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Münzberg H, Berthoud HR, Neuhuber WL. Sensory spinal interoceptive pathways and energy balance regulation. Mol Metab 2023; 78:101817. [PMID: 37806487 PMCID: PMC10590858 DOI: 10.1016/j.molmet.2023.101817] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 10/02/2023] [Accepted: 10/03/2023] [Indexed: 10/10/2023] Open
Abstract
Interoception plays an important role in homeostatic regulation of energy intake and metabolism. Major interoceptive pathways include gut-to-brain and adipose tissue-to brain signaling via vagal sensory nerves and hormones, such as leptin. However, signaling via spinal sensory neurons is rapidly emerging as an additional important signaling pathway. Here we provide an in-depth review of the known anatomy and functions of spinal sensory pathways and discuss potential mechanisms relevant for energy balance homeostasis in health and disease. Because sensory innervation by dorsal root ganglia (DRG) neurons goes far beyond vagally innervated viscera and includes adipose tissue, skeletal muscle, and skin, it is in a position to provide much more complete metabolic information to the brain. Molecular and anatomical identification of function specific DRG neurons will be important steps in designing pharmacological and neuromodulation approaches to affect energy balance regulation in disease states such as obesity, diabetes, and cancer.
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Affiliation(s)
- Heike Münzberg
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
| | - Hans-Rudolf Berthoud
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
| | - Winfried L Neuhuber
- Institute for Anatomy and Cell Biology, Friedrich-Alexander University, Erlangen, Germany.
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Hirakawa M, Yokoyama T, Yamamoto Y, Saino T. Distribution and morphology of P2X3-immunoreactive subserosal afferent nerve endings in the rat gastric antrum. J Comp Neurol 2020; 529:2014-2028. [PMID: 33190284 DOI: 10.1002/cne.25069] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 10/27/2020] [Accepted: 11/09/2020] [Indexed: 12/15/2022]
Abstract
The present study investigated the morphological characteristics of subserosal afferent nerve endings with immunoreactivity for the P2X3 purinoceptor (P2X3) in the rat stomach by immunohistochemistry of whole-mount preparations using confocal scanning laser microscopy. P2X3 immunoreactivity was observed in subserosal nerve endings proximal and lateral to the gastric sling muscles in the distal antrum of the lesser curvature. Parent axons ramified into several lamellar processes to form net-like complex structures that extended two-dimensionally in every direction on the surface of the longitudinal smooth muscle layer. The axon terminals in the periphery of P2X3-immunoreactive net-like structures were flat and looped or leaf-like in shape. Some net-like lamellar structures and their axon terminals with P2X3 immunoreactivity were also immunoreactive for P2X2. P2X3-immunoreactive nerve fibers forming net-like terminal structures were closely surrounded by S100B-immunoreactive terminal Schwann cells, whereas axon terminals twined around these cells and extended club-, knob-, or thread-like protrusions in the surrounding tissues. Furthermore, a retrograde tracing method using fast blue dye indicated that most of these nerve endings originated from the nodose ganglia of the vagus nerve. These results suggest that P2X3-immunoreactive subserosal nerve endings have morphological characteristics of mechanoreceptors and contribute to sensation of a mechanical deformation of the distal antral wall associated with antral peristalsis.
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Affiliation(s)
- Masato Hirakawa
- Department of Anatomy (Cell Biology), Iwate Medical University, Yahaba-cho, Japan
| | - Takuya Yokoyama
- Department of Anatomy (Cell Biology), Iwate Medical University, Yahaba-cho, Japan
| | - Yoshio Yamamoto
- Laboratory of Veterinary Anatomy and Cell Biology, Faculty of Agriculture, Iwate University, Morioka, Japan
| | - Tomoyuki Saino
- Department of Anatomy (Cell Biology), Iwate Medical University, Yahaba-cho, Japan
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Rytel L, Całka J. Neuropeptide profile changes in sensory neurones after partial prepyloric resection in pigs. Ann Anat 2016; 206:48-56. [PMID: 27142347 DOI: 10.1016/j.aanat.2016.03.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2015] [Revised: 03/04/2016] [Accepted: 03/07/2016] [Indexed: 12/20/2022]
Abstract
This report details the first identification of the sources of sensory innervation of the porcine stomach prepyloric region. The Fast Blue (FB) retrograde tracing technique detected the sensory prepyloric neurons in the bilateral nodose ganglia (NGs) as well as thoracic dorsal root ganglia (DRGs). Double-labelling immunofluorescence demonstrated expression of substance P (SP), calcitonin gene-related peptide (CGRP), neuronal isoform of nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP) and galanin (GAL) in both NGs and DRGs. Additionally, we found that partial resection of the stomach prepyloric area increased expression of the SP, CGRP, NOS, VIP and GAL in the prepyloric sensory neurons. In the control left NGs, both a higher total number of FB-positive perikarya as well as a higher percentage of the peptides expressing prepyloric neurons were visualized than in the right NGs. However, compared to the control group, prepyloric resection evoked greater increases in peptide expression in the right-side NGs sensory neurons. In the ganglia of this side, the proportion of the SP-IR perikarya increased by approximately 15%, while CGRP-IR increased by 28%, NOS-IR 14%, VIP-IR 43% and GAL-IR 13%. On the opposite left side, the ganglia proportion of the CGRP-IR perikarya increased by approximately 10%, while NOS-IR increased by 3%, VIP-IR 36% and GAL-IR by 2%. The only decrease (by 5%) was observed in the case of SP expression. We also found that 92% of the sensory neurons originated from NGs and 8% from DRGs. Our results indicate that, in the pig, SP, CGRP, NOS, VIP and GAL participate in the vagal sensory transduction from the stomach prepyloric area. Moreover, increased expression of the peptides and neuronal isoform of nitric oxide synthase in the sensory neurons following transection of their peripheral dendrites suggests their possible participation in the neuronal recovery and/or reinnervation process.
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Affiliation(s)
- L Rytel
- Department of Clinical Physiology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Olsztyn, Poland.
| | - J Całka
- Department of Clinical Physiology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Olsztyn, Poland
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Sleeve gastrectomy and Roux-en-Y gastric bypass alter the gut-brain communication. Neural Plast 2015; 2015:601985. [PMID: 25722893 PMCID: PMC4333325 DOI: 10.1155/2015/601985] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2014] [Revised: 10/15/2014] [Accepted: 10/17/2014] [Indexed: 12/15/2022] Open
Abstract
This study investigated the anatomical integrity of vagal innervation of the gastrointestinal tract following vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) operations. The retrograde tracer fast blue (FB) was injected into the stomach to label vagal neurons originating from nodose ganglion (NG) and dorsal motor nucleus of the vagus (DMV). Microglia activation was determined by quantifying changes in the fluorescent staining of hindbrain sections against an ionizing calcium adapter binding molecule 1 (Iba1). Reorganization of vagal afferents in the hindbrain was studied by fluorescent staining against isolectin 4 (IB4). The density of Iba1- and IB4-immunoreactivity was analyzed using Nikon Elements software. There was no difference in the number of FB-labeled neurons located in NG and DMV between VSG and VSG-sham rats. RYGB, but not RYGB-sham rats, showed a dramatic reduction in number of FB-labeled neurons located in the NG and DMV. VSG increased, while the RYGB operation decreased, the density of vagal afferents in the nucleus tractus solitarius (NTS). The RYGB operation, but not the VSG procedure, significantly activated microglia in the NTS and DMV. Results of this study show that the RYGB, but not the VSG procedure, triggers microglia activation in vagal structures and remodels gut-brain communication.
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Sangari SK, Khatri K. Pre and postganglionic innervation of rat adrenal gland by fluorescent tract tracer – Fast blue. J ANAT SOC INDIA 2014. [DOI: 10.1016/j.jasi.2014.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Liu LS, Shenoy M, Pasricha PJ. The analgesic effects of the GABAB receptor agonist, baclofen, in a rodent model of functional dyspepsia. Neurogastroenterol Motil 2011; 23:356-61, e160-1. [PMID: 21199535 DOI: 10.1111/j.1365-2982.2010.01649.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The amino acid γ-aminobutyric acid (GABA) is an important modulator of pain but its role in visceral pain syndromes is just beginning to be studied. Our aims were to investigate the effect and mechanism of action of the GABA(B) receptor agonist, baclofen, on gastric hypersensitivity in a validated rat model of functional dyspepsia (FD). METHODS 10-day-old male rats received 0.2 mL of 0.1% iodoacetamide in 2% sucrose daily by oral gavages for 6 days. Control group received 2% sucrose. At 8-10 weeks rats treated with baclofen (0.3, 1, and 3 mg kg(-1) bw) or saline were tested for behavioral and electromyographic (EMG) visceromotor responses; gastric spinal afferent nerve activity to graded gastric distention and Fos protein expression in dorsal horn of spinal cord segments T8-T10 to noxious gastric distention. KEY RESULTS Baclofen administration was associated with a significant attenuation of the behavioral and EMG responses (at 1 and 3 mg kg(-1)) and expression of Fos in T8 and T9 segments in neonatal iodoacetamide sensitized rats. However, baclofen administration did not significantly affect splanchnic nerve activity to gastric distention. Baclofen (3 mg kg(-1)) also significantly reduced the expression of spinal Fos in response to gastric distention in control rats to a lesser extent than sensitized rats. CONCLUSIONS & INFERENCES Baclofen is effective in attenuating pain associated responses in an experimental model of FD and appears to act by central mechanisms. These results provide a basis for clinical trials of this drug in FD patients.
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Affiliation(s)
- L S Liu
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA 94305-5187, USA
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Tan LL, Bornstein JC, Anderson CR. Neurochemical and morphological phenotypes of vagal afferent neurons innervating the adult mouse jejunum. Neurogastroenterol Motil 2009; 21:994-1001. [PMID: 19413682 DOI: 10.1111/j.1365-2982.2009.01322.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Whilst much is known about the function and influence of vagal afferents on the mammalian upper gastrointestinal tract, the phenotypes of the different types of vagal afferent neurons innervating the jejunum is unknown. We have previously shown that spinal afferents supplying the jejunum are predominantly medium-sized sensory neurons that express specific combinations of transient receptor potential vanilloid type 1 (TRPV1), neuronal nitric oxide synthase (NOS) and calcitonin-gene related peptide (CGRP) and that they lack binding for isolectin B4 (IB4). This study aimed to identify the chemical phenotypes and somal sizes of jejunal afferent neurons in the mouse vagal ganglion. Jejunal vagal afferents were identified by retrograde labelling with sub-serosal injections of cholera toxin B (CTB) into the jejunal wall and assessed for IB4-binding, TRPV1-, NOS- and CGRP-immunoreactivities using fluorescent microscopy. Almost all (99%) of CTB-labelled vagal afferent neurons were small- and medium-sized sensory cells. Most (81%) jejunal vagal afferents bound IB4 but fewer (32%) expressed TRPV1. A quarter (25%) of those that bound IB4 co-expressed TRPV1-immunoreactivity whilst 77% of TRPV1-expressing jejunal vagal afferent neurons bound IB4. NOS (0%) and CGRP (0%) expression was absent from all CTB-labelled cells examined. In conclusion, vagal afferents innervating the jejunum differ in their expression of IB4, TRPV1, CGRP and NOS from their spinal counterparts, suggesting that the peripheral endings for extrinsic sensory neurons terminating within the enteric nervous system can be identified selectively.
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Affiliation(s)
- L L Tan
- Department of Physiology, University of Melbourne, Parkville, VIC, Australia.
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Abstract
Gastric reflexes are mediated mainly by vago-vagal reflex circuits in the caudal medulla. Despite the fact that brainstem vago-vagal circuitry remains intact after spinal cord injury (SCI), patients with SCI at the cervical level most often present gastric stasis with an increased risk of reflux and aspiration of gastric contents. Using a miniature strain gauge sutured to the gastric surface; we tested gastric motility and reflexive gastric relaxation following oesophageal distension (oesophageal-gastric relaxation reflex) in animals 3 days after a severe spinal contusion at either the third or ninth thoracic spinal segment (acute T3- or T9 SCI, respectively). Both basal gastric motility and the oesophageal-gastric relaxation reflex were significantly diminished in animals with T3 SCI. Conversely, both basal gastric motility and the oesophageal-gastric relaxation reflex were not significantly reduced in T9 SCI animals compared to controls. The reduced gastric motility and oesophageal-gastric reflex in T3 SCI rats was not ameliorated by celiac sympathectomy. Our results show that gastric stasis following acute SCI is independent of altered spinal sympathetic input to the stomach caudal to the lesion. Our data suggest that SCI may alter the sensitivity of vagal reflex function, perhaps by interrupting ascending spinosolitary input to brainstem vagal nuclei.
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Affiliation(s)
- M Tong
- Neurotrauma and Nutrition Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA
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Distinct chemical classes of medium-sized transient receptor potential channel vanilloid 1-immunoreactive dorsal root ganglion neurons innervate the adult mouse jejunum and colon. Neuroscience 2008; 156:334-43. [DOI: 10.1016/j.neuroscience.2008.06.071] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2008] [Revised: 05/20/2008] [Accepted: 06/28/2008] [Indexed: 11/17/2022]
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Qin C, Chen JDZ, Zhang J, Foreman RD. Duodenal afferent input converges onto T9-T10 spinal neurons responding to gastric distension in rats. Brain Res 2007; 1186:180-7. [PMID: 17997398 DOI: 10.1016/j.brainres.2007.10.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2007] [Revised: 09/26/2007] [Accepted: 10/06/2007] [Indexed: 01/08/2023]
Abstract
Clinically, the overlap of gastroduodenal symptoms, such as visceral pain or hypersensitivity, is often observed in functional gastrointestinal disorders. The underlying mechanism may be related to intraspinal neuronal processing of noxious convergent inputs from the stomach and the intestine. The purpose of this study was to examine whether single low thoracic (T9-T10) spinal neurons responded to both gastric and duodenal mechanical stimulation. Extracellular potentials of single T9-T10 spinal neurons were recorded in pentobarbital anesthetized, paralyzed, and ventilated male rats. Graded gastric distensions (GD, 20, 40, 60 mm Hg, 20 s) were induced by air inflation of a latex balloon surgically placed in the stomach. Graded duodenal distensions (DD, 0.2, 0.4, 0.6 ml, 20 s) were produced by water inflation of a latex balloon placed into the duodenum. Of 70 deeper (depth from dorsal surface of spinal cord: 0.3-1.2 mm) spinal neurons responsive to noxious GD (> or =40 mm Hg), 44(63%) also responded to noxious DD (> or =0.4 ml). Similarly, 13/17 (76%) superficial neurons (depth <0.3 mm) responded to both GD and DD. Of 57 gastroduodenal convergent neurons, 41 (72%) had excitatory and 6 had inhibitory responses to both GD and DD; the remaining neurons exhibited multiple patterns of excitation and inhibition. 43/57 (75%) gastroduodenal convergent neurons had low-threshold (< or =20 mm Hg) responses to GD, whereas 42/57 (74%) of these neurons had high-threshold (> or =0.4 ml) responses to DD. In addition, 34/40 (85%) gastroduodenal convergent neurons had somatic receptive fields on the back, flank, and medial/lateral abdominal areas. These results suggested that superficial and deeper T9-T10 spinal neurons received innocuous and/or noxious convergent inputs from mechanical stimulation of the stomach and duodenum. Gastroduodenal convergent spinal neurons might contribute to intraspinal sensory transmission for cross-organ afferent-afferent communication between the stomach and duodenum and play a role in visceral nociception and reflexes.
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Affiliation(s)
- Chao Qin
- Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA.
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Qin C, Farber JP, Foreman RD. Gastrocardiac afferent convergence in upper thoracic spinal neurons: a central mechanism of postprandial angina pectoris. THE JOURNAL OF PAIN 2007; 8:522-9. [PMID: 17434802 DOI: 10.1016/j.jpain.2007.02.428] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2006] [Revised: 02/06/2007] [Accepted: 02/22/2007] [Indexed: 11/23/2022]
Abstract
UNLABELLED The aim of this study was to examine whether gastric afferent information converged onto upper thoracic spinal neurons that received noxious cardiac input. Extracellular potentials of single upper thoracic (T3) spinal neurons were recorded in pentobarbital-anesthetized, paralyzed, ventilated male rats. Gastric distension (GD) (20, 40, 60 mm Hg, 20 seconds) was produced by air inflation of a latex balloon surgically placed in the stomach. A catheter was placed in the pericardial sac to administer bradykinin solution (10 microg/mL, 0.2 mL, 1 minute) as a noxious cardiac stimulus. Noxious GD (> or =40 mm Hg) altered activity of 26 of 31 (84%) spinal neurons receiving cardiac input. Twenty-two (85%) gastrocardiac convergent neurons were excited, and 1 neuron was inhibited by both intrapericardial bradykinin and GD; the remainder exhibited biphasic response patterns. Twenty-three of 26 (88%) gastrocardiac neurons also received convergent somatic input from the chest, triceps, and upper back areas. Bilateral cervical vagotomy did not significantly affect excitatory responses to GD in 5 of 5 neurons tested. Spinal transection at the C1 segment after vagotomy did not affect excitatory responses to GD in 3 of 4 neurons but abolished the GD response in 1 neuron. These data showed that a gastric stimulus excited T3 spinal neurons with noxious cardiac input primarily by way of intraspinal ascending pathways. PERSPECTIVE Convergence of gastric afferent input onto upper thoracic spinal neurons receiving noxious cardiac input that was observed in the present study may provide a spinal mechanism that explains stomach-heart cross-organ communication, such as postprandial triggering and worsening of angina pectoris in patients with coronary artery disease.
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Affiliation(s)
- Chao Qin
- Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190, USA.
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Characterization of T9-T10 spinal neurons with duodenal input and modulation by gastric electrical stimulation in rats. Brain Res 2007; 1152:75-86. [PMID: 17433808 DOI: 10.1016/j.brainres.2007.03.034] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2007] [Revised: 03/12/2007] [Accepted: 03/12/2007] [Indexed: 10/23/2022]
Abstract
Gastric electrical stimulation (GES) has been suggested as a therapy for patients with gastric motility disorders or morbid obesity. However, it is unclear whether GES also affects intestinal sensory and motor functions. Furthermore, little is known about intraspinal visceroreceptive transmission and processing for duodenal afferent information. The aims of this study were to characterize responses of thoracic spinal neurons to duodenal distension, to determine the afferent pathway and to examine the effects of GES on activity of these neurons. Extracellular potentials of single T9-T10 spinal neurons were recorded in pentobarbital anesthetized, paralyzed, ventilated male rats (n=19). Graded duodenal distension (DD, 0.2-0.6 ml, 20 s) was produced by water inflation of a latex balloon surgically placed into the duodenum. One pair of platinum electrodes (1.0-1.5 cm apart) was sutured onto the serosal surface of the lesser curvature of the stomach. GES with four sets of parameters was applied for one minute: GES-A (6 mA, 0.3 ms, 40 Hz, 2 s on, 3 s off), GES-B (6 mA, 0.3 ms, 14 Hz, 0.1 s on, 5 s off), GES-C (6 mA, 3 ms, 40 Hz, 2 s on, 3 s off) and GES-D (6 mA, 200 ms, 12 pulses/min). Results showed that 33/117 (28%) spinal neurons responded to noxious DD (0.4 ml, 20 s). Of these, 7 (6%) neurons had low-threshold responses to DD (<or=0.2 ml) and 26 (22%) had high-threshold responses to DD (>or=0.4 ml). DD-responsive spinal neurons were encountered more frequently in deeper (depth: 0.3-1.2 mm) than in superficial laminae (depth: <0.3 mm) of the dorsal horn (24/67 vs. 9/50, P<0.05). DD excited all 9 superficial neurons. In contrast, 20 deeper neurons were excited and 4 neurons were inhibited by DD. Activity of DD-responsive neurons was affected more frequently with GES-C (13/15, 87%) than GES-A (6/16, 38%), -B (3/15, 20%) and -D (5/14, 36%) (P<0.01). Bilateral cervical vagotomy did not significantly alter the effects of DD and GES on 5/5 neurons. Resiniferatoxin (2.0 microg/kg, i.v.), an ultrapotent agonist of transient receptor potential vanilloid receptor-1 (TRPV1), abolished DD responses and GES effects on all neurons examined in vagotomized rats. Additionally, 29/33 (88%) DD-responsive neurons received inputs from somatic receptive fields on the back, flank and medial/lateral abdominal areas. It was concluded that GES mainly exerted an excitatory effect on T9-T10 spinal neurons with duodenal input transmitted by sympathetic afferent fibers expressing TRPV1; spinal neuronal responses to GES were strengthened with an increased pulse width and/or frequency of stimulation; T9-T10 spinal neurons processed input from the duodenum and might mediate effects of GES on duodenal sensation and motility.
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Li YQ, Zhu B, Rong PJ, Ben H, Li YH. Effective regularity in modulation on gastric motility induced by different acupoint stimulation. World J Gastroenterol 2006; 12:7642-8. [PMID: 17171793 PMCID: PMC4088046 DOI: 10.3748/wjg.v12.i47.7642] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate whether manual acupuncture at representative acupoints in different parts of the body can modulate responses of gastric motility in rats and regular effects in different acupoint stimulation.
METHODS: The gastric motor activity of rats was recorded by the intrapyloric balloon. The changes of gastric motility induced by the stimulation were compared with the background activity in intragastric pressure and/or waves of gastric contraction recorded before any stimulation. Morphological study was also conducted by observing the Evans dye extravasation in the skin after mustard oil injection into the intragastric mucous membrane to certify cutaneous innervations of blue dots related to gastric segmental innervations.
RESULTS: In all six rats that received mustard oil injections into intragastric mucosa, small blue dots appeared in the skin over the whole abdomen, but mainly in peri-midline upper- and middle- abdomen and middle-back, a few in thigh and groin. It may speculate that cutaneous innervations of blue dots have the same distribution as gastric segmental innervations. Acu-stimulation in acupoints of head-neck, four limbs, upper chest-dorsum and lower-dorsum induced markedly augmentation of gastric motility (acupoints on head-neck such as St-2: n = 16, 105.19 ± 1.36 vs 112.25 ± 2.02 and St-3: n = 14, 101.5 ± 1.75 vs 109.36 ± 1.8; acupoints on limbs such as Sp-6: n = 19, 100.74 ± 1.54 vs 110.26 ± 3.88; St-32: n = 17, 103.59 ± 1.64 vs 108.24 ± 2.41; St-36: n = 16, 104.81 ± 1.72 vs 110.81 ± 2.74 and Li-11: n = 17, 106.47 ± 2.61 vs 114.77 ± 3.77, P < 0.05-0.001). Vigorous inhibitory regulations of gastric motility induced by acu-stimulation applied in acupoints on whole abdomen and middle-dorsum were significantly different as compared with the controls before acu-stimulation (abdomen acupoints such as Cv-12: n = 11, 109.36 ± 2.09 vs 101 ± 2.21; Cv-6: n = 18, 104.39 ± 1.42 vs 91.83 ± 3.22 and St-21: n = 12, 107 ± 2.97 vs 98.58 ± 2.81; acupoints on middle-dorsum such as Bl-17: n = 19, 100.63 ± 1.4 vs 92.21 ± 2.07 and Bl-21: n = 19, 103.84 ± 1.48 vs 97.58 ± 2.16, P < 0.05-0.001).
CONCLUSION: Regular regulatory effects of facilitation and inhibition on gastric motility appear to be somatotopically organized in the acupoints of whole body, and the effective regularity of site-special acupoints on gastric motility is involved in segmental innervations between stomach and acupoints.
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Affiliation(s)
- Yu-Qing Li
- Institute of Acupuncture-moxibustion, China Academy of Chinese Medical Sciences, 16 Nanxiaojie of Dongzhimennei, Beijing 100700, China
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Qin C, Chen JDZ, Zhang J, Foreman RD. Modulatory effects and afferent pathways of gastric electrical stimulation on rat thoracic spinal neurons receiving input from the stomach. Neurosci Res 2006; 57:29-39. [PMID: 17046091 PMCID: PMC1855190 DOI: 10.1016/j.neures.2006.09.003] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2006] [Revised: 08/29/2006] [Accepted: 09/07/2006] [Indexed: 01/17/2023]
Abstract
Gastric electrical stimulation (GES) has been suggested as a potential therapy for patients with obesity or gastric motility disorders. The aim of this study was to investigate the spinal mechanism of GES effects on gastric functions. Extracellular potentials of single spinal (T9-T10) neurons were recorded in pentobarbital anesthetized, paralyzed, ventilated male rats (n=19). Gastric distension (GD) was produced by air inflation of a balloon. One pair of platinum electrodes (1.0-1.5cm apart) was sutured onto the serosal surface of the lesser curvature of the stomach. GES with four sets of parameters was applied for 1min: GES-A (6mA, 0.3ms, 40Hz, 2s on, 3s off), GES-B (6mA, 0.3ms, 14Hz, 0.1s on, 5s off), GES-C (6mA, 3ms, 40Hz, 2s on, 3s off), GES-D (6mA, 200ms, 12pulses/min). 62/158 (39%) spinal neurons responded to GD (20, 40, 60mmHg, 20s. Most GD-responsive neurons (n=43) had excitatory responses; the remainder had inhibitory (n=12) or biphasic responses (n=7). GES-A, -B, -C and -D affected activity of 12/33 (36%), 4/31 (13%), 22/29 (76%) and 13/30 (43%) GD-responsive neurons, respectively. Bilateral cervical vagotomy did not significantly alter mean excitatory neuronal responses to GD (n=5) or GES (n=6). Resiniferatoxin (2.0microg/kg, i.v.), an ultrapotent agonist of vanilloid receptor-1, abolished excitatory responses to GD and GES in 4/4 neurons recorded in vagotomized rats. The results suggested that GES mainly had an excitatory effect on T9-T10 spinal neurons with gastric inputs; neuronal responses to GES were strengthened with stimulation at an increased pulse width and/or number of pulses. The modulatory effect of GES involved thoracic spinal (sympathetic) afferent fibers containing vanilloid receptor-1.
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Affiliation(s)
- Chao Qin
- Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA.
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Abstract
Satiation for food comprises the physiological processes that result in the termination of eating. Satiation is evoked by physical and chemical qualities of ingested food, which trigger afferent signals to the brain from multiple sites in the GI tract, including the stomach, the proximal small intestine, the distal small intestine and the colon. The physiological nature of each signal's contribution to satiation and overall control of food intake is likely to vary, depending on the level of the GI tract from which the signal arises. This article is a critical, though non-exhaustive, review of our current understanding of the mechanisms and adaptive value of satiation signals from the stomach and intestine.
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Affiliation(s)
- Robert C Ritter
- Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, and Programs in Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6520, USA.
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16
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Qin C, Chandler MJ, Miller KE, Foreman RD. Responses and afferent pathways of C(1)-C(2) spinal neurons to gastric distension in rats. Auton Neurosci 2003; 104:128-36. [PMID: 12648614 DOI: 10.1016/s1566-0702(03)00002-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Some evidence shows that the upper cervical spinal cord might play an important role in propriospinal processing as a sensory filter and modulator for visceral afferents. The aims of this study were to determine (1). the responses of C(1)-C(2) spinal neurons to gastric distension and (2). the relative contribution of vagal and spinal visceral afferent pathways for transmission of gastric input to the upper cervical spinal cord. Extracellular potentials of single C(1)-C(2) spinal neurons were recorded in pentobarbital anesthetized male rats. Graded gastric distension (20-80 mm Hg) was produced by air inflation of a latex balloon surgically placed in the stomach. Sixteen percent of the neurons (32/198) responded to gastric distension; 17 neurons were excited and 15 neurons were inhibited by gastric distension. Spontaneous activity of neurons with inhibitory responses was higher than those neurons with excitatory responses (18.1+/-2.7 vs. 3.8+/-1.7 impulses s(-1), p<0.001). Twenty-eight of thirty-two (87.5%) neurons responded to mechanical stimulation of somatic fields on head, neck, ears or shoulder. Most lesion sites of neurons with excitatory responses were found in laminae V, VII; however, neurons with inhibitory responses were in laminae III, IV. Bilateral cervical vagotomy abolished responses of 4/8 neurons tested. Spinal transection at C(6)-C(7) abolished responses of the other four neurons that still responded to gastric distension after bilateral vagotomy. Results of these data supported the concept that a group of C(1)-C(2) spinal neurons might play a role in processing sensory information from the stomach that travels in vagal and spinal visceral afferent fibers.
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Affiliation(s)
- Chao Qin
- Department of Physiology, University of Oklahoma Health Sciences Center, PO Box 26901, Oklahoma City, OK 73190, USA.
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17
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Nakano M, Kishida R, Funakoshi K, Tsukagoshi M, Goris RC, Kadota T, Atobe Y, Hisajima T. Central projections of thoracic splanchnic and somatic nerves and the location of sympathetic preganglionic neurons in Xenopus laevis. J Comp Neurol 2003; 456:321-37. [PMID: 12532405 DOI: 10.1002/cne.10514] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The central and peripheral organization of thoracic visceral and somatic nervous elements was studied by applying dextran amines to the proximal cut ends of the thoracic splanchnic and somatic nerves in Xenopus laevis. Many labeled dorsal root ganglion cells of visceral afferents, and all somatic afferents, were located in a single ganglion of one spinal segment, and the two types of cells were distributed topographically within the ganglion. The labeled sympathetic preganglionic neurons were located predominantly in the same area of the thoracic spinal gray as in other frogs and in mammals. The labeled visceral afferents projected to Lissauer's tract and the dorsal funiculus. The visceral fibers of the tract ascended to the level of the subcerebellar area, supplying collateral branches to the lateral one-third of the dorsal horn and to the area of brainstem nuclei, including lateral cervical and descending trigeminal nucleus, and descended to the filum terminale. The visceral fibers of the dorsal funiculus were distributed to the dorsal column nucleus and the solitary tract. A similar longitudinal projection was also seen in the somatic afferents. The dual central pathway of thoracic primary afferents in the anuran spinal cord is a property held in common with mammals, but the widespread rostrocaudal projection through Lissauer's tract may be a characteristic of the anuran central nervous system. In frogs, the direct transmission of primary afferent information to an extremely wide area of the central nervous system may be important for prompt assessment of environmental factors and control of body functions.
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Affiliation(s)
- Masato Nakano
- Department of System Neuroanatomy, Yokohama City University School of Medicine, Yokohama, 236-0004 Japan.
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18
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Ozaki N, Gebhart GF. Characterization of mechanosensitive splanchnic nerve afferent fibers innervating the rat stomach. Am J Physiol Gastrointest Liver Physiol 2001; 281:G1449-59. [PMID: 11705750 DOI: 10.1152/ajpgi.2001.281.6.g1449] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Splanchnic nerve fibers innervating the stomach were studied in anesthetized rats; 997 fibers in the T(9) or T(10) dorsal roots were identified by electrical stimulation of the splanchnic nerve. Thirty-one fibers responded to gastric distension. Extrapolated response thresholds ranged between 0 and 53 mmHg; seven fibers had thresholds for response > or =30 mmHg. Thermo- and/or chemosensitivity was tested in 18 of the 31 fibers. Four of twelve fibers responded to intragastric perfusion of heated saline; none of eight fibers tested responded to perfusion of cold saline. Infusion of glucose, L-arginine, or potassium oleate produced no change in resting activity. Intragastric instillation of 12% glycerol or an inflammatory soup (bradykinin 10(-5) M, PGE(2) 10(-5) M, serotonin 10(-5) M, histamine 10(-5) M, and KCl 10(-3) M) and prior heat stimulation sensitized responses to distension. The results reveal the presence of low- and high-threshold mechanosensitive fibers in the splanchnic innervation of the stomach. These fibers have the ability to sensitize, and they likely contribute to pain and altered sensations that can arise from the stomach.
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Affiliation(s)
- N Ozaki
- Department of Pharmacology, College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA
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19
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Baird JP, Travers JB, Travers SP. Parametric analysis of gastric distension responses in the parabrachial nucleus. Am J Physiol Regul Integr Comp Physiol 2001; 281:R1568-80. [PMID: 11641130 DOI: 10.1152/ajpregu.2001.281.5.r1568] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The parabrachial nucleus (PBN) is regarded as an important locus for the processing and integration of sensory inputs from oral, gastrointestinal, and postabsorptive receptor sites and is thus thought to play an important role in regulating food intake. Gastric distension is an important satiation cue; however, such responses have been qualitatively characterized only over a limited area of the PBN. To more fully characterize gastric distension responses throughout the PBN, the responses of single units to gastric distension were tested using computer-controlled balloon inflation (3-18 ml air) in pentobarbital sodium- and/or urethan-anesthetized male rats. Distension-responsive neurons were indeed distributed throughout the nucleus from rostral areas typically considered to be visceral to more caudal areas associated with gustatory function, providing further anatomical support for the hypothesis that the PBN integrates taste and visceral signals that control feeding. Most PBN neurons had thresholds of 6 ml or less, similar to vagal afferent fibers. However, in contrast to the periphery, there were both excitatory and inhibitory responses. Increases in volume were associated with two distinct effects. First, as volume increased, the response rate increased; second, the duration of the response increased. In fact, in a subset of cells, responses to gastric distension lasted well beyond the stimulation period, particularly at larger volumes. Prolonged gastric distension responses are not common in the periphery and may constitute a central mechanism that contributes to satiation processes.
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Affiliation(s)
- J P Baird
- Oral Biology, College of Dentistry, Ohio State University, Columbus, Ohio 43210, USA.
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20
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Abstract
The afferent innervation of the suprarenal gland was studied by using a fluorescent tract tracer in the adult albino rat. The left suprarenal gland was injected slowly with 5 microl of 2% aqueous suspension of Fast blue. After a survival period of 4-5 days, the dorsal root ganglia were dissected out and 15-microm-thick plastic (JB 4) sections were examined under the fluorescent microscope. The labelled neurons were seen from the third thoracic to second lumbar dorsal root ganglia, ipsilateral to the site of injection with maximum concentration from T6 to T11. These primary sensory neurons were round to oval in shape, varied from 7 microm to 40 microm in size, and were distributed randomly in the dorsal root ganglia. The labelling of the primary sensory neurons in the dorsal root ganglia confirms the presence of sensory nerve endings in the suprarenal gland that may be responsible for the vascular distension and hormonal release.
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Affiliation(s)
- S K Sangari
- Department of Anatomy, University College of Medical Sciences and G.T.B. Hospital, Delhi, India
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21
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Wang HF, Robertson B, Grant G. Anterograde transport of horseradish-peroxidase conjugated isolectin B4 from Griffonia simplicifolia I in spinal primary sensory neurons of the rat. Brain Res 1998; 811:34-9. [PMID: 9804881 DOI: 10.1016/s0006-8993(98)00916-0] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
Anterograde transport of the isolectin B4 from Griffonia simplicifolia I (B4) conjugated to horseradish peroxidase (HRP) was investigated in rat somatic and visceral primary sensory neurons at different spinal levels. Injection of B4-HRP into the L5 dorsal root ganglion (DRG) resulted in labelling in the sural nerve, but not in the gastrocnemius nerves. Free nerve endings and lanceolate-like nerve endings were labelled in the lateral hindpaw skin. Labelled fibres were also observed in the greater splanchnic nerve following B4-HRP injection into the T10-11 DRGs. Electron microscopic examination of the labelled nerves showed that B4-HRP labelled exclusively unmyelinated axons. In the spinal cord, labelling was observed in the superficial dorsal horn, and additionally, although much more sparse, in the medial and lateral collateral projections following injections into the T10-11 DRGs. The results suggest that B4-HRP should be a suitable anterograde tracer of unmyelinated cutaneous and splanchnic but not muscle primary afferent fibres.
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Affiliation(s)
- H F Wang
- Department of Neuroscience, Karolinska Institutet, Doktorsringen 17, S-171 77, Stockholm, Sweden
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22
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Traub RJ, Sengupta JN, Gebhart GF. Differential c-fos expression in the nucleus of the solitary tract and spinal cord following noxious gastric distention in the rat. Neuroscience 1996; 74:873-84. [PMID: 8884783 DOI: 10.1016/0306-4522(96)00173-x] [Citation(s) in RCA: 130] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
c-Fos has been used as a marker for activity in the spinal cord following noxious somatic or visceral stimulation. Although the viscera receive dual afferent innervation, distention of hollow organs (i.e. esophagus, stomach, descending colon and rectum) induces significantly more c-Fos in second order neurons in the nucleus of the solitary tract and lumbosacral spinal cord, which receive parasympathetic afferent input (vagus, pelvic nerves), than the thoracolumbar spinal cord, which receives sympathetic afferent input (splanchnic nerves). The purpose of this study was to determine the contribution of sympathetic and parasympathetic afferent input to c-Fos expression in the nucleus of the solitary tract and spinal cord, and the influence of supraspinal pathways on Fos induction in the thoracolumbar spinal cord. Noxious gastric distention to 80 mmHg (gastric distension/80) was produced by repetitive inflation of a chronically implanted gastric balloon. Gastric distension/80 induced c-Fos throughout the nucleus of the solitary tract, with the densest labeling observed within 300 microns of the rostral pole of the area postrema. This area was analysed quantitatively following several manipulations. Gastric distension/80 induced a mean of 724 c-Fos-immunoreactive nuclei per section. Following subdiaphragmatic vagotomy plus distention (vagotomy/80), the induction of c-Fos-immunoreactive nuclei was reduced to 293 per section, while spinal transection at T2 plus distention (spinal transection/80) induced a mean of 581 nuclei per nucleus of the solitary tract section. Gastric distension/80 and vagotomy/80 induced minimal c-Fos in the T8-T10 spinal cord (50 nuclei/section), but spinal transection/80 induced 200 nuclei per section. Repetitive bolus injections of norepinephrine produced transient pressor responses mimicking the pressor response produced by gastric distension/80. This manipulation induced minimal c-Fos in the nucleus of the solitary tract and none in the spinal cord. It is concluded that noxious visceral input via parasympathetic vagal afferents, and to a lesser extent sympathetic afferents and the spinosolitary tract, contribute to gastric distention-induced c-Fos in the nucleus of the solitary tract. The induction of c-Fos in the nucleus of the solitary tract is significantly greater than in the viscerotopic segments of the spinal cord, which is partially under tonic descending inhibition, but is not subject to modulation by vagal gastric afferents. Distention pressures produced by noxious gastric distention are much greater than those produced during feeding, suggesting that c-Fos induction in the nucleus of the solitary tract to noxious distention is not associated with physiological mechanisms of feeding and satiety. The large vagal nerve-mediated induction of c-Fos in the nucleus of the solitary tract following gastric distension suggests that parasympathetic afferents contribute to the processing of noxious visceral stimuli, perhaps by contributing to the affective-emotional component of visceral pain.
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Affiliation(s)
- R J Traub
- Department of Pharmacology, University of Iowa College of Medicine, Iowa City 52242, USA
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23
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Schuligoi R, Herzeg G, Wachter C, Jocic M, Holzer P. Differential expression of c-fos messenger RNA in the rat spinal cord after mucosal and serosal irritation of the stomach. Neuroscience 1996; 72:535-44. [PMID: 8737422 DOI: 10.1016/0306-4522(95)00552-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Expression of the immediate early gene c-fos is considered to be a marker for neuronal activation in the spinal cord in response to afferent input. Since the stomach is continually exposed to injurious chemicals, the present study examined whether application of acid (0.15 M HCl) and formalin (5%) to the gastric mucosa or serosal surface of the stomach stimulates c-fos transcription in the caudal thoracic spinal cord of anaesthetized rats. The spinal cord was removed 15, 45 or 120 min after exposure of the stomach to the noxious chemicals and processed for quantitative in situ hybridization autoradiography of c-fos messenger RNA. Exposure of the gastric mucosa to acid or formalin failed to increase the expression of c-fos messenger RNA in the thoracic spinal cord. Application of acid to the serosal surface of the stomach was also unable to stimulate c-fos transcription, whereas serosal application of formalin led to substantial expression of c-fos messenger RNA in the superficial but also deeper laminae of the spinal dorsal horn when examined 45 min, but not 15 or 120 min, post-stimulation. The highest expression of c-fos messenger RNA was seen when formalin was injected subcutaneously into one hindpaw and c-fos transcription was examined in the lumbar spinal cord. These data indicate that acute exposure of the gastric mucosa to chemical injury does not provide the afferent input which is necessary to cause appreciable c-fos transcription in second order neurons within the spinal cord. Stimulation of the gastric mucosa by acid and formalin was followed, however, by gastric hyperaemia in which spinal afferents releasing vasodilator peptides have been implicated. It is concluded, therefore, that acute stimulation of nociceptive afferents in the stomach causes local homoeostatic reactions but does not necessarily provide afferent input sufficient to recruit spinal nociceptive circuits.
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Affiliation(s)
- R Schuligoi
- Department of Experimental and Clinical Pharmacology, University of Graz, Austria
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24
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Khurana RK, Petras JM. Sensory innervation of the canine esophagus, stomach, and duodenum. THE AMERICAN JOURNAL OF ANATOMY 1991; 192:293-306. [PMID: 1759692 DOI: 10.1002/aja.1001920309] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The sensory innervation of the postpharyngeal foregut was investigated by injecting the enzyme horseradish peroxidase (HRP) into the walls of the esophagus, stomach, or duodenum. The transported HRP was identified histochemically, labeled neurons in the spinal and vagal ganglia were counted, and the results were plotted using an SAS statistical program. The spinal sensory fields of each viscus were defined using three determinations: craniocaudal extent, principal innervation field, and peak innervation field. The data revealed that innervation fields are craniocaudally extensive, the sensory field of each viscus overlaps significantly with its neighbor, yet each viscus can be characterized by a field of peak innervation density. Craniocaudal innervation of the esophagus spans as many as 22-23 paired spinal ganglia (C1-L2). There are two peak innervation fields for the cervical (C2-C6 and T2-T4) and for the thoracic (T2-T4 and T8-T12) sectors of the esophagus. The sensory innervation of the stomach extends craniocaudally over as many as 25 paired spinal ganglia (C2-L5). The peak innervation field of the stomach spans a large area comprising the cranial, middle, and the immediately adjoining caudal thoracic ganglia (T2-T10). The duodenum is innervated craniocaudally by as many as 15 paired thoracolumbar ganglia (T2-L3). Peak innervation originates in the middle and caudal thoracic ganglia and cranial lumbar (T6-L1) ganglia. There is a recognizable viscerotopic organization in the sensory innervation of the postpharyngeal foregut; successively more caudal sectors of this region of the alimentary canal are supplied with sensory fibers from successively more caudal spinal dorsal root ganglia. Vagal afferent innervation of the esophagus, stomach, and duodenum is bilateral and originates predominantly, but not exclusively, from vast numbers of neurons in the nodose (distal) ganglia. The esophagus is innervated bilaterally and more abundantly by jugular (proximal) ganglia neurons than is either the stomach or duodenum. The physiological significance of the findings are discussed in relation to the phenomena of visceral pain and referred pain.
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Affiliation(s)
- R K Khurana
- Department of Neurology, University of Maryland School of Medicine, Baltimore 21201
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25
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Abstract
This paper reviews clinical and basic science research reports and is directed toward an understanding of visceral pain, with emphasis on studies related to spinal processing. Four main types of visceral stimuli have been employed in experimental studies of visceral nociception: (1) electrical, (2) mechanical, (3) ischemic, and (4) chemical. Studies of visceral pain are discussed in relation to the use and 'adequacy' of these stimuli and the responses produced (e.g., behavioral, pseudoaffective, neuronal, etc.). We propose a definition of an adequate noxious visceral stimulus and speculate on spinal mechanisms of visceral pain.
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Affiliation(s)
- T J Ness
- Department of Anesthesia, College of Medicine, University of Iowa, Iowa City, IA 52242, U.S.A. Department of Pharmacology, College of Medicine, University of Iowa, Iowa City, IA 52242, U.S.A
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26
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Yang H, Cuttitta F, Raybould H, Taché Y. Intrathecal injection of bombesin inhibits gastric acid secretion in the rat. Gastroenterology 1989; 96:1403-9. [PMID: 2714571 DOI: 10.1016/0016-5085(89)90505-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Bombesin (100-500 ng) injected intrathecally (T9-10) inhibited gastric acid secretion stimulated by pentagastrin and the GABAB agonist baclofen in urethane-anesthetized rats and basal gastric acid secretion in conscious, pylorus-ligated rats. Peptide action was dose-related, occurred within 30 min, and lasted for greater than 1 h. Bombesin-induced inhibition of pentagastrin-stimulated gastric acid secretion was not altered by cervical cord transection. Intravenous infusion of the monoclonal bombesin antibody 2A11 abolished intravenous bombesin (10 micrograms/kg.h)-induced 33% inhibition of gastric response to pentagastrin but did not alter intrathecal bombesin (200 ng)-induced 38% inhibition of gastric response to pentagastrin. The inhibitory effect of bombesin (200 ng) on pentagastrin-stimulated gastric secretion was reversed by bilateral adrenalectomy or removal of celiac and mesenteric ganglia. Intrathecal injections of rat calcitonin gene-related peptide, neuromedin B, neuromedin U, and the stable substance P analogue (pGlu5, MePhe8, MeGly9)-substance P(5-11) did not alter pentagastrin-stimulated gastric acid secretion. These results demonstrate that bombesin injected into the subarachnoid space of the spinal cord inhibits vagally stimulated and pentagastrin-stimulated gastric secretion in rats. Bombesin action is peptide specific, exerted at a spinal site, and expressed through the sympathetic nervous system.
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Affiliation(s)
- H Yang
- Center for Ulcer Research and Education, Veterans Administration Medical Center, Los Angeles, California
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27
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Peyronnard JM, Charron L, Lavoie J, Messier JP, Dubreuil M. Carbonic anhydrase and horseradish peroxidase: double labelling of rat dorsal root ganglion neurons innervating motor and sensory peripheral nerves. ANATOMY AND EMBRYOLOGY 1988; 177:353-9. [PMID: 2451452 DOI: 10.1007/bf00315844] [Citation(s) in RCA: 34] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Dorsal root ganglion neurons supplying peroneus longus, soleus and gastrocnemius medius muscles and the sural nerve of the rat were labelled with horseradish peroxidase and analysed for their carbonic anhydrase content. Staining of the sections was done either on the same or on alternate slides. Both methods led to the same results, despite a slight fading of the carbonic anhydrase reaction in double-stained sections. The data indicated that the muscles under study were supplied by approximately the same number of horseradish peroxidase-labelled cells, irrespective of their differences in size. 74.9% of these labelled neurons had diameters exceeding 30 microns and 52.4% of them also stained for carbonic anhydrase. The double-labelled cells represented 66.9% of the population of large neurons (greater than 30 microns) and comprised most of those measuring over 47.5 microns. Richness in carbonic anhydrase of the large muscle afferent neurons may be linked to their innervation of the stretch receptors, as components of an active apparatus which includes the gamma motor axons which also stain positively for carbonic anhydrase. In contrast, the ganglion cells supplying the sural nerve were almost totally devoid of carbonic anhydrase, as only 6.4% showed double labelling. This contingent possibly represents the muscle afferents of the small motoneural population which supplies, through this nerve, part of the foot musculature of the rat.
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Affiliation(s)
- J M Peyronnard
- Centre de recherche en sciences neurologiques, Université de Montréal, Quebec, Canada
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28
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Rinaman L, Miselis RR. The organization of vagal innervation of rat pancreas using cholera toxin-horseradish peroxidase conjugate. JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM 1987; 21:109-25. [PMID: 3450690 DOI: 10.1016/0165-1838(87)90014-2] [Citation(s) in RCA: 65] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
The present study was initiated to address the current controversy concerning the parasympathetic innervation of the pancreas, using a more sensitive tracer. The location of retrogradely labeled neurons within the dorsal motor nucleus of the vagus (DMV) was examined 48 h following injections of cholera toxin-horseradish peroxidase (CT-HRP) into designated areas of the rat pancreas. The brainstem and spinal cord were searched for any additional labeled neurons located outside of the DMV. Separate groups of animals were used for control injections into the adipose tissue of the greater omentum, the spleen, abdominal musculature, and the diaphragm. In addition, CT-HRP was dripped over the surfaces of the abdominal viscera in another group of animals. These control cases were designed to indicate whether diffusion of the neural tracer away from injection sites had occurred and had resulted in labeling of neurons which did not innervate the injected areas. Following injection of CT-HRP into the right lobe of the pancreas, labeled neurons were found primarily within the medial region of the left DMV. Injection of CT-HRP into the left lobe of the pancreas resulted in retrogradely labeled neurons predominantly within the medial region of the right DMV. Following injections into the entire pancreas, neural labeling was seen bilaterally within the DMV and was concentrated within the medial regions, with a slightly higher degree of labeling within the right DMV. No labeled neurons were seen within the nucleus ambiguus or other areas of the brainstem or spinal cord following pancreatic injections. Furthermore, no afferent labeling within the nucleus of the solitary tract (NTS) was observed, although a very small number of neurons within the nodose ganglia were labeled. The dendrites of backfilled DMV neurons could be seen extending across the midline to the contralateral DMV as well as dorsally into certain subnuclei of the NTS, and to the borders of the area postrema and the fourth ventricle. These results indicate that both the motor and sensory innervation of the rat pancreas are more restricted than has been previously suggested.
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Affiliation(s)
- L Rinaman
- School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104
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29
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Neuhuber WL, Sandoz PA, Fryscak T. The central projections of primary afferent neurons of greater splanchnic and intercostal nerves in the rat. A horseradish peroxidase study. ANATOMY AND EMBRYOLOGY 1986; 174:123-44. [PMID: 3706772 DOI: 10.1007/bf00318344] [Citation(s) in RCA: 95] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
The central projections of primary afferent fibers of the greater splanchnic nerve of the rat were investigated using the transganglionic horseradish peroxidase transport technique. In addition, the corresponding spinal ganglion cells and the preganglionic sympathetic neurons were demonstrated. For comparing visceral and somatic afferents, intercostal nerve afferents were labelled by the same technique. Splanchnic afferent dorsal root ganglion cells were found at segments T3 to T13 ipsilaterally, with the greatest density at T8 to T12. Labelled cells represented about 10%-15% of all neurons in the ganglia at maximal projection levels. They were randomly distributed within individual ganglia. The great majority were medium to small sized and round to slightly oval in shape. In the spinal cord, labelled visceral afferent axons were found maximally at T8 to T11, but could be detected in decreasing density up to T1 and down to L1. They were distributed over Lissauer's tract and the dorsal funiculus to a medial and lateral collateral pathway (MCP and LCP, respectively). The MCP, somewhat more prominent than the LCP, was destined primarily to clustered presumptive terminal fields in medial lamina I and outermost lamina IIa. Only a few axons continued further to laminae V and X. Splanchnic afferent axons, most likely derived from the MCP, formed a longitudinal bundle ventral to the central canal. The LCP consisted of more or less well-defined axon bundles emanating from the lateral Lissauer's tract and curving round the lateral edge of the dorsal horn and through the dorsolateral funiculus. Presumptive terminal sites of LCP axons are the lateral laminae I and IIa, the nucleus of the dorsolateral funiculus and the dorsal part of lamina V. A few LCP axons were seen in the vicinity of lateral dendrites of preganglionic sympathetic axons. Visceroafferent terminals were absent from laminae IIb-IV and VII. The possible consequences of the MCP/LCP duality for the central connections of splanchnic afferents are discussed. Some splanchnic afferents ascended to the gracile and cuneate nuclei, and rarely to the spinal trigeminal nucleus. These results fit into the general concept of visceroafferent terminal organization that has emerged during the last few years. Differences to other reports in the detailed arrangement of fibers and terminals are discussed. Somatoafferent cell bodies represented the vast majority of neurons in the respective spinal ganglia. Cell sizes encompassed the whole range from very small to very large without a clear predominance of one particular size class.(ABSTRACT TRUNCATED AT 400 WORDS)
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30
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Abstract
Systemically administered bombesin reduces food intake in rats, mice, baboons, and humans. The mechanism of action is unknown. We report here that presumed neural disconnection of the gastrointestinal tract from the brain blocked the reduction of food intake by exogenous bombesin at a test meal in rats. We also found that bombesin increased the postprandial intermeal interval, and that this effect was not blocked by neural disconnection.
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31
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Torigoe Y, Cernucan RD, Nishimoto JA, Blanks RH. Sympathetic preganglionic efferent and afferent neurons mediated by the greater splanchnic nerve in rabbit. Exp Neurol 1985; 87:334-48. [PMID: 3967718 DOI: 10.1016/0014-4886(85)90224-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Motion sickness, a multisymptom disorder characterized by abnormal gastrointestinal motility and emesis, can be induced by vestibular effects on the sympathetic portion of the autonomic nervous system. However, the vestibular-autonomic pathways are unknown. As a first step in the analysis, we identified the locus of preganglionic sympathetic neurons (PSNs) and dorsal root afferent ganglionic neurons (DRGs) which supply sympathetic innervation to major portions of the gastrointestinal tract in the rabbit. Retrograde labeling of neurons was obtained by application of horseradish peroxidase (HRP) to the cut end of the greater splanchnic nerve. Labeled PSNs were found, ipsilaterally, within the T1 to T11 spinal cord segments, with the highest density of neurons in T6. Most PSNs were located within the intermediolateral column (IML), but a significant portion also occurred within the lateral funiculus (LF), the intercalated region (IC) and the central autonomic area (CA). The proportion of labeling between the four regions depended on the spinal cord segment. In the midthoracic levels, the distribution of labeled neurons was denser in the IML and LF, and in the caudal thoracic segments, the majority were localized in the IC and CA. Labeled cells in these four areas varied morphologically from large fusiform neurons in the IC to small fusiform neurons in the LF, small stellate neurons in the CA, and medium-size stellate neurons in the IML. The DRGs were labeled in thoracic segments T1 to T12, with the majority between T5 and T11. These labeled DRG somata of the greater splanchnic nerve were smaller in comparison with unlabeled ones.
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Kausz M, Réthelyi M. Lamellar arrangement of neuronal somata in the dorsal root ganglion of the cat. SOMATOSENSORY RESEARCH 1985; 2:193-204. [PMID: 4001674 DOI: 10.3109/07367228509144563] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The retrograde transport of horseradish peroxidase (HRP) was used to study the distribution of perikarya in the dorsal root ganglia (DRGs). Injections of HRP subcutaneously into a small area of the foreleg, flank, perineum, the central pad of the forepaw, muscles of the foreleg, the wall of the urinary bladder, and mucosa of the rectum resulted in many retrogradely labeled perikarya in one DRG. Labeled perikarya were distributed in the ganglia proximally to distal elongated slabs or columns, especially in cases of subcutaneous injections. A similar slab, or columnar distribution, of HRP-labeled perikarya was noticed when the tracer was injected into the spinal cord preceded by the transection of all dorsal root filaments but one. Perikarya located along the lateral border of the ganglion were labeled through rostral filaments, and perikarya distributed along the medial border were labeled through caudal filaments. A segmental somatotopic map has been conceived for the DRG as an intermediate territory between the periphery and the spinal cord.
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Fryscak T, Zenker W, Kantner D. Afferent and efferent innervation of the rat esophagus. A tracing study with horseradish peroxidase and nuclear yellow. ANATOMY AND EMBRYOLOGY 1984; 170:63-70. [PMID: 6089609 DOI: 10.1007/bf00319459] [Citation(s) in RCA: 54] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
The technique of retrograde labeling of nerve cells with HRP and nuclear yellow as well as transganglionic anterograde HRP-tracing of sensory projections into the CNS were used to establish the motor and sensory innervation pattern of two parts of the rat esophagus: the cervical and the abdominal segment. For comparison, also the innervation of the anterior wall of the stomach was studied. Application of HRP to the cervical part of the esophagus resulted in bilateral labeling of neurons in the nucleus ambiguus exclusively, while application of the tracer to the abdominal part was followed by labeling of cells in both the nucleus ambiguus and the dorsal motor nucleus of the vagus. Application of tracer to the wall of the stomach caused labeling of cells in the dorsal motor nucleus of the vagus exclusively. Labeling appeared always bilaterally. In all experiments there was a profuse labeling of primary afferent neurons with cell bodies in both nodose ganglia and endings in certain subnuclei of the solitary nucleus. Endings related to the cervical esophagus projected into the ventral subnuclei, projections from the abdominal esophagus were located in the ventral and medial subnuclei, those from the stomach in the medial subnucleus solely. The area postrema and the commissural nucleus received afferents from both organs, the esophagus and the stomach. Double labeling experiments with HRP and nuclear yellow provided no signs of overlap of sensory innervation areas of the sites investigated in this study. Within the wall of the esophagus no labeled intramural cells nor nerve fibers were found in sections beyond the injection sites.
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Clerc N. Afferent innervation of the lower oesophageal sphincter of the cat. An HRP study. JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM 1983; 9:623-36. [PMID: 6672050 DOI: 10.1016/0165-1838(83)90118-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Labeling of afferent neurons by the retrograde axonal transport of horseradish peroxidase (HRP) was performed on anaesthetized cats in order to examine the afferent innervation of the lower oesophageal sphincter (LOS), involving both the vagal and the sympathetic nerves. The labeled cells, whose fibres follow the sympathetic pathways were found in dorsal root ganglia from T1 to L2. Nerve section experiments indicated that the main pathways involved were the splanchnic nerves, as expected from classical data. Additional pathways passing through the sympathetic cardiac branch emerging from the stellate ganglion and the thoracic sympathetic branches were also evidenced. This work corroborated the electrophysiological data showing the richness of the LOS sensory vagal innervation. Nevertheless, in this case the difficulties related to the HRP technique are particularly enhanced since the abdominal sensory vagal fibres can be affected by HRP injections.
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Li GQ, Fan YH, Wang JB. Tracing the origin of the sympathetic afferent nerve of the ventriculus cordis by means of horseradish peroxidase method in the rat. ACTA ACADEMIAE MEDICINAE WUHAN = WU-HAN I HSUEH YUAN HSUEH PAO 1983; 3:147-52. [PMID: 6621969 DOI: 10.1007/bf02856648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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Lorenz DN, Ellis SB, Epstein AN. Differential effects of upper gastrointestinal fill on milk ingestion and nipple attachment in the suckling rat. Dev Psychobiol 1982; 15:309-30. [PMID: 7201938 DOI: 10.1002/dev.420150404] [Citation(s) in RCA: 33] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Milk intake and nipple attachment behaviors were studied in the natural suckling situation after gastrointestinal preloading. Rat pups, deprived of their dam for 9 hr at 1, 10, or 20 days of age, were preloaded by gavage with volumes ranging from 2 to 16% of their body weight and returned to suckle. Preloads of artificial bitch's milk decreased the intake of mother's milk in a volume-related manner at all ages. At 1 and 10 days 4% preloads decreased milk intake without affecting attachment behaviors; larger preloads of 8 and 16% decreased intake and reduced the incidence of attachment. At 20 days of age small and large preloads decreased both incidence of attachment and milk intake. Preloads up to 8% of body weight had no effect on latency to attach at any age. Complete subdiaphragmatic bilateral vagotomy increased milk intake of 7-9 day-old pups fed automatically through an anterior mouth cannula in a nonsuckling situation. Vagotomy combined with spinal cordotomy (T2-T3) resulted in a synergistic hyperphagia and massive distension of the upper GI tract. The results indicate that suckling rats can control their intake of mother's milk while remaining attached to a nipple as early as 1 day of age. The suppression of ingestion in response to GI filling appears to be mediated by visceral afferent activity. Conversely, attachment behaviors are less affected by GI fill. This suggests that ingestive behaviors and attachment behaviors have different controls during the 1st 10 days of postnatal development.
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Janjua MZ, Leong SK. Labelling of cervical and thoracic spinal neurones following injection of horseradish peroxidase in the leg muscles of rats. Brain Res 1981; 223:386-90. [PMID: 6169407 DOI: 10.1016/0006-8993(81)91152-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Following injection of horseradish peroxidase (HRP) solution in the gastrocnemius muscle or the extensor digitorum longus muscle in neonatal and developing albino rats, some neurones in the cervical enlargement, mid-thoracic region and sacral region were labelled in addition to the region of the spinal cord from where the sciatic nerves emerged. The labelling was most probably the result of diffusion of HRP solution from the site of injection to nearby structures.
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Yu WH. Uptake sites of horseradish peroxidase after injection into peritoneal structures: defining some pitfalls. J Neurosci Methods 1980; 2:123-33. [PMID: 7392667 DOI: 10.1016/0165-0270(80)90054-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Following injection of horseradish peroxidase (HRP) either into the jejunal wall or the peritoneal cavity, neurons in the dorsal motor nucleus of the vagus nerve, celiac, nodose and spinal ganglia, and ventral and lateral horns of the spinal cord from the mid-thoracic to lumbar segments were labeled. When HRP was injected into the wall of the exteriorized gut, neurons of the spinal cord were not labeled. Furthermore, there was a significant decrease in the number of labeled neurons in the dorsal motor nucleus and ganglia examined. These results indicate that HRP injected into the intestinal wall could leak into the peritoneal cavity and be taken up and transported to neuronal cell bodies by nerve fibers not terminating in the injection area. The leakage of HRP to nearby abdominal structures and its subsequent uptake by nerve fibers is attributed to the lack of a diffusion barrier across the surfaces of the intestinal wall and the abdominal structures. It is suggested that in applying the HRP techniques for the study of neuronal connections in the peripheral nervous system, it is essential that carefully pla-ned control experiments be undertaken which can overcome the problem of mislabeling due to diffusion from the injection site.
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Noden DM. Somatotopic and functional organization of the avian trigeminal ganglion: an HRP analysis in the hatchling chick. J Comp Neurol 1980; 190:405-28. [PMID: 6967074 DOI: 10.1002/cne.901900302] [Citation(s) in RCA: 50] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
While the somatotopic organization of many central systems is well characterized, that of peripheral sensory neurons has not been adequately defined. This is especially true for the trigeminal ganglion. By applying HRP subcutaneously at each of 14 sites and also intramuscularly, it is possible to determine whether the location of sensory neurons within the ganglion reflects their peripheral projections. There is no discernible somatotopic organization of neurons in the ophthalmic lobe. However, the location of maxillary neurons in the maxillo-mandibular lobe is organized with the most posterior cells projecting to sites closest to the ganglion and with neurons located more anteriorly projecting to progressively more distant sites. There is a less well defined organization in the superior-inferior axis of the ganglion, and none along its proximal (root) to distal axis. Mandibular exteroceptive neurons are found primarily in the anterior region of the maxillo-mandibular lobe, while mandibular proprioceptive cells are located in the proximo-central part of this lobe. In most cases there is a considerable scattering of horseradish peroxidase (HRP)-filled neurons. Projections to contralateral ganglia, the trigeminal motor nucleus, and the trigeminal mesencephalic nucleus were also examined. Cytologically, the hatchling trigeminal consists of two interspersed types of neurons: large, lightly staining and smaller, darkly staining cells. Previous experiments have proved that these two cell types do not correspond to each of the embryonic precursors of trigeminal neurons, the neural crest and placodal cells. In this study HRP was found localized in both classes of neurons following injection at all sites, including jaw-closing muscles. This indicates that the dual cytology is not correlated with either distribution of peripheral fibers or exteroceptive vs. proprioceptive functions. The possibilities that the two types of neurons may have different central projections and/or may be related to visceral vs. somatic afferent functions are discussed.
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