Sensitization of transient receptor potential vanilloid 4 and increasing its endogenous ligand 5,6-epoxyeicosatrienoic acid in rats with monoiodoacetate-induced osteoarthritis
| Autor: | Masabumi Minami, Masayuki Imai, Minoru Hasegawa, Gaku Sakaguchi, Takeshi Yoshioka, Narumi Horita, Atsushi Morita, Junji Tsuchida, Yasuhide Morioka, Mikie Hinata, Kenichi Higashino, Shoji Yamane, Isao Fukuda, Masahiko Soga, Takao Sanaki, Minoru Ikeda, Toshiyuki Kanemasa, Miyuki Yamamoto, Sunao Imai |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
TRPV4 Agonist Male medicine.medical_specialty medicine.drug_class Morpholines Analgesic Pain TRPV Cation Channels Osteoarthritis Epoxyeicosatrienoic acid Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Dorsal root ganglion Leucine Internal medicine Ganglia Spinal medicine Animals Pyrroles Phosphorylation Receptor Pain Measurement Neurons Sulfonamides Hand Strength Antagonist medicine.disease Arthritis Experimental Iodoacetic Acid Rats Disease Models Animal 030104 developmental biology Anesthesiology and Pain Medicine medicine.anatomical_structure Endocrinology Neurology chemistry Neurology (clinical) |
| Zdroj: | Pain. 159(5) |
| ISSN: | 1872-6623 |
| Popis: | Transient receptor potential vanilloid 4 (TRPV4) receptor modulates pain, and this has been noted in several animal models. However, the involvement of TRPV4 in osteoarthritic (OA) pain remains poorly understood. This study assessed the functional changes in TRPV4 and the expression of its endogenous ligand 5,6-epoxyeicosatrienoic acid (5,6-EET) in a rat monoiodoacetate (MIA)-induced OA pain model (MIA rats). Monoiodoacetate-treated rats showed reduced grip strength as compared to sham-treated rats, and this loss in function could be recovered by the intraarticular administration of a TRPV4 antagonist (HC067047 or GSK2193874). By contrast, the intraarticular administration of the TRPV4 agonist, GSK1016790A, increased the pain-related behaviors in MIA rats but not in sham rats. TRPV4 expression was not increased in knee joints of MIA rats; however, the levels of phosphorylated TRPV4 at Ser824 were increased in dorsal root ganglion neurons. In addition, 5,6-EET was increased in lavage fluids from the knee joints of MIA rats and in meniscectomy-induced OA pain model rats. 5,6-EET and its metabolite were also detected in synovial fluids from patients with OA. In conclusion, TRPV4 was sensitized in the knee joints of MIA rats through phosphorylation in dorsal root ganglion neurons, along with an increase in the levels of its endogenous ligand 5,6-EET. The analgesic effects of the TRPV4 antagonist in the OA pain model rats suggest that TRPV4 may be a potent target for OA pain relief. |
| Databáze: | OpenAIRE |
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