Suppression of joint pain in transient receptor potential vanilloid 4 knockout rats with monoiodoacetate-induced osteoarthritis. (9th September 2021)

• Record Type: Journal Article
• Authors: Soga, Masahiko; Izumi, Takaya; Nanchi, Isamu; Horita, Narumi; Yamamoto, Miyuki; Kawasaki, Shiori; Ogawa, Koichi; Fujita, Masahide; Morioka, Yasuhide
• Is Part Of: Pain reports. Volume 6:Number 3(2021)
• Page Start: e951
• Publication Date: 2021-09-09
• Subjects: TRPV4 -- osteoarthritis -- monoiodoacetate -- dorsal root ganglion
• DOI: 10.1097/PR9.0000000000000951
• Languages: English
• ISSNs: 2471-2531

Abstract

Abstract : Supplemental Digital Content is Available in the Text. Knee joint pain in osteoarthritis model rats is caused by the sensitization of transient receptor potential vanilloid 4 in the dorsal root ganglion neurons Abstract: Introduction: Transient receptor potential vanilloid 4 (TRPV4) modulates osteoarthritic (OA) pain in animal models. However, the pathophysiological function of TRPV4 in regulating OA pain remains poorly understood. Methods: We developed TRPV4-knockout (TRPV4-KO) rats and assessed the effects of Trpv4 gene deficiency in a monoiodoacetate (MIA)-induced OA pain model (MIA rats) by examining pain-related behavior, pathological changes, and electrophysiological changes in dorsal root ganglion (DRG) neurons. The changes detected in TRPV4-KO rats were confirmed in wild-type rats using a TRPV4 antagonist. Results: Transient receptor potential vanilloid 4–KO rats showed the same pain threshold as wild-type rats for thermal or pressure stimuli under normal conditions. Trpv4 gene deletion did not suppress the development of osteoarthritis pathologically in MIA rats. However, the OA-related mechanical pain behaviors observed in MIA rats, including decreased grip strength, increased mechanical allodynia, and reduced weight-bearing on the ipsilateral side, were completely suppressed in TRPV4-KO rats. The DRG neurons in wild-type but not TRPV4-KO MIA rats were depolarized with increased action potentials. Transient receptor potential vanilloid 4 antagonist treatments recapitulated the effects of genetic Trpv4 deletion. Conclusion: Transient receptor potential vanilloid 4 was sensitized in the DRG neurons of MIA rats and played a critical role in the development of OA pain. These results suggest that the inhibition of TRPV4 might be a novel potent analgesic strategy for treating OA pain.