Abstract
Transient receptor potential vanilloid type 2 (TRPV2) and type 1 (TRPV1) are originally identified as heat-sensitive TRP channels. We compared the expression patterns of TRPV2 and TRPV1 in the rat distal colon and extrinsic primary afferent neurons, and investigated their roles in visceral hypersensitivity in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis rats. Both TRPV2 and TRPV1 expressions in the colon, dorsal root ganglion (DRG), and nodose ganglion (NG) were significantly upregulated in the TNBS-induced colitis model. TRPV2 cell bodies co-localized with the intrinsic primary afferent marker NeuN and the inhibitory motor neuronal marker nNOS in the myenteric plexus. TRPV2 expressions were further detected in the resident macrophage marker ED2 in the mucosa. In contrast, no TRPV1-expressing cell bodies were detected in the myenteric plexus. Both TRPV2- and TRPV1-positive cell bodies in the DRG and NG were double-labeled with the neuronal retrograde tracer fluorescent fluorogold. Large- and medium-sized TRPV2-positive neurons were labeled with the A-fiber marker NF200, calcitonin gene-related peptide (CGRP), and substance P (SP) in the DRG while small-sized TRPV1-positive neurons were labeled with the C-fiber markers IB4, CGRP, and SP. TRPV2- and TRPV1-positive NG neurons were labeled with NF200 and IB4. TNBS treatment increased p-ERK1/2-positive cells in TRPV2 and TRPV1 neurons but did not affect the TRPV2 and TRPV1 subpopulations in the DRG and NG. Both TRPV2 and TRPV1 antagonists significantly alleviated visceral hypersensitivity in TNBS-induced colitis model rats. These findings suggest that intrinsic/extrinsic TRPV2- and extrinsic TRPV1-neurons contribute to visceral hypersensitivity in an experimental colitis model.
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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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This work was supported in part by the Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (#19K07109 and #22K06656 to Kenjiro Matsumoto).
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KM, SH, and SK planned and designed the experiments. FS, TM, TH, RO, and TN performed the experiments. KM, FS, TM, and SK analyzed the data. KM, and SK wrote the manuscript. KM, HY, MAK, and SK reviewed and discussed the data. All authors read and approved the final manuscript.
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All experiments involving animals were performed in accordance with the ARRIVE guidelines (McGrath and Lilley 2015). The protocols were approved by the Committee on the Ethics of Animal Research of Kyoto Pharmaceutical University, Japan (permit number: 18–019).
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Matsumoto, K., Sugimoto, F., Mizuno, T. et al. Immunohistochemical characterization of transient receptor potential vanilloid types 2 and 1 in a trinitrobenzene sulfonic acid-induced rat colitis model with visceral hypersensitivity. Cell Tissue Res 391, 287–303 (2023). https://doi.org/10.1007/s00441-022-03723-9
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DOI: https://doi.org/10.1007/s00441-022-03723-9