphasis on reconciling opposing findings. We propose emerging conceptual frameworks based on convergent evidence implicating chemosensory pathways, metabolic processes, and physiological responses, and highlight key directions for future research aimed at clarifying the multifaceted interaction of capsaicin in TRPV1-lacking systems.