Distribution of transient receptor potential cation channel subfamily V member 1-expressing nerve fibers in mouse esophagus

Abstract

Transient receptor potential cation channel subfamily V member 1 (TRPV1) plays a role in esophageal function. However, the distribution of TRPV1 nerve fibers in the esophagus is currently not well understood. In the present study, we investigated the distribution of TRPV1 and neurotransmitters released from TRPV1 nerve fibers in the mouse lower esophagus. Furthermore, we investigated changes in the presence of TRPV1 in the mouse model of esophagitis. Numerous TRPV1-immunoreactive nerve fibers were seen in both the submucosal layer and myenteric plexus of the lower esophagus and colocalized with calcitonin gene-related peptide (CGRP). TRPV1 colocalized with substance P in axons in the submucosal layer and myenteric plexus. TRPV1 colocalized with neuronal nitric oxide synthase in the myenteric plexus. We observed some colocalization of CGRP with the vesicular acetylcholine (ACh) transporter, packaging of ACh into synaptic vesicles after its synthesis in terminal cytoplasm, in the submucosal layer and myenteric plexus. In the esophagitis model, the number of the TRPV1 nerve fibers did not change, but their immunoreactive intensity increased compared with sham-operated mice. Inhibitory effect of exogenous capsaicin on electrically stimulated twitch contraction significantly increased in esophagitis model compared with the effect in sham-operated mice. Overall, these results suggest that TRPV1 nerve fibers projecting to both the submucosal and muscle layer of the esophagus are extrinsic spinal and vagal afferent neurons. Furthermore, TRPV1 nerve fibers contain CGRP, substance P, nitric oxide, and ACh. Therefore, acid influx-mediated TRPV1 activation may play a role in regulating esophageal relaxation.

Capsaicin, Nociception and Pain

“…In keeping with this observation, TRPV1 KO mice develop a significantly less severe esophagitis after acid exposure [154]. Moreover, capsaicin causes enhanced relaxation of smooth muscle contraction in the esophagitis model, which supports the fact that acid reflux increases the expression of TRPV1 in primary afferent nerves [149]. In TRPV1 deficient mice, reflux promoting surgery induces significantly less mucosal injury and inflammation than in WT mice and pretreatment with the TRPV1 antagonist capsazepine in WT mice significantly inhibits esophagitis [152].…”

“…TRPV1-IR nerve fibers deriving from these neurons are found in both the submucosal and myenteric plexuses of the esophagus. These fibers also express CGRP/substance P and neuronal nitric oxide synthase (nNOS) in the myenteric plexus of mice [149], and can be activated by capsaicin [150]. After exposure of the rat esophagus to acids, TRPV1 increases in DRGs [148,151].…”

Role of TRPV1 receptor in inflammation and impairment of esophageal mucosal integrity in a murine model of nonerosive reflux disease

“…It has been suggested that TRPV1 receptors are expressed in afferent neuronal fibers, as observed in biopsies of patients with NERD, and in non‐neuronal cells, such as esophageal epithelial cells . A recent study demonstrated CGRP‐positive nerves close to the esophageal lumen in patients with NERD, which colocalized with TRPV1‐immunoreactive nerve fibers in mouse esophagus . Thus, further investigations are necessary.…”

“…8,26 A recent study demonstrated CGRP-positive nerves close to the esophageal lumen in patients with NERD, 27 which colocalized with TRPV1-immunoreactive nerve fibers in mouse esophagus. 28 Thus, further investigations are necessary.…”

Exploration of the Esophageal Mucosal Barrier in Non-Erosive Reflux Disease

“…Furthermore, the mucosal TRPV1 mRNA in our study is most likely to originate from non-neural cells (such as epithelial cells), as under normal conditions, there is no translation of TRPV1 in peripheral nerve terminals [43,44]. The expression of the TRPV1 protein on peripheral nerve endings, however, might be altered and more research using immunohistochemistry or Western blot analysis to determine the TRPV1 protein expression is warranted.…”