Capsaicin-sensitive vagal afferent neurons innervating the rat pancreas

Carobi, C.

doi:10.1016/0304-3940(87)90597-0

Cited by 22 publications

(14 citation statements)

References 14 publications

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“…This suggests that the majority of pancreatic vagal afferents are also unmyelinated or small‐diameter myelinated fibres (Sharkey & Williams, 1983). Similar findings were reported in a study in which the pancreatic vagal innervation was labelled using horseradish peroxidase as a retrograde axonal tracer (Carobi, 1987). Following injection of horseradish peroxidase into the pancreas via the common bile duct, many labelled neurons were detected in the right and left nodose ganglion.…”

Section: The Dmv and Vagovagal Reflexessupporting

confidence: 87%

The dorsal motor nucleus of the vagus and regulation of pancreatic secretory function

Mussa

Verberne

2012

Experimental Physiology

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Section: The Dmv and Vagovagal Reflexessupporting

confidence: 87%

The dorsal motor nucleus of the vagus and regulation of pancreatic secretory function

Mussa

Verberne

2012

Experimental Physiology

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“…Studies of the vagal afferent innervation from the liver (Carobi and Magni 1981;Magni and Carobi 1983;Carobi et al 1985), pancreas (Carobi 1987) and duodenum (Carobi and Candio 1990) of rats by the horseradish peroxidase technique did not reveal a viscerotopic organization in the ganglia, whereas in the cat an electrophysiological investigation of the nodose ganglion has indicated a viscerotopic organization of its sensory neurons (Mei 1970).…”

Section: Introductionmentioning

confidence: 94%

“…Since capsaicin solvent does not seem to have any effect (Jancso et al 1984;Carobi 1987), the data from capsaicin-treated rats have been compared with those of untreated rats, which served as controls. Cell Tissue Res (1996) The other six rats served as untreated controls.…”

Section: Introductionmentioning

confidence: 99%

A quantitative investigation of the effects of neonatal capsaicin treatment on vagal afferent neurons in the rat

Carobi

1996

Cell and Tissue Research

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The sensory cells of the nodose and jugular ganglia of the rat have been quantitatively evaluated in longitudinal paraffin sections. The right vagal ganglia contain significantly more neurons than the left, particularly neurons with somata having sectioned areas 200-400 microm2 and longest diameters 15-25 microm. Such neurons appear to be homogenously distributed because sections of the right vagal ganglia did not show specific areas of neuronal density compared with those of the left. Neonatal capsaicin treatment reduced the number of neurons in both the left and right ganglia to about 30% of controls. Capsaicin destroyed neurons with sectioned areas of 100-600 microm2 and longest diameters of 15-35 microm, but had no statistically significant effects on larger neurons.

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“…Like most abdominal organs, the pancreas is innervated by sensory fibers from both the nodose (via the vagal nerve) and spinal ganglia (via splanchnic nerves) (3)(4)(5)(6)(7). In rodent models of acute or chronic pancreatitis, blockade of primary afferents from both nodose and spinal ganglia can moderate or prevent inflammation (8,9) as well as associated pathology, even if done after the inciting injury (10,11).…”

mentioning

confidence: 99%

Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer

Saloman

Albers

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

282

243

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Pancreatic ductal adenocarcinoma (PDAC) is characterized by an exuberant inflammatory desmoplastic response. The PDAC microenvironment is complex, containing both pro-and antitumorigenic elements, and remains to be fully characterized. Here, we show that sensory neurons, an under-studied cohort of the pancreas tumor stroma, play a significant role in the initiation and progression of the early stages of PDAC. Using a well-established autochthonous model of PDAC (PKC), we show that inflammation and neuronal damage in the peripheral and central nervous system (CNS) occurs as early as the pancreatic intraepithelial neoplasia (PanIN) 2 stage. Also at the PanIN2 stage, pancreas acinar-derived cells frequently invade along sensory neurons into the spinal cord and migrate caudally to the lower thoracic and upper lumbar regions. Sensory neuron ablation by neonatal capsaicin injection prevented perineural invasion (PNI), astrocyte activation, and neuronal damage, suggesting that sensory neurons convey inflammatory signals from Kras-induced pancreatic neoplasia to the CNS. Neuron ablation in PKC mice also significantly delayed PanIN formation and ultimately prolonged survival compared with vehicle-treated controls (median survival, 7.8 vs. 4.5 mo; P = 0.001). These data establish a reciprocal signaling loop between the pancreas and nervous system, including the CNS, that supports inflammation associated with oncogenic Kras-induced neoplasia. Thus, pancreatic sensory neurons comprise an important stromal cell population that supports the initiation and progression of PDAC and may represent a potential target for prevention in high-risk populations.sensory neuron | pancreatic ductal adenocarcinoma | tumorigenesis | inflammation | PanIN P ancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with a median survival of ∼6 mo from diagnosis (National Cancer Institute). A number of unique features distinguish PDAC from other carcinomas, but the most striking is the exuberant desmoplastic infiltrate within tumors. This compartment exhibits an array of cell types, including activated myofibroblasts and myeloid-derived cells. Indeed, this inflammatory infiltrate is present at the inception of neoplasia and accumulates at a near exponential rate during progression to carcinoma and tumor formation. It provides a complex balance of pro-and antitumorigenic signals to neoplastic cells (and also to each other) that is a focus of intense investigation. The pancreas tumor microenvironment has been studied previously, but new tools [genetically engineered mouse models (GEMs) that faithfully recapitulate the salient features of human PDAC] now allow for a careful dissection of the stroma. Using these models, we showed that generalized inflammation is required for the development of precancerous pancreatic intraepithelial neoplasias (1) and that Hedgehog-dependent stromal elements, including activated myofibroblasts, serve to constrain tumor growth and spread (2). Other cellular components of the pancreatic inflammatory str...

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Capsaicin-sensitive vagal afferent neurons innervating the rat pancreas

Cited by 22 publications

References 14 publications

The dorsal motor nucleus of the vagus and regulation of pancreatic secretory function

The dorsal motor nucleus of the vagus and regulation of pancreatic secretory function

A quantitative investigation of the effects of neonatal capsaicin treatment on vagal afferent neurons in the rat

Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer

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