Cannabinoid receptor GPR18 activation relieved bladder pain and overactivity in rats
Activating the cannabinoid receptor GPR18 with Resolvin D2 reduced pain and improved bladder function in a rat model of interstitial cystitis, likely by inhibiting TRPV1 pain receptors.
Quick Facts
What This Study Found
Intrathecal injection of Resolvin D2 (a GPR18 agonist) increased paw withdrawal threshold and micturition interval in rats with cyclophosphamide-induced cystitis. The GPR18 antagonist O-1918 blocked these effects. GPR18 colocalized with TRPV1 in dorsal root ganglia, and RvD2 decreased capsaicin-induced calcium influx.
Key Numbers
GPR18 mRNA and protein expression reduced in bladder and DRG of cystitis rats; RvD2 increased paw withdrawal threshold and micturition interval; O-1918 blocked therapeutic effects
How They Did This
Researchers induced cystitis in rats using cyclophosphamide, then administered intrathecal Resolvin D2 (GPR18 agonist) and O-1918 (GPR18 antagonist). Pain was assessed via paw withdrawal threshold, bladder function via cystometry, and molecular mechanisms via RT-PCR, Western blotting, immunofluorescence, and calcium imaging.
Why This Research Matters
Interstitial cystitis/bladder pain syndrome affects millions and has limited treatment options. Identifying GPR18 as a therapeutic target through the endocannabinoid system opens a new pathway for pain and bladder dysfunction management.
The Bigger Picture
GPR18 is a lesser-known member of the cannabinoid receptor family. This study expands understanding of how the endocannabinoid system modulates pain beyond the well-studied CB1 and CB2 receptors.
What This Study Doesn't Tell Us
Animal model only. Intrathecal drug delivery is not a practical clinical approach. Single disease model. Short-term outcomes measured.
Questions This Raises
- ?Could GPR18 agonists be developed for oral or topical administration?
- ?Does GPR18 play a role in other chronic pain conditions?
- ?Would combining GPR18 and CB2 activation produce additive pain relief?
Trust & Context
- Key Stat:
- GPR18 activation via Resolvin D2 relieved both pain and bladder overactivity
- Evidence Grade:
- Well-designed animal study with mechanistic pathway elucidation, but no human data.
- Study Age:
- Published in 2021.
- Original Title:
- Activation of GPR18 by Resolvin D2 Relieves Pain and Improves Bladder Function in Cyclophosphamide-Induced Cystitis Through Inhibiting TRPV1.
- Published In:
- Drug design, development and therapy, 15, 4687-4699 (2021)
- Authors:
- Lu, Qudong, Yang, Yang(3), Zhang, Hengshuai, Chen, Cheng, Zhao, Jiang, Yang, Zhenxing, Fan, Yi, Li, Longkun, Feng, Huan, Zhu, Jingzhen, Yi, Shanhong
- Database ID:
- RTHC-03299
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
What is GPR18?
GPR18 is a receptor in the cannabinoid receptor family that participates in pain modulation and bladder function. It is less well-studied than the main CB1 and CB2 receptors.
How does this relate to cannabis?
GPR18 belongs to the same receptor family that cannabis compounds interact with. This study used a non-cannabis compound (Resolvin D2) to activate this receptor, suggesting the broader endocannabinoid system plays a role in bladder pain.
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Cite This Study
https://rethinkthc.com/research/RTHC-03299APA
Lu, Qudong; Yang, Yang; Zhang, Hengshuai; Chen, Cheng; Zhao, Jiang; Yang, Zhenxing; Fan, Yi; Li, Longkun; Feng, Huan; Zhu, Jingzhen; Yi, Shanhong. (2021). Activation of GPR18 by Resolvin D2 Relieves Pain and Improves Bladder Function in Cyclophosphamide-Induced Cystitis Through Inhibiting TRPV1.. Drug design, development and therapy, 15, 4687-4699. https://doi.org/10.2147/DDDT.S329507
MLA
Lu, Qudong, et al. "Activation of GPR18 by Resolvin D2 Relieves Pain and Improves Bladder Function in Cyclophosphamide-Induced Cystitis Through Inhibiting TRPV1.." Drug design, 2021. https://doi.org/10.2147/DDDT.S329507
RethinkTHC
RethinkTHC Research Database. "Activation of GPR18 by Resolvin D2 Relieves Pain and Improve..." RTHC-03299. Retrieved from https://rethinkthc.com/research/lu-2021-activation-of-gpr18-by
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.