Upregulation of the high-affinity choline transporter in colon relieves stress-induced hyperalgesia
Meng-Juan Lin,1,2 Bao-Ping Yu1,2 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; 2Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, Hubei, China Background: Irritable bowel syndrome (IBS) is a common...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2018-09-01
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| Series: | Journal of Pain Research |
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| Online Access: | https://www.dovepress.com/upregulation-of-the-high-affinity-choline-transporter-in-colon-relieve-peer-reviewed-article-JPR |
| _version_ | 1819078080883326976 |
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| author | Lin MJ Yu BP |
| author_facet | Lin MJ Yu BP |
| author_sort | Lin MJ |
| collection | DOAJ |
| description | Meng-Juan Lin,1,2 Bao-Ping Yu1,2 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; 2Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, Hubei, China Background: Irritable bowel syndrome (IBS) is a common disease with hyperalgesia, the mechanisms of which remain elusive. The cholinergic system is known to be involved in pain inhibitory pathways in multiple diseases, and its involvement in IBS is unknown.Objective: We aimed to determine whether high-affinity choline transporter CHT1, a major determinant of the cholinergic signaling capacity, is involved in regulating intestinal sensations associated with stress-induced visceral pain.Materials and methods: An IBS rat model was established by chronic water avoidance stress (WAS). Colonic pathologic alterations were detected by H&E staining. Visceral sensations were determined by scoring the abdominal withdrawal reflex (AWR) and visceromotor response (VMR) magnitude of the electromyogram in response to colorectal distension (CRD). Abdominal mechanical hyperalgesia was assessed by counting the number of withdrawal events evoked by applying von Frey filaments. Real-time PCR, Western blot, and immunostaining were performed to identify CHT1 expression in the colon. Acetylcholine (ACh) secretion was determined by ELISA. Effects of MKC-231, a choline uptake enhancer, on visceral pain were examined.Results: After 10 days of WAS exposure, AWR score and VMR magnitude in response to CRD were significantly enhanced and the number of withdrawal events was elevated. Protein and mRNA levels of CHT1 were considerably increased in the colon after WAS. CHT1 upregulation in the WAS-exposed group was largely abolished by ammonium pyrrolidinedithiocarbamate. The density of CHT1-positive intramuscular cells and enteric neurons in the myenteric plexus was enhanced in WAS-exposed rats. Pharmacologic enhancement of CHT1 activity by MKC-231 gavage could relieve the visceral pain of WAS rats by upregulating CHT1 protein expression and enhancing ACh production.Conclusion: CHT1 may exert an antinociceptive effect in stress-induced visceral pain by modulating ACh synthesis through nuclear factor kappa B signaling. MKC-231 could be used as a potential drug to treat disorders with hyperalgesia. Keywords: irritable bowel syndrome, high-affinity choline transporter, myenteric plexus, visceral hyperalgesia |
| first_indexed | 2024-12-21T19:07:25Z |
| format | Article |
| id | doaj.art-872445c19abe414f93b286ca1bf50f54 |
| institution | Directory Open Access Journal |
| issn | 1178-7090 |
| language | English |
| last_indexed | 2024-12-21T19:07:25Z |
| publishDate | 2018-09-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Pain Research |
| spelling | doaj.art-872445c19abe414f93b286ca1bf50f542022-12-21T18:53:17ZengDove Medical PressJournal of Pain Research1178-70902018-09-01Volume 111971198240787Upregulation of the high-affinity choline transporter in colon relieves stress-induced hyperalgesiaLin MJYu BPMeng-Juan Lin,1,2 Bao-Ping Yu1,2 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; 2Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, Hubei, China Background: Irritable bowel syndrome (IBS) is a common disease with hyperalgesia, the mechanisms of which remain elusive. The cholinergic system is known to be involved in pain inhibitory pathways in multiple diseases, and its involvement in IBS is unknown.Objective: We aimed to determine whether high-affinity choline transporter CHT1, a major determinant of the cholinergic signaling capacity, is involved in regulating intestinal sensations associated with stress-induced visceral pain.Materials and methods: An IBS rat model was established by chronic water avoidance stress (WAS). Colonic pathologic alterations were detected by H&E staining. Visceral sensations were determined by scoring the abdominal withdrawal reflex (AWR) and visceromotor response (VMR) magnitude of the electromyogram in response to colorectal distension (CRD). Abdominal mechanical hyperalgesia was assessed by counting the number of withdrawal events evoked by applying von Frey filaments. Real-time PCR, Western blot, and immunostaining were performed to identify CHT1 expression in the colon. Acetylcholine (ACh) secretion was determined by ELISA. Effects of MKC-231, a choline uptake enhancer, on visceral pain were examined.Results: After 10 days of WAS exposure, AWR score and VMR magnitude in response to CRD were significantly enhanced and the number of withdrawal events was elevated. Protein and mRNA levels of CHT1 were considerably increased in the colon after WAS. CHT1 upregulation in the WAS-exposed group was largely abolished by ammonium pyrrolidinedithiocarbamate. The density of CHT1-positive intramuscular cells and enteric neurons in the myenteric plexus was enhanced in WAS-exposed rats. Pharmacologic enhancement of CHT1 activity by MKC-231 gavage could relieve the visceral pain of WAS rats by upregulating CHT1 protein expression and enhancing ACh production.Conclusion: CHT1 may exert an antinociceptive effect in stress-induced visceral pain by modulating ACh synthesis through nuclear factor kappa B signaling. MKC-231 could be used as a potential drug to treat disorders with hyperalgesia. Keywords: irritable bowel syndrome, high-affinity choline transporter, myenteric plexus, visceral hyperalgesiahttps://www.dovepress.com/upregulation-of-the-high-affinity-choline-transporter-in-colon-relieve-peer-reviewed-article-JPRIrritable bowel syndromehigh affinity choline transportermyenteric plexusvisceral hyperalgesia |
| spellingShingle | Lin MJ Yu BP Upregulation of the high-affinity choline transporter in colon relieves stress-induced hyperalgesia Journal of Pain Research Irritable bowel syndrome high affinity choline transporter myenteric plexus visceral hyperalgesia |
| title | Upregulation of the high-affinity choline transporter in colon relieves stress-induced hyperalgesia |
| title_full | Upregulation of the high-affinity choline transporter in colon relieves stress-induced hyperalgesia |
| title_fullStr | Upregulation of the high-affinity choline transporter in colon relieves stress-induced hyperalgesia |
| title_full_unstemmed | Upregulation of the high-affinity choline transporter in colon relieves stress-induced hyperalgesia |
| title_short | Upregulation of the high-affinity choline transporter in colon relieves stress-induced hyperalgesia |
| title_sort | upregulation of the high affinity choline transporter in colon relieves stress induced hyperalgesia |
| topic | Irritable bowel syndrome high affinity choline transporter myenteric plexus visceral hyperalgesia |
| url | https://www.dovepress.com/upregulation-of-the-high-affinity-choline-transporter-in-colon-relieve-peer-reviewed-article-JPR |
| work_keys_str_mv | AT linmj upregulationofthehighaffinitycholinetransporterincolonrelievesstressinducedhyperalgesia AT yubp upregulationofthehighaffinitycholinetransporterincolonrelievesstressinducedhyperalgesia |