Activation of GPR18 by Resolvin D2 Relieves Pain and Improves Bladder Function in Cyclophosphamide-Induced Cystitis Through Inhibiting TRPV1
Qudong Lu,1 Yang Yang,1 Hengshuai Zhang,1 Cheng Chen,2 Jiang Zhao,1 Zhenxing Yang,1 Yi Fan,1 Longkun Li,1 Huan Feng,1 Jingzhen Zhu,1 Shanhong Yi1 1Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, 400037, People’s Republic of China; 2Department of Burns, First Af...
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Dove Medical Press
2021
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oai:doaj.org-article:35e32d582eee4931a1db5519b345b2ee2021-11-16T18:47:50ZActivation of GPR18 by Resolvin D2 Relieves Pain and Improves Bladder Function in Cyclophosphamide-Induced Cystitis Through Inhibiting TRPV11177-8881https://doaj.org/article/35e32d582eee4931a1db5519b345b2ee2021-11-01T00:00:00Zhttps://www.dovepress.com/activation-of-gpr18-by-resolvin-d2-relieves-pain-and-improves-bladder--peer-reviewed-fulltext-article-DDDThttps://doaj.org/toc/1177-8881Qudong Lu,1 Yang Yang,1 Hengshuai Zhang,1 Cheng Chen,2 Jiang Zhao,1 Zhenxing Yang,1 Yi Fan,1 Longkun Li,1 Huan Feng,1 Jingzhen Zhu,1 Shanhong Yi1 1Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, 400037, People’s Republic of China; 2Department of Burns, First Affiliated Hospital, Army Medical University, Chongqing, 400037, People’s Republic of ChinaCorrespondence: Jingzhen Zhu; Shanhong YiDepartment of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, People’s Republic of ChinaTel +86 23-68774453Email zhujz1114@163.com; 2644057844@qq.comPurpose: Hyperalgesia and bladder overactivity are two main symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS). Cannabinoid receptors participate in the modulation of pain and bladder function. GPR18, a member of the cannabinoid receptor family, also participates in the regulation of pain and bladder function, but its underlying mechanisms are unknown. In this work, we sought to study the role of GPR18 in IC/BPS.Methods: A rat model of IC/BPS was established with cyclophosphamide (CYP). Paw withdrawal threshold (PWT) measurement and cystometry were used to evaluate pain and bladder function, respectively. RT-PCR, Western blotting and immunofluorescence were used to assess the expression and distribution of GPR18. The role of GPR18 in pain and bladder function was studied by intrathecal injection of resolvin D2 (RvD2, a GPR18 agonist) and O-1918 (a GPR18 antagonist). Calcium imaging was used to study the relationship between GPR18 and TRPV1.Results: A rat model of IC/BPS, which exhibited a decreased PWT and micturition interval, was successfully established with CYP. The mRNA and protein expression of GPR18 was reduced in the bladder and dorsal root ganglia (DRG) in rats with CYP-induced cystitis. Intrathecal injection of RvD2 increased the PWT and micturition interval. However, O-1918 blocked the therapeutic effect of RvD2. GPR18 was present in bladder afferent nerves and colocalized with TRPV1 in DRG, and RvD2 decreased capsaicin-induced calcium influx in DRG.Conclusion: Activation of GPR18 by RvD2 alleviated hyperalgesia and improved bladder function, possibly by inhibiting TRPV1 in rats with CYP-induced cystitis.Keywords: interstitial cystitis/bladder pain syndrome, GPR18, TRPV1, hyperalgesia, bladder overactivity, resolvin D2, O-1918Lu QYang YZhang HChen CZhao JYang ZFan YLi LFeng HZhu JYi SDove Medical Pressarticleinterstitial cystitis/bladder pain syndromegpr18trpv1hyperalgesiabladder overactivityresolvin d2o-1918Therapeutics. PharmacologyRM1-950ENDrug Design, Development and Therapy, Vol Volume 15, Pp 4687-4699 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
interstitial cystitis/bladder pain syndrome gpr18 trpv1 hyperalgesia bladder overactivity resolvin d2 o-1918 Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
interstitial cystitis/bladder pain syndrome gpr18 trpv1 hyperalgesia bladder overactivity resolvin d2 o-1918 Therapeutics. Pharmacology RM1-950 Lu Q Yang Y Zhang H Chen C Zhao J Yang Z Fan Y Li L Feng H Zhu J Yi S Activation of GPR18 by Resolvin D2 Relieves Pain and Improves Bladder Function in Cyclophosphamide-Induced Cystitis Through Inhibiting TRPV1 |
| description |
Qudong Lu,1 Yang Yang,1 Hengshuai Zhang,1 Cheng Chen,2 Jiang Zhao,1 Zhenxing Yang,1 Yi Fan,1 Longkun Li,1 Huan Feng,1 Jingzhen Zhu,1 Shanhong Yi1 1Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, 400037, People’s Republic of China; 2Department of Burns, First Affiliated Hospital, Army Medical University, Chongqing, 400037, People’s Republic of ChinaCorrespondence: Jingzhen Zhu; Shanhong YiDepartment of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, People’s Republic of ChinaTel +86 23-68774453Email zhujz1114@163.com; 2644057844@qq.comPurpose: Hyperalgesia and bladder overactivity are two main symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS). Cannabinoid receptors participate in the modulation of pain and bladder function. GPR18, a member of the cannabinoid receptor family, also participates in the regulation of pain and bladder function, but its underlying mechanisms are unknown. In this work, we sought to study the role of GPR18 in IC/BPS.Methods: A rat model of IC/BPS was established with cyclophosphamide (CYP). Paw withdrawal threshold (PWT) measurement and cystometry were used to evaluate pain and bladder function, respectively. RT-PCR, Western blotting and immunofluorescence were used to assess the expression and distribution of GPR18. The role of GPR18 in pain and bladder function was studied by intrathecal injection of resolvin D2 (RvD2, a GPR18 agonist) and O-1918 (a GPR18 antagonist). Calcium imaging was used to study the relationship between GPR18 and TRPV1.Results: A rat model of IC/BPS, which exhibited a decreased PWT and micturition interval, was successfully established with CYP. The mRNA and protein expression of GPR18 was reduced in the bladder and dorsal root ganglia (DRG) in rats with CYP-induced cystitis. Intrathecal injection of RvD2 increased the PWT and micturition interval. However, O-1918 blocked the therapeutic effect of RvD2. GPR18 was present in bladder afferent nerves and colocalized with TRPV1 in DRG, and RvD2 decreased capsaicin-induced calcium influx in DRG.Conclusion: Activation of GPR18 by RvD2 alleviated hyperalgesia and improved bladder function, possibly by inhibiting TRPV1 in rats with CYP-induced cystitis.Keywords: interstitial cystitis/bladder pain syndrome, GPR18, TRPV1, hyperalgesia, bladder overactivity, resolvin D2, O-1918 |
| format |
article |
| author |
Lu Q Yang Y Zhang H Chen C Zhao J Yang Z Fan Y Li L Feng H Zhu J Yi S |
| author_facet |
Lu Q Yang Y Zhang H Chen C Zhao J Yang Z Fan Y Li L Feng H Zhu J Yi S |
| author_sort |
Lu Q |
| title |
Activation of GPR18 by Resolvin D2 Relieves Pain and Improves Bladder Function in Cyclophosphamide-Induced Cystitis Through Inhibiting TRPV1 |
| title_short |
Activation of GPR18 by Resolvin D2 Relieves Pain and Improves Bladder Function in Cyclophosphamide-Induced Cystitis Through Inhibiting TRPV1 |
| title_full |
Activation of GPR18 by Resolvin D2 Relieves Pain and Improves Bladder Function in Cyclophosphamide-Induced Cystitis Through Inhibiting TRPV1 |
| title_fullStr |
Activation of GPR18 by Resolvin D2 Relieves Pain and Improves Bladder Function in Cyclophosphamide-Induced Cystitis Through Inhibiting TRPV1 |
| title_full_unstemmed |
Activation of GPR18 by Resolvin D2 Relieves Pain and Improves Bladder Function in Cyclophosphamide-Induced Cystitis Through Inhibiting TRPV1 |
| title_sort |
activation of gpr18 by resolvin d2 relieves pain and improves bladder function in cyclophosphamide-induced cystitis through inhibiting trpv1 |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/35e32d582eee4931a1db5519b345b2ee |
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