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Background: Previous studies suggest that transient receptor potential (TRP) channels and neurogenic inflammation may be involved in idiopathic pulmonary fibrosis (IPF)-related high cough sensitivity, although the details of mechanism are largely unknown. Here, we aimed to further explore the potential mechanism involved in IPF-related high cough sensitivity to capsaicin challenge in a guinea pig model of pulmonary fibrosis induced by bleomycin.Methods: Western blotting and real-time quantitative polymerase chain reaction (RT-qPCR) were employed to measure the expression of TRP channel subfamily A, member 1 (TRPA1) and TRP vanilloid 1 (TRPV1), which may be involved in the cough reflex pathway. Immunohistochemical analysis and RT-qPCR were used to detect the expression of neuropeptides substance P (SP), Neurokinin-1 receptor (NK1R), and calcitonin gene-related peptide (CGRP) in lung tissues. Concentrations of nerve growth factor (NGF), SP, neurokinin A (NKA), neurokinin B (NKB), and brain-derived neurotrophic factor (BDNF) in lung tissue homogenates were measured by ELISA.Results: Cough sensitivity to capsaicin was significantly higher in the model group than that of the sham group. RT-qPCR and immunohistochemical analysis showed that the expression of TRPA1 and TRPV1 in the jugular ganglion and nodal ganglion, and SP, NK1R, and CGRP in lung tissue was significantly higher in the model group than the control group. In addition, expression of TRP and neurogenic factors was positively correlated with cough sensitivity of the experimental animals.Conclusion: Up-regulated expression of TRPA1 and TRPV1 in the cough reflex pathway and neurogenic inflammation might contribute to the IPF-related high cough sensitivity in guinea pig model. [ABSTRACT FROM AUTHOR]

Abstract: We have determined the localization of calcitonin gene-related peptide-immunoreactive (CGRP-ir) and calretinin-ir neurons in the vagal ganglia that innervate the cervical or subdiaphragmatic esophagus. Many CGRP-ir neurons were found exclusively in the jugular ganglion located in the cranial cavity. Calretinin-ir neurons were distributed throughout the vagal ganglia. Injection of Fluorogold into the cervical esophagus resulted in many Fluorogold-labeled neurons in the jugular and nodose ganglia. Injection of Fluorogold into the subdiaphragmatic esophagus resulted in many Fluorogold-labeled neurons, with most in the nodose ganglion. In the case of Fluorogold injection into the cervical esophagus, double-labeling combining immunohistochemistry and retrograde tracing showed that about 40% of the Fluorogold-labeled neurons in the jugular ganglion express CGRP-like immunoreactivity, and about 20% of the Fluorogold-labeled neurons in both the jugular and nodose ganglia express calretinin-like immunoreactivity. In the case of injection into the subdiaphragmatic esophagus, only a few Fluorogold-labeled neurons express CGRP-like immunoreactivity or calretinin-like immunoreactivity in the vagal ganglia. These results indicate that the cervical esophagus receives projections from many CGRP-ir neurons in the jugular ganglion and from calretinin-ir neurons in the jugular and nodose ganglia, while the subdiaphragmatic esophagus receives projections from only a few CGRP-ir and calretinin-ir neurons in the vagal ganglia. [Copyright &y& Elsevier]

Abstract: We have studied the connections of calcitonin gene-related peptide immunoreactive (CGRP-ir) sensory neurons in the ganglia of the vagus nerve. Many CGRP-ir neurons were identified in the jugular ganglion located in the cranial cavity, while fewer CGRP-ir neurons were found in the nodose ganglion located at the level of the jugular foramen. Application of Fluorogold to the cut end of the cervical vagus nerve resulted in many Fluorogold-labeled neurons in both the jugular and the nodose ganglia. Application of Fluorogold to the cut end of the subdiaphragmatic vagus nerve resulted in Fluorogold-labeled neurons mostly in the nodose ganglion with only a few labeled neurons in the jugular ganglion. Injection of Fluorogold into the heart resulted in Fluorogold-labeled neurons in both the jugular and the nodose ganglia. Double labeling combining CGRP immunohistochemistry and Fluorogold retrograde tracing showed that in cases of both the application of Fluorogold to the cut end of the cervical vagus nerve and the injection of Fluorogold into the heart, about 40% of the Fluorogold-labeled neurons in the jugular ganglion expressed CGRP-like immunoreactivity. These results indicate that many CGRP-ir neurons in the jugular ganglion innervate the cervical and thoracic visceral organs, including the heart, but only a few CGRP-ir neurons project to the abdominal visceral organs. [Copyright &y& Elsevier]

Abstract: Immunohistochemistry for delta-opioid receptor (DOR) was performed on the rat cranial sensory ganglia. The immunoreactivity was detected in 16%, 19% and 11% of neurons in the trigeminal, jugular and petrosal ganglia, respectively. The nodose ganglion was devoid of such neurons. DOR-immunoreactive (IR) neurons were mostly small to medium-sized (trigeminal, range = 62–851 μm2, mean ± SD = 359 ± 175 μm2; jugular, range = 120–854 μm2, mean ± SD = 409 ± 196 μm2; petrosal, range = 167–1146 μm2, mean ± SD = 423 ± 233 μm2). Double immunofluorescence method revealed that all DOR-IR neurons were also immunoreactive for calcitonin gene-related peptide. The cutaneous and mucosal epithelia in the oro-facial region, tooth pulp, taste bud and carotid body were innervated by DOR-IR nerve fibers. In the brainstem, IR nerve terminals were located in the superficial medullary dorsal horn and dorsomedial part of the subnucleus oralis as well as the solitary tract nucleus. The present study suggests that DOR-IR neurons may be associated with nociceptive and/or chemoreceptive function in the cranial sensory ganglia. [Copyright &y& Elsevier]

• Human jugular ganglion had sensory neurons with small to medium-sized cell bodies. • These neurons contained TRPV1, TRPV2, SP, CGRP and VGLUT2. • Free nerve endings contained the TRPVs and neuropeptides in external auditory canal. • TRPV- and neuropeptide-containing vagal nociceptors probably innervate the periphery. The jugular ganglion (JG) contains sensory neurons of the vagus nerve which innervate somatic and visceral structures in cranial and cervical regions. In this study, the number of sensory neurons in the human JG was investigated. And, the morphology of sensory neurons in the human JG and nodose ganglion (NG) was compared. The estimated number of JG neurons was 2721.8–9301.1 (average number of sensory neurons ± S.D. = 7975.1 ± 3312.8). There was no significant difference in sizes of the neuronal cell body and nucleus within the JG (cell body, 1128.8 ± 99.7 μ m2; nucleus, 127.7 ± 20.8 μ m2) and NG (cell body, 963.8 ± 225.7 μ m2; nucleus, 123.2 ± 32.3 μ m2). These findings indicate that most of sensory neurons show the similar morphology in the JG and NG. Our immunohistochemical method also demonstrated the distribution of ion channels, neurotransmitter agents and calcium-binding proteins in the human JG. Numerous JG neurons were immunoreactive for transient receptor potential cation channel subfamily V member 1 (TRPV1, mean ± SD = 19.9 ± 11.5 %) and calcitonin gene-related peptide (CGRP, 28.4 ± 6.7 %). A moderate number of JG neurons contained TRPV2 (12.0 ± 4.7 %), substance P (SP, 15.7 ± 6.9 %) and secreted protein, acidic and rich in cysteine-like 1 (SPARCL1, 14.6 ± 7.4 %). A few JG neurons had vesicular glutamate transporter 2 (VGLUT2, 5.6 ± 2.9 %) and parvalbumin (PV, 2.3 ± 1.4 %). SP- and TRPV2-containing JG neurons had mainly small and medium-sized cell bodies, respectively. TRPV1- and VGLUT2- containing JG neurons were small to medium-sized. CGRP- and SPARCL1-containing JG neurons were of various cell body sizes. Sensory neurons in the human JG were mostly free of vasoactive intestinal polypeptide (VIP), tyrosine hydroxylase (TH) and neuropeptide Y (NPY). In the external auditory canal skin, subepithelial nerve fibers contained TRPV1, TRPV2, SP, CGRP and VGLUT2. Perivascular nerve fibers also had TRPV1, TRPV2, SP, CGRP, VIP, NPY and TH. However, PV- and SPARCL1-containing nerve endings could not be seen in the external auditory canal. It is likely that sensory neurons in the human JG can transduce nociceptive and mechanoreceptive information from the external auditory canal. Theses neurons may be also associated with neurogenic inflammation in the external auditory canal and ear-cough reflex through the vagus nerve. [ABSTRACT FROM AUTHOR]