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, Drosophila melanogaster 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. • We address conflicting findings in capsaicin perception in fruit flies, examining inconsistencies in the literature regarding the presence or absence of capsaicin sensation. • The absence of a TRPV1 ortholog in fruit flies suggests that their response to capsaicin may involve alternative chemosensory mechanisms rather than direct TRPV1-like activation. • If capsaicin sensation exists in Drosophila, it may occur through stimulation of gustatory chemosensory systems or activation of paralogous TRP channels. • If capsaicin sensation is absent, Drosophila may still experience indirect effects from capsaicin exposure through TRPV1-independent mechanisms or capsaicin metabolism.
Flores-Iga et al. (Sat,) studied this question.