Nucleus tractus solitarius mediates hyperalgesia induced by chronic pancreatitis in rats
©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved..
BACKGROUND: Central sensitization plays a pivotal role in the maintenance of chronic pain induced by chronic pancreatitis (CP). We hypothesized that the nucleus tractus solitarius (NTS), a primary central site that integrates pancreatic afferents apart from the thoracic spinal dorsal horn, plays a key role in the pathogenesis of visceral hypersensitivity in a rat model of CP.
AIM: To investigate the role of the NTS in the visceral hypersensitivity induced by chronic pancreatitis.
METHODS: CP was induced by the intraductal injection of trinitrobenzene sulfonic acid (TNBS) in rats. Pancreatic hyperalgesia was assessed by referred somatic pain via von Frey filament assay. Neural activation of the NTS was indicated by immunohistochemical staining for Fos. Basic synaptic transmission within the NTS was assessed by electrophysiological recordings. Expression of vesicular glutamate transporters (VGluTs), N-methyl-D-aspartate receptor subtype 2B (NR2B), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subtype 1 (GluR1) was analyzed by immunoblotting. Membrane insertion of NR2B and GluR1 was evaluated by electron microscopy. The regulatory role of the NTS in visceral hypersensitivity was detected via pharmacological approach and chemogenetics in CP rats.
RESULTS: TNBS treatment significantly increased the number of Fos-expressing neurons within the caudal NTS. The excitatory synaptic transmission was substantially potentiated within the caudal NTS in CP rats (frequency: 5.87 ± 1.12 Hz in CP rats vs 2.55 ± 0.44 Hz in sham rats, P < 0.01; amplitude: 19.60 ± 1.39 pA in CP rats vs 14.71 ± 1.07 pA in sham rats; P < 0.01). CP rats showed upregulated expression of VGluT2, and increased phosphorylation and postsynaptic trafficking of NR2B and GluR1 within the caudal NTS. Blocking excitatory synaptic transmission via the AMPAR antagonist CNQX and the NMDAR antagonist AP-5 microinjection reversed visceral hypersensitivity in CP rats (abdominal withdraw threshold: 7.00 ± 1.02 g in CNQX group, 8.00 ± 0.81 g in AP-5 group and 1.10 ± 0.27 g in saline group, P < 0.001). Inhibiting the excitability of NTS neurons via chemogenetics also significantly attenuated pancreatic hyperalgesia (abdominal withdraw threshold: 13.67 ± 2.55 g in Gi group, 2.00 ± 1.37 g in Gq group, and 2.36 ± 0.67 g in mCherry group, P < 0.01).
CONCLUSION: Our findings suggest that enhanced excitatory transmission within the caudal NTS contributes to pancreatic pain and emphasize the NTS as a pivotal hub for the processing of pancreatic afferents, which provide novel insights into the central sensitization of painful CP.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
World journal of gastroenterology - 25(2019), 40 vom: 28. Okt., Seite 6077-6093 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bai, Yang [VerfasserIn] |
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| Links: |
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| Themen: |
8T3HQG2ZC4 |
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| Anmerkungen: |
Date Completed 26.02.2020 Date Revised 26.02.2020 published: Print Citation Status MEDLINE |
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| doi: |
10.3748/wjg.v25.i40.6077 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM30291059X |
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| 100 | 1 | |a Bai, Yang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Nucleus tractus solitarius mediates hyperalgesia induced by chronic pancreatitis in rats |
| 264 | 1 | |c 2019 | |
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| 500 | |a Date Completed 26.02.2020 | ||
| 500 | |a Date Revised 26.02.2020 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Central sensitization plays a pivotal role in the maintenance of chronic pain induced by chronic pancreatitis (CP). We hypothesized that the nucleus tractus solitarius (NTS), a primary central site that integrates pancreatic afferents apart from the thoracic spinal dorsal horn, plays a key role in the pathogenesis of visceral hypersensitivity in a rat model of CP | ||
| 520 | |a AIM: To investigate the role of the NTS in the visceral hypersensitivity induced by chronic pancreatitis | ||
| 520 | |a METHODS: CP was induced by the intraductal injection of trinitrobenzene sulfonic acid (TNBS) in rats. Pancreatic hyperalgesia was assessed by referred somatic pain via von Frey filament assay. Neural activation of the NTS was indicated by immunohistochemical staining for Fos. Basic synaptic transmission within the NTS was assessed by electrophysiological recordings. Expression of vesicular glutamate transporters (VGluTs), N-methyl-D-aspartate receptor subtype 2B (NR2B), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subtype 1 (GluR1) was analyzed by immunoblotting. Membrane insertion of NR2B and GluR1 was evaluated by electron microscopy. The regulatory role of the NTS in visceral hypersensitivity was detected via pharmacological approach and chemogenetics in CP rats | ||
| 520 | |a RESULTS: TNBS treatment significantly increased the number of Fos-expressing neurons within the caudal NTS. The excitatory synaptic transmission was substantially potentiated within the caudal NTS in CP rats (frequency: 5.87 ± 1.12 Hz in CP rats vs 2.55 ± 0.44 Hz in sham rats, P < 0.01; amplitude: 19.60 ± 1.39 pA in CP rats vs 14.71 ± 1.07 pA in sham rats; P < 0.01). CP rats showed upregulated expression of VGluT2, and increased phosphorylation and postsynaptic trafficking of NR2B and GluR1 within the caudal NTS. Blocking excitatory synaptic transmission via the AMPAR antagonist CNQX and the NMDAR antagonist AP-5 microinjection reversed visceral hypersensitivity in CP rats (abdominal withdraw threshold: 7.00 ± 1.02 g in CNQX group, 8.00 ± 0.81 g in AP-5 group and 1.10 ± 0.27 g in saline group, P < 0.001). Inhibiting the excitability of NTS neurons via chemogenetics also significantly attenuated pancreatic hyperalgesia (abdominal withdraw threshold: 13.67 ± 2.55 g in Gi group, 2.00 ± 1.37 g in Gq group, and 2.36 ± 0.67 g in mCherry group, P < 0.01) | ||
| 520 | |a CONCLUSION: Our findings suggest that enhanced excitatory transmission within the caudal NTS contributes to pancreatic pain and emphasize the NTS as a pivotal hub for the processing of pancreatic afferents, which provide novel insights into the central sensitization of painful CP | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chronic pancreatitis | |
| 650 | 4 | |a Excitatory synaptic transmission | |
| 650 | 4 | |a Nucleus tractus solitarius | |
| 650 | 4 | |a Rat | |
| 650 | 4 | |a Visceral hypersensitivity | |
| 650 | 7 | |a Trinitrobenzenesulfonic Acid |2 NLM | |
| 650 | 7 | |a 8T3HQG2ZC4 |2 NLM | |
| 700 | 1 | |a Chen, Ying-Biao |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Xin-Tong |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yan-Bing |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Li-Tian |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ying-Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Hong-Ke |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Ming-Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Bo-Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yun-Qing |e verfasserin |4 aut | |
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