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Inhibition of the high affinity choline transporter enhances hyperalgesia in a rat model of chronic pancreatitis.
Biochem Biophys Res Commun. 2017 06 17; 488(1):204-210.BB

Abstract

BACKGROUND

The mechanisms underlying chronic and persistent pain associated with chronic pancreatitis (CP) are not completely understood. The cholinergic system is one of the major neural pathways of the pancreas. Meanwhile, this system plays an important role in chronic pain. We hypothesized that the high affinity choline transporter CHT1, which is a main determinant of cholinergic signaling capacity, is involved in regulating pain associated with CP.

METHODS

CP was induced by intraductal injection of 2% trinitrobenzene sulfonic acid (TNBS) in Sprague-Dawley rats. Pathological examination was used to evaluate the inflammation of pancreas and hyperalgesia was assessed by measuring the number of withdrawal events evoked by application of the von Frey filaments. CHT1 expression in pancreas-specific dorsal root ganglia (DRGs) was assessed through immunohistochemistry and western blotting. We also intraperitoneally injected the rats with hemicholinium-3 (HC-3, a specific inhibitor of CHT1). Then we observed its effects on the visceral hyperalgesia induced by CP, and on the acetylcholine (ACh) levels in the DRGs through using an acetylcholine/acetylcholinesterase assay kit.

RESULTS

Signs of CP were observed 21 days after TNBS injection. Rats subjected to TNBS infusions had increased sensitivity to mechanical stimulation of the abdomen. CHT1-immunoreactive cells were increased in the DRGs from rats with CP compared to naive or sham rats. Western blots indicated that CHT1 expression was significantly up-regulated in TNBS-treated rats when compared to naive or sham-operated rats at all time points following surgery. In the TNBS group, CHT1 expression was higher on day 28 than on day 7 or day 14, but there was no statistical difference in CHT1 expression on day 28 vs. day 21. Treatment with HC-3 (60 μg/kg, 80 μg/kg, or 100 μg/kg) markedly enhanced the mechanical hyperalgesia and reduced ACh levels in a dose-dependent manner in rats with CP.

CONCLUSION

We report for the first time that CHT1 may be involved in pain modulation in CP, as it plays an important role in pain inhibition. Increased CHT1 activity or the up-regulation of its expression may be used to treat pain in patients with CP.

Authors+Show Affiliations

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China; Key Laboratory of Hubei Province for Digestive System Diseases, Wuhan, China.Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China; Key Laboratory of Hubei Province for Digestive System Diseases, Wuhan, China.Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China; Key Laboratory of Hubei Province for Digestive System Diseases, Wuhan, China. Electronic address: yubaop62@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28483526

Citation

Luo, Dan, et al. "Inhibition of the High Affinity Choline Transporter Enhances Hyperalgesia in a Rat Model of Chronic Pancreatitis." Biochemical and Biophysical Research Communications, vol. 488, no. 1, 2017, pp. 204-210.
Luo D, Chen L, Yu B. Inhibition of the high affinity choline transporter enhances hyperalgesia in a rat model of chronic pancreatitis. Biochem Biophys Res Commun. 2017;488(1):204-210.
Luo, D., Chen, L., & Yu, B. (2017). Inhibition of the high affinity choline transporter enhances hyperalgesia in a rat model of chronic pancreatitis. Biochemical and Biophysical Research Communications, 488(1), 204-210. https://doi.org/10.1016/j.bbrc.2017.05.036
Luo D, Chen L, Yu B. Inhibition of the High Affinity Choline Transporter Enhances Hyperalgesia in a Rat Model of Chronic Pancreatitis. Biochem Biophys Res Commun. 2017 06 17;488(1):204-210. PubMed PMID: 28483526.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of the high affinity choline transporter enhances hyperalgesia in a rat model of chronic pancreatitis. AU - Luo,Dan, AU - Chen,Lei, AU - Yu,Baoping, Y1 - 2017/05/05/ PY - 2017/04/29/received PY - 2017/05/05/accepted PY - 2017/5/10/pubmed PY - 2017/9/22/medline PY - 2017/5/10/entrez KW - Acetylcholine KW - Chronic pancreatitis KW - High affinity choline transporter KW - Pain SP - 204 EP - 210 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 488 IS - 1 N2 - BACKGROUND: The mechanisms underlying chronic and persistent pain associated with chronic pancreatitis (CP) are not completely understood. The cholinergic system is one of the major neural pathways of the pancreas. Meanwhile, this system plays an important role in chronic pain. We hypothesized that the high affinity choline transporter CHT1, which is a main determinant of cholinergic signaling capacity, is involved in regulating pain associated with CP. METHODS: CP was induced by intraductal injection of 2% trinitrobenzene sulfonic acid (TNBS) in Sprague-Dawley rats. Pathological examination was used to evaluate the inflammation of pancreas and hyperalgesia was assessed by measuring the number of withdrawal events evoked by application of the von Frey filaments. CHT1 expression in pancreas-specific dorsal root ganglia (DRGs) was assessed through immunohistochemistry and western blotting. We also intraperitoneally injected the rats with hemicholinium-3 (HC-3, a specific inhibitor of CHT1). Then we observed its effects on the visceral hyperalgesia induced by CP, and on the acetylcholine (ACh) levels in the DRGs through using an acetylcholine/acetylcholinesterase assay kit. RESULTS: Signs of CP were observed 21 days after TNBS injection. Rats subjected to TNBS infusions had increased sensitivity to mechanical stimulation of the abdomen. CHT1-immunoreactive cells were increased in the DRGs from rats with CP compared to naive or sham rats. Western blots indicated that CHT1 expression was significantly up-regulated in TNBS-treated rats when compared to naive or sham-operated rats at all time points following surgery. In the TNBS group, CHT1 expression was higher on day 28 than on day 7 or day 14, but there was no statistical difference in CHT1 expression on day 28 vs. day 21. Treatment with HC-3 (60 μg/kg, 80 μg/kg, or 100 μg/kg) markedly enhanced the mechanical hyperalgesia and reduced ACh levels in a dose-dependent manner in rats with CP. CONCLUSION: We report for the first time that CHT1 may be involved in pain modulation in CP, as it plays an important role in pain inhibition. Increased CHT1 activity or the up-regulation of its expression may be used to treat pain in patients with CP. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/28483526/Inhibition_of_the_high_affinity_choline_transporter_enhances_hyperalgesia_in_a_rat_model_of_chronic_pancreatitis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(17)30895-1 DB - PRIME DP - Unbound Medicine ER -