Breakthrough Cancer Pain Is Associated with Spinal Gap Junction Activation via Regulation of Connexin 43 in a Mouse Model
Breakthrough cancer pain (BTcP) is a high-intensity, short-duration, unpredictable and uncontrollable pain. Recent studies have shown that activation of gap junction (GJ) in spinal cord plays an important role in the pathogenesis of BTcP. We examined the expressions of Glial fibrillary acidic protei...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-07-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fncel.2017.00207/full |
| _version_ | 1818230534063521792 |
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| author | Xin Li Siqing Jiang Hui Yang Qian Liao Shousong Cao Xuebin Yan Dong Huang |
| author_facet | Xin Li Siqing Jiang Hui Yang Qian Liao Shousong Cao Xuebin Yan Dong Huang |
| author_sort | Xin Li |
| collection | DOAJ |
| description | Breakthrough cancer pain (BTcP) is a high-intensity, short-duration, unpredictable and uncontrollable pain. Recent studies have shown that activation of gap junction (GJ) in spinal cord plays an important role in the pathogenesis of BTcP. We examined the expressions of Glial fibrillary acidic protein (GFAP), connexin (Cx) 43 protein and phosphorylation of Cx43 (p-Cx43) in the spinal cord of mice. In addition, we investigated the effects of Gap26, a selective GJ blocker, on the expressions of GFAP, Cx43 and p-Cx43 in BTcP mice. We found that the expressions of GFAP and Cx43 proteins were significantly upregulated while p-Cx43 was down-regulated in the spinal cord in a mouse model of BTcP. The overexpression of Cx43 protein in the spinal cord increased GJ formation and enhanced BTcP. The variation of the ratio of p-Cx43/T-Cx43 (total Cx43) affected the function of GJ to induce BTcP. Furthermore, BTcP was alleviated by Gap26 via reducing pain hypersensitivity. The inhibition of Cx43 and p-Cx43 by Gap26 attenuated BTcP but the p/T ratio of Cx43 remained unchanged in BTcP mice. We reveal that the expression and phosphorylation of Cx43 affected BTcP and GJ activation facilitated BTcP via a Cx43-mediated signaling in the spinal cord. The finding may provide a scientific rationale for discovery and development of novel therapeutic targets for the treatment of BTcP clinically. |
| first_indexed | 2024-12-12T10:36:01Z |
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| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-12T10:36:01Z |
| publishDate | 2017-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-6184e2d1dc404932ab2a91273ff290d12022-12-22T00:27:12ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022017-07-011110.3389/fncel.2017.00207262740Breakthrough Cancer Pain Is Associated with Spinal Gap Junction Activation via Regulation of Connexin 43 in a Mouse ModelXin Li0Siqing Jiang1Hui Yang2Qian Liao3Shousong Cao4Xuebin Yan5Dong Huang6Department of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, Central South UniversityChangsha, ChinaDepartment of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, Central South UniversityChangsha, ChinaDepartment of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, Central South UniversityChangsha, ChinaDepartment of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, Central South UniversityChangsha, ChinaDepartment of Pharmacology, School of Pharmacy, Southwest Medical UniversityLuzhou, ChinaDepartment of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, Central South UniversityChangsha, ChinaDepartment of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, Central South UniversityChangsha, ChinaBreakthrough cancer pain (BTcP) is a high-intensity, short-duration, unpredictable and uncontrollable pain. Recent studies have shown that activation of gap junction (GJ) in spinal cord plays an important role in the pathogenesis of BTcP. We examined the expressions of Glial fibrillary acidic protein (GFAP), connexin (Cx) 43 protein and phosphorylation of Cx43 (p-Cx43) in the spinal cord of mice. In addition, we investigated the effects of Gap26, a selective GJ blocker, on the expressions of GFAP, Cx43 and p-Cx43 in BTcP mice. We found that the expressions of GFAP and Cx43 proteins were significantly upregulated while p-Cx43 was down-regulated in the spinal cord in a mouse model of BTcP. The overexpression of Cx43 protein in the spinal cord increased GJ formation and enhanced BTcP. The variation of the ratio of p-Cx43/T-Cx43 (total Cx43) affected the function of GJ to induce BTcP. Furthermore, BTcP was alleviated by Gap26 via reducing pain hypersensitivity. The inhibition of Cx43 and p-Cx43 by Gap26 attenuated BTcP but the p/T ratio of Cx43 remained unchanged in BTcP mice. We reveal that the expression and phosphorylation of Cx43 affected BTcP and GJ activation facilitated BTcP via a Cx43-mediated signaling in the spinal cord. The finding may provide a scientific rationale for discovery and development of novel therapeutic targets for the treatment of BTcP clinically.http://journal.frontiersin.org/article/10.3389/fncel.2017.00207/fullbreakthrough cancer painspinal cordgap junctionconnexin 43phosphorylationGap26 |
| spellingShingle | Xin Li Siqing Jiang Hui Yang Qian Liao Shousong Cao Xuebin Yan Dong Huang Breakthrough Cancer Pain Is Associated with Spinal Gap Junction Activation via Regulation of Connexin 43 in a Mouse Model Frontiers in Cellular Neuroscience breakthrough cancer pain spinal cord gap junction connexin 43 phosphorylation Gap26 |
| title | Breakthrough Cancer Pain Is Associated with Spinal Gap Junction Activation via Regulation of Connexin 43 in a Mouse Model |
| title_full | Breakthrough Cancer Pain Is Associated with Spinal Gap Junction Activation via Regulation of Connexin 43 in a Mouse Model |
| title_fullStr | Breakthrough Cancer Pain Is Associated with Spinal Gap Junction Activation via Regulation of Connexin 43 in a Mouse Model |
| title_full_unstemmed | Breakthrough Cancer Pain Is Associated with Spinal Gap Junction Activation via Regulation of Connexin 43 in a Mouse Model |
| title_short | Breakthrough Cancer Pain Is Associated with Spinal Gap Junction Activation via Regulation of Connexin 43 in a Mouse Model |
| title_sort | breakthrough cancer pain is associated with spinal gap junction activation via regulation of connexin 43 in a mouse model |
| topic | breakthrough cancer pain spinal cord gap junction connexin 43 phosphorylation Gap26 |
| url | http://journal.frontiersin.org/article/10.3389/fncel.2017.00207/full |
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