Dual Sensory Innervation of Pulmonary Neuroepithelial Bodies (original) (raw)
The Journal of Physiology, 2008
Lung vagal sensory fibres are broadly categorized as C fibres (nociceptors) and A fibres (non-nociceptive; rapidly and slowly adapting low-threshold stretch receptors). These afferent fibre types differ in degree of myelination, conduction velocity, neuropeptide content, sensitivity to chemical and mechanical stimuli, as well as evoked reflex responses. Recent studies in nociceptive fibres of the somatosensory system indicated that the tetrodotoxin-resistant (TTX-R) voltage-gated sodium channels (VGSC) are preferentially expressed in the nociceptive fibres of the somatosensory system (dorsal root ganglia). Whereas TTX-R sodium currents have been documented in lung vagal sensory nerves fibres, a rigorous comparison of their expression in nociceptive versus non-nociceptive vagal sensory neurons has not been carried out. Using multiple approaches including patch clamp electrophysiology, immunohistochemistry, and single-cell gene expression analysis in the guinea pig, we obtained data supporting the hypothesis that the TTX-R sodium currents are similarly distributed between nodose ganglion A-fibres and C-fibres innervating the lung. Moreover, mRNA and immunoreactivity for the TTX-R VGSC molecules Na V 1.8 and Na V 1.9 were present in nearly all neurons. We conclude that contrary to findings in the somatosensory neurons, TTX-R VGSCs are not preferentially expressed in the nociceptive C-fibre population innervating the lungs.
Afferent nerve endings in the tracheal muscle of guinea-pigs and rats
Anatomy and Embryology, 1991
The trachea of guinea-pigs was stained as a whole-mount preparation with the zinc iodide-osmium technique. A distinct class of nerve endings was observed associated with the tracheal muscle. The endings, issued from myelinated fibres of the vagus nerve via the recurrent laryngeal nerve, are distributed on either side of the midline and ventral to the tips of cartilages. They are interpreted as afferent nerve endings that may correspond to slow adapting stretch receptors identified by physiological studies. Each nerve contributes predominantly, but not exclusively, to the receptors of the ipsilateral side. There are 120–180 receptors along the full length of the guinea-pig trachea, their density being higher at the cranial end. The receptors are variable in size and structural complexity, and, to some extent, also in spatial orientation, but distinct subtypes are not recognizable. Receptors of similar morphology and distribution are found also in the rat trachea. The receptors can also be visualized with a cytochrome oxidase method for nerve endings, but they do not stain with immunohistochemistry for the neuropeptides substance P, calcitonin gene-related peptide, vasointestinal polypeptide and neurotensin.
The Journal of Physiology, 1993
We studied the characteristics of pulmonary sensory receptors whose afferent fibres are in the left vagus nerve of opened-chest rats. The activity of these receptors was recorded during mechanical ventilation approximating eupnoea, as well as during deflation, stepwise inflations and constant-pressure inflations of the lungs. Data were also collected from closed-chest rats and analysed separately. 2. Ninety-four per cent of receptors were located in the ipsilateral lung or airways with the remainder in the contralateral lung. 3. Not only were slowly adapting receptors (SARs) the most abundant pulmonary receptors but 21 % of them were either exclusively or predominantly active during the deflationary phase of the ventilatory cycle. Deflationary units were found in openedand closed-chest rats. The average conduction velocity for all fibres innervating SARs averaged 29-7 m s-'. 4. We found rapidly adapting receptors (RARs) to be extremely rare in the rat. Their activity was sparse and irregular. The conduction velocities of fibres innervating RARs averaged 12 3 m s-'. 5. Far more abundant than RARs in the remaining population of pulmonary fibres were C fibres. They were observed to have an average conduction velocity of 2-1 m s-1, base-level activity which was irregular and a high pressure threshold of activation and were stimulated by intravenous capsaicin injection. 6. Notable differences exist between pulmonary receptors in rats and those reported in other species. The variations include the abundant existence of intrapulmonary SARs with exclusively deflationary modulation and the rarity of RARs. We also encountered C fibres which have not previously been described systematically in the rat.
The Journal of Comparative Neurology, 1991
This study examined the possibility that vasoactive intestinal peptide (VIP)-and substance P (SP)-containing nerve fibers in bronchial smooth muscle, glands, epithelium, and blood vessels originate from neurons of airway ganglia. Explants of airway walls were maintained in culture with the expectation that nerve fibers from neurons of airway ganglia would remain viable, whereas fibers originating from neurons not present in the airway walls would degenerate. Airways were dissected and placed into culture dishes containing CMRL 1066 medium for 3,5, and 7 days. In controls (noncultured), VIP-and SP-like immunoreactivity was observed in nerve fibers associated with bronchial smooth muscle, glands, and blood vessel walls and in nerve cell bodies of airway ganglia. Nerve fibers containing SP were also observed within the bronchial epithelium. After 3,5, and 7 days in culture, VIP-and SP-containing fibers were identified in all of the same locations except in the airway epithelium where SP-containing fibers could not be demonstrated. VIP and SP were frequently colocalized in the same nerve fibers of bronchial smooth muscle and glands in controls and cultured airways. There were no statistically significant differences in nerve fiber density for either VIPor SP-containing fibers in bronchial smooth muscle between controlled and cultured airways. VIP concentrations in cultured airways were significantly less than in controls. The results suggest that a large proportion of VIP-and SP-containing nerve fibers supplying bronchial smooth muscle, glands, and blood vessels in the airways originate from neurons of airway ganglia.
Vagal nerve endings in visceral pleura and triangular ligaments of the rat lung
Journal of Anatomy, 2016
The inner thoracic cavity is lined by the parietal pleura, and the lung lobes are covered by the visceral pleura. The parietal and visceral plurae form the pleural cavity that has negative pressure within to enable normal respiration. The lung tissues are bilaterally innervated by vagal and spinal nerves, including sensory and motor components. This complicated innervation pattern has made it difficult to discern the vagal vs. spinal processes in the pulmonary visceral pleura. With and without vagotomy, we identified vagal nerve fibres and endings distributed extensively in the visceral pleura ('P'-type nerve endings) and triangular ligaments ('L'-type nerve endings) by injecting wheat germ agglutinin-horseradish peroxidase as a tracer into the nucleus of solitary tract or nodose ganglion of male Sprague-Dawley rats. We found the hilar and non-hilar vagal pulmonary pleural innervation pathways. In the hilar pathway, vagal sub-branches enter the hilum and follow the pleural sheet to give off the terminal arborizations. In the non-hilar pathway, vagal sub-branches run caudally along the oesophagus and either directly enter the ventral-middle-mediastinal left lobe or follow the triangular ligaments to enter the left and inferior lobe. Both vagi innervate: (i) the superior, middle and accessory lobes on the ventral surfaces that face the heart; (ii) the dorsal-rostral superior lobe; (iii) the dorsal-caudal left lobe; and (iv) the left triangular ligament. Innervated only by the left vagus is: (i) the ventral-rostral and dorsal-rostral left lobe via the hilar pathway; (ii) the ventral-middle-mediastinal left lobe and the dorsal accessory lobe that face the left lobe via the non-hilar pathway; and (iii) the ventral-rostral inferior lobe that faces the heart. Innervated only by the right vagus, via the non-hilar pathway, is: (i) the inferior (ventral and dorsal) and left (ventral only) lobe in the area near the triangular ligament; (ii) the dorsal-middle-mediastinal left lobe; and (iii) the right triangular ligament. Other regions innervated with unknown vagal pathways include: (i) the middle lobe that faces the superior and inferior lobe; (ii) the rostral-mediastinal inferior lobe that faces the middle lobe; and (iii) the ventral accessory lobe that faces the diaphragm. Our study demonstrated that most areas that face the dorsal thoracic cavity have no vagal innervation, whereas the interlobar and heart-facing areas are bilaterally or unilaterally innervated with a left-rostral vs. right-caudal lateralized innervation pattern. This innervation pattern may account for the fact that the respiratory regulation in rats has a lateralized right-side dominant pattern.
Innervation of lower airways and neuropeptide effects on bronchial and vascular tone in the pig
Cell and Tissue Research, 1990
The occurrence and distribution of peptidecontaining nerve fibres [substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), neuropeptide Y (NPY)] and noradrenergic nerve fibres [tyrosine hydroxylase (TH)-and dopamine beta hydroxylase (DBH)-positive] in the airways of the pig were studied by means of immunohistochemistry. SP-and CGRPimmunoreactive (-IR) nerve fibres were present close to and within the lining respiratory epithelium, around blood vessels, within the tracheobronchial smooth muscle layer and around local tracheobronchial ganglion cells. The content of CGRP-and neurokinin A (NKA)like immunoreactivity (-LI) measured by radioimmunoassay (RIA) was twice as high in the trachea compared to that in the peripheral bronchi. SP was a more potent constrictor agent than NKA on pig bronchi in vitro. CGRP had a relaxant effect on precontracted pig bronchi. On blood vessels CGRP exerted a relaxant effect that was more pronounced on pulmonary arteries than on bronchial arteries. VIP/PHI-IR fibres were seen in association with exocrine glands and in the tracheobronchial smooth muscle layer. VIP-positive nerve fibres were abundant around blood vessels in the trachea but sparse or absent around blood vessels in the peripheral bronchi. This histological finding was supported by RIA; it was shown that the content of peptides displaying VIP-like immunoreactivity (-LI) was 18 times higher in the trachea compared to peripheral bronchi. VIP was equally potent as CGRP in relaxing precontracted pig bronchi in vitro. Both bronchial and pulmonary arteries were relaxed by VIP. NPY was colocalized with VIP in tracheal periglandular nerve fibres and in nerve fibres within the tracheobronchial smooth muscle layer. NPY was also present in noradrenergic (DBH-positive) vascular nerve fibres. The content of NPY was much higher (15-fold) in the trachea compared to small bronchi. NPY caused a contraction of both pulmonary and bronchial Send offprint requests to: Dr. Claes-Roland Martling, Department of Anaesthesia, Karolinska Hospital, Box 60500, S-10401 Stockholm, Sweden arteries. The bronchial smooth muscle contraction to field stimulation in vitro was purely cholinergic. A noncholinergic relaxatory effect following field stimulation was observed after bronchial precontraction. Capsaicin had no effect on pig bronchi in vitro.
Transduction mechanisms in airway sensory nerves
Journal of applied physiology (Bethesda, Md. : 1985), 2006
The induction of action potentials in airway sensory nerves relies on events leading to the opening of cation channels in the nerve terminal membrane and subsequent membrane depolarization. If the membrane depolarization is of sufficient rate and amplitude, action potential initiation will occur. The action potentials are then conducted to the central nervous system, leading to the initiation of various sensations and cardiorespiratory reflexes. Triggering events in airway sensory nerves include mechanical perturbation, inflammatory mediators, pH, temperature, and osmolarity acting through a variety of ionotropic and metabotropic receptors. Action potential initiation can be modulated (positively or negatively) through independent mechanisms caused mainly by autacoids and other metabotropic receptor ligands. Finally, gene expression of sensory nerves can be altered in adult mammals. This neuroplasticity can change the function of sensory nerves and likely involve both neurotrophin a...
Spinal afferent neurons projecting to the rat lung and pleura express acid sensitive channels
Respiratory research, 2006
The acid sensitive ion channels TRPV1 (transient receptor potential vanilloid receptor-1) and ASIC3 (acid sensing ion channel-3) respond to tissue acidification in the range that occurs during painful conditions such as inflammation and ischemia. Here, we investigated to which extent they are expressed by rat dorsal root ganglion neurons projecting to lung and pleura, respectively. The tracer DiI was either injected into the left lung or applied to the costal pleura. Retrogradely labelled dorsal root ganglion neurons were subjected to triple-labelling immunohistochemistry using antisera against TRPV1, ASIC3 and neurofilament 68 (marker for myelinated neurons), and their soma diameter was measured. Whereas 22% of pulmonary spinal afferents contained neither channel-immunoreactivity, at least one is expressed by 97% of pleural afferents. TRPV1+/ASIC3- neurons with probably slow conduction velocity (small soma, neurofilament 68-negative) were significantly more frequent among pleural (...
Pulmonary sensory and reflex responses in the mouse
Journal of Applied Physiology, 2006
Mouse model research is proliferating because of its readiness for genetic manipulation. Little is known about pulmonary vagal afferents in mice, however. The purpose of this study was to determine whether their pulmonary afferents are similar to those in large animals. Single-unit activity was recorded in the cervical vagus nerve of anesthetized, open-chest, and mechanically ventilated mice. We evaluated airway sensory activity in 153 single units; 141 were mechanosensitive, with 134 inflation receptors and 7 deflation receptors. The remaining 12 receptors were chemosensitive and mechanically insensitive, showing low basal firing frequency and behaving like C-fiber or high-threshold Aδ-receptors. In separate studies, phrenic activity was recorded as an index of respiratory drive to assess pulmonary reflexes. Lung inflation produced a typical Hering-Breuer reflex, and intravenous injection of phenylbiguanide produced the typical chemoreflex resulting in apnea, bradycardia, and hypot...
Naunyn-Schmiedeberg's Archives of Pharmacology, 1990
1. In the presence of atropine and guanethidine (3 gmol/1 each), electrical field stimulation (1-20 Hz) produced frequency-dependent relaxations of the histamine-(3 gmol/1) induced vascular tone in isolated rings from the guinea-pig pulmonary artery. The electricallyevoked relaxations were abolished by tetrodotoxin (1 gmol/1). The amplitude of these nerve-mediated, nonadrenergic non-cholinergic (NANC) relaxations was unaffected by removal of the vascular endothelium produced through rubbing of the internal surface. 2. Capsaicin (1 gmol/1) produced a prompt and sustained relaxation of the histamine-induced tone which was unaffected by removal of the endothelium. A second application of capsaicin 60-120 rain later had no further relaxant effect, indicating desensitization. After in vitro capsaicin desensitization, the electrically-evoked NANC relaxations were abolished, both in the presence or absence of the vascular endothelium. 3. Substance P evoked a prompt and transient relaxation in precontracted arterial rings with intact endothelium and a transient small contraction in rings in which the endothelium had been mechanically removed. The selective NK-I receptor agonist, [Pro9]-substance P sulfone closely mimicked the relaxation produced by substance P while the selective NK-2 or NK-3 receptor agonists had no relaxant effect. Tachyphylaxis to substance P did not modify the amplitude of the capsaicin-induced relaxation. 4. Human alpha calcitonin gene-related peptide (CGRP) produced a prompt and sustained relaxation both in the presence and absence of the vascular endothelium. 5. Ruthenium red (10 gmol/1) blocked the relaxation to capsaicin while leaving unaffected the relaxation to electrical field stimulation or CGRP (0.1 gmol/1). 6. Both substance P (SP)and CGRP-like immunoreactivities (LI) were detected in extracts of the guinea-pig pulmonary artery. Capsaicin (1 gmol/1) evoked a prompt and simultaneous outflow of both SP-and CGRP-LI. A second application of capsaicin 60 rain later failed to increase SP-or CGRP-LI out-Send offprint requests to C. A. Maggi at the above address flow, indicating complete desensitization. A small but clearly detectable release of both SP-LI and CGRP-LI was also evoked by electrical field stimulation. 7. These findings provide evidence that the neurogenic NANC vasodilation in the guinea-pig pulmonary artery is due to antidromic activation of peripheral endings of capsaicinsensitive primary afferents. Endogenous CGRP is a likely mediator for this vasodilation. No evidence was found that endogenous SP might contribute to vasodilation by activating NK-I receptors on endothelial cells.