Tags

Type your tag names separated by a space and hit enter

Nucleus tractus solitarius mediates hyperalgesia induced by chronic pancreatitis in rats.
World J Gastroenterol. 2019 Oct 28; 25(40):6077-6093.WJ

Abstract

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.

Authors+Show Affiliations

Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.Department of Anatomy, Fujian Health College, Fuzhou 350101, Fujian Province, China.Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.Department of Cardiology, The Second Affiliated Hospital of Xian Jiaotong University, Xian Jiaotong University, Xi'an 710004, Shaanxi Province, China.Department of Cardiology, The Second Affiliated Hospital of Xian Jiaotong University, Xian Jiaotong University, Xi'an 710004, Shaanxi Province, China.Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.Department of Cardiology, The Second Affiliated Hospital of Xian Jiaotong University, Xian Jiaotong University, Xi'an 710004, Shaanxi Province, China.Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31686764

Citation

Bai, Yang, et al. "Nucleus Tractus Solitarius Mediates Hyperalgesia Induced By Chronic Pancreatitis in Rats." World Journal of Gastroenterology, vol. 25, no. 40, 2019, pp. 6077-6093.
Bai Y, Chen YB, Qiu XT, et al. Nucleus tractus solitarius mediates hyperalgesia induced by chronic pancreatitis in rats. World J Gastroenterol. 2019;25(40):6077-6093.
Bai, Y., Chen, Y. B., Qiu, X. T., Chen, Y. B., Ma, L. T., Li, Y. Q., Sun, H. K., Zhang, M. M., Zhang, T., Chen, T., Fan, B. Y., Li, H., & Li, Y. Q. (2019). Nucleus tractus solitarius mediates hyperalgesia induced by chronic pancreatitis in rats. World Journal of Gastroenterology, 25(40), 6077-6093. https://doi.org/10.3748/wjg.v25.i40.6077
Bai Y, et al. Nucleus Tractus Solitarius Mediates Hyperalgesia Induced By Chronic Pancreatitis in Rats. World J Gastroenterol. 2019 Oct 28;25(40):6077-6093. PubMed PMID: 31686764.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nucleus tractus solitarius mediates hyperalgesia induced by chronic pancreatitis in rats. AU - Bai,Yang, AU - Chen,Ying-Biao, AU - Qiu,Xin-Tong, AU - Chen,Yan-Bing, AU - Ma,Li-Tian, AU - Li,Ying-Qi, AU - Sun,Hong-Ke, AU - Zhang,Ming-Ming, AU - Zhang,Ting, AU - Chen,Tao, AU - Fan,Bo-Yuan, AU - Li,Hui, AU - Li,Yun-Qing, PY - 2019/07/17/received PY - 2019/09/06/revised PY - 2019/09/11/accepted PY - 2019/11/6/entrez PY - 2019/11/7/pubmed PY - 2020/2/27/medline KW - Chronic pancreatitis KW - Excitatory synaptic transmission KW - Nucleus tractus solitarius KW - Rat KW - Visceral hypersensitivity SP - 6077 EP - 6093 JF - World journal of gastroenterology JO - World J Gastroenterol VL - 25 IS - 40 N2 - 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. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/31686764/Nucleus_tractus_solitarius_mediates_hyperalgesia_induced_by_chronic_pancreatitis_in_rats_ L2 - https://www.wjgnet.com/1007-9327/full/v25/i40/6077.htm DB - PRIME DP - Unbound Medicine ER -