@article{kittaka_debrecht_mishra_2020, title={Differential contribution of sensory transient receptor potential channels in response to the bioactive lipid sphingosine-1-phosphate}, volume={16}, ISSN={["1744-8069"]}, DOI={10.1177/1744806920903515}, abstractNote={Somatosensation encompasses a wide range of sensations including pain, itch, touch, and temperature and is essential for the detection of environmental stimuli, ultimately allowing an organism to escape, communicate, and adapt to its environment. Such sensations are detected by primary sensory neurons whose nerve endings are located in the skin. Compared to external stimuli, mechanisms underlying endogenous stimulation of primary sensory neurons, such as by lipids, are still largely unknown. Here, we focus on one of the endogenous bioactive lipids, sphingosine-1-phosphate (S1P), to investigate the physiological roles of S1P in pain and itch. We showed that S1P-induced calcium responses in sensory neurons through S1P receptors. Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) are nonselective calcium-permeable ion channels that are known to be involved in pain and itch. Neurons that respond to S1P show reduced responsiveness when treated with antagonists that block either TRPA1 or TRPV1 alone or in combination. In addition, using single and double knockout mice (TRPA1; TRPV1; TRPA1/TRPV1) with loss of function of these channels, we demonstrated that both TRP channels are involved in S1P-induced neuronal responses in vitro. Next, we examined the effects of S1P on pain and itch responsiveness in freely behaving mice post-S1P injection into the cheek, neck, and hind paw. Our findings reveal that S1P induces both pain and itch in vivo and that these responses are partially dependent upon the TRPV1, but not TRPA1 channels.}, journal={MOLECULAR PAIN}, author={Kittaka, Hiroki and DeBrecht, Jennifer and Mishra, Santosh K.}, year={2020}, month={Feb} } @article{yamanoi_kittaka_tominaga_2019, title={Cheek Injection Model for Simultaneous Measurement of Pain and Itch-related Behaviors}, ISSN={["1940-087X"]}, DOI={10.3791/58943}, abstractNote={Itch was defined as "an unpleasant cutaneous sensation that provokes a desire to scratch" by Rothman in 1941. In mouse models, scratch bouts are typically counted to evaluate itch induced by pruritogens. However, previous reports have shown that algesic substances also induce scratching behaviors in a mouse neck injection model, which is the most common test used for scratching behaviors. This finding makes it difficult to study itch in mice.  In contrast, capsaicin, a common algogen, reduced scratching behaviors in some neck injection experiments. Therefore, the effect of pain on scratching behaviors remains unclear. It is thus necessary to develop a method to concurrently investigate itch and pain sensation using behavioral tests. Here, a cheek injection model is introduced which can be used to simultaneously measure pain- and itch-related behaviors. In this model, pruritogens induce scratching behaviors while algesic substances induce wiping behaviors. Using this model, lysophosphatidic acid (LPA), an itch mediator found in cholestatic patients with itch, is shown to exclusively induce itch but not pain. However, in mouse models, LPA has been reported to be both a pruritogen and an algogen. Investigation into the effects of LPA in a mouse cheek injection model showed that LPA only induced scratching, but not wiping behaviors. This indicates that LPA acts as a pruritogen similarly in mice and humans, and demonstrates the utility of a cheek injection model for itch research.}, number={151}, journal={JOVE-JOURNAL OF VISUALIZED EXPERIMENTS}, author={Yamanoi, Yu and Kittaka, Hiroki and Tominaga, Makoto}, year={2019}, month={Sep} } @article{panigrahi_praharaj_kittaka_mridha_black_singh_mercer_bokhoven_torkko_agarwal_et al._2019, title={Exosome proteomic analyses identify inflammatory phenotype and novel biomarkers in African American prostate cancer patients}, volume={8}, ISSN={["2045-7634"]}, DOI={10.1002/cam4.1885}, abstractNote={Abstract}, number={3}, journal={CANCER MEDICINE}, author={Panigrahi, Gati K. and Praharaj, Prakash P. and Kittaka, Hiroki and Mridha, Asit R. and Black, Olen M. and Singh, Rakesh and Mercer, Roger and Bokhoven, Adrie and Torkko, Kathleen C. and Agarwal, Chapla and et al.}, year={2019}, month={Mar}, pages={1110–1123} }