Spinal afferent neurons projecting to the rat lung and pleura express acid sensitive channels

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (35%) than pulmonary afferents (20%). TRPV1(+)/ASIC3(+ )neurons amounted to 14 and 10% respectively. TRPV1(-)/ASIC3(+ )neurons made up between 44% (lung) and 48% (pleura) of neurons, and half of them presumably conducted in the A-fibre range (larger soma, neurofilament 68-positive). CONCLUSION: Rat pleural and pulmonary spinal afferents express at least two different acid-sensitive channels that make them suitable to monitor tissue acidification. Patterns of co-expression and structural markers define neuronal subgroups that can be inferred to subserve different functions and may initiate specific reflex responses. The higher prevalence of TRPV1(+)/ASIC3(- )neurons among pleural afferents probably reflects the high sensitivity of the parietal pleura to painful stimuli

Endothelin-1 as a neuropeptide: neurotransmitter or neurovascular effects?

Endothelin-1 (ET-1) is an endothelium-derived peptide that also possesses potent mitogenic activity. There is also a suggestion the ET-1 is a neuropeptide, based mainly on its histological identification in both the central and peripheral nervous system in a number of species, including man. A neuropeptide role for ET-1 is supported by studies showing a variety of effects caused following its administration into different regions of the brain and by application to peripheral nerves. In addition there are studies proposing that ET-1 is implicated in a number of neural circuits where its transmitter affects range from a role in pain and temperature control to its action on the hypothalamo-neurosecretory system. While the effect of ET-1 on nerve tissue is beyond doubt, its action on nerve blood flow is often ignored. Here, we review data generated in a number of species and using a variety of experimental models. Studies range from those showing the distribution of ET-1 and its receptors in nerve tissue to those describing numerous neurally-mediated effects of ET-1

The Contribution of the Left Phrenic Nerve to Innervation of the Esophagogastric Junction

The contribution of the left phrenic nerve to innervation of the esophagogastric junction. The esophagogastric junction is part of the barrier preventing gastroesophageal reflux. We have investigated the contribution of the phrenic nerves to innervation of the esophagogastric junction in humans and piglets by dissecting 30 embalmed human specimens and 14 piglets. Samples were microdissected and nerves were stained and examined by light and electron microscopy. In 76.6% of the human specimens, the left phrenic nerve participated in the innervation of the esophagogastric junction by forming a neural network together with the celiac plexus (46.6%) or by sending off a distinct phrenic branch, which joined the anterior vagal trunk (20%). Distinct left phrenic branches were always accompanied by small branches of the left inferior phrenic artery. In 10% there were indirect connections with a distinct phrenic nerve branch joining the celiac ganglion, from which celiac plexus branches to the esophagogastric junction emerged. Morphological examination of phrenic branches revealed strong similarities to autonomic celiac plexus branches. There was no contribution of the left phrenic nerve or accompanying arteries from the caudal phrenic artery in any of the piglets. The right phrenic nerve made no contribution in any of the human or piglet samples. We conclude that the left phrenic nerve in humans contributes to the innervation of the esophagogastric junction by providing ancillary autonomic nerve fibers. Experimental studies of the innervation in pigs should consider that neither of the phrenic nerves was found to contribute. Clin. Anat., 2019