Transient receptor potential vanilloid (TRPV) channels are found throughout the animal kingdom, where they play an important role in sensory transduction. In this study, we combined physiological studies with in vivo behavioral experiments to examine the presence of a putative TRPV-like receptor in the medicinal leech, building upon earlier studies in this lophotrochozoan invertebrate. The leech polymodal nociceptive neuron was activated by both peripheral and central application of the TRPV1-activator capsaicin in a concentration-dependent manner, with 100 μmol l −1 being the lowest effective concentration. Responses to capsaicin were inhibited by the selective TRPV1 antagonist SB366791. The polymodal nociceptive neuron also responded to noxious thermal stimuli (>40°C), and this response was also blocked by SB366791. Capsaicin sensitivity was selective to the polymodal nociceptor with no direct response being elicited in the mechanical nociceptive neuron or in the nonnociceptive touch-or pressure-sensitive neurons. Capsaicin also elicited nocifensive behavioral responses (withdrawals and locomotion) in a concentration-dependent manner, and these behavioral responses were significantly attenuated with SB366791. These results suggest the presence of a capsaicin-sensitive TRPVlike channel in the medicinal leech central nervous system and are relevant to the evolution of nociceptive signaling. KEY WORDS: Leech, TRPV, Invertebrate, Nociception INTRODUCTIONTransient receptor potential (TRP) channels are a diverse class of non-specific cation channels that are found throughout the animal kingdom (Damann et al., 2008). TRP channels are typically associated with sensory transduction and are often polymodal, such as the mammalian TRP-vanilloid 1 (TRPV1) channel, which responds to noxious thermal (>42°C), mechanical and chemical (low pH, capsaicin) stimuli (Szallasi and Blumberg, 1999). Capsaicin sensitivity varies greatly throughout metazoans, with mammals displaying the greatest response to capsaicin. Birds, once thought to be capsaicin insensitive, have been shown to respond to capsaicin at increased concentrations (30 μmol l −1 ) compared with mammals (Kirifides et al., 2004). Even among mammals, capsaicin sensitivity varies greatly between species, and this variance is further complicated by ontogentic shifts in capsaicin sensitivity within specific strains of mice (Holzer, 1991). Invertebrate sensitivity to capsaicin is no less complicated because ecdysozoans, such as Drosophila (Vriens et al., 2004) and Caenorhabditis elegans (Tobin RESEARCH ARTICLECenter for Brain and Behavior Research, Division of Basic Biomedical Sciences, Sanford, School of Medicine, University of South Dakota, Vermillion, SD 57069, USA. *Author for correspondence (bburrell@usd.edu)Received 23 June 2014; Accepted 7 October 2014 et al., 2002), are reported to be capsaicin insensitive, whereas lophotrochozoans, specifically the gastropod Megalobulimus (KalilGaspar et al., 2007) and the medicinal leech (Hirudo verbana, Carena 1820) (Pasto...