The effects of intra-articular resiniferatoxin on monosodium iodoacetate-induced osteoarthritic pain in rats

This study was performed to investigate whether an intra-articular injection of transient receptor potential vanilloid 1 (TRPV1) receptor agonist, resiniferatoxin (RTX) would alleviate behavioral signs of arthritic pain in a rat model of osteoarthritis (OA). We also sought to determine the effect of RTX treatment on calcitonin gene-related peptide (CGRP) expression in the spinal cord. Knee joint inflammation was induced by intra-articular injection of monosodium iodoacetate (MIA, 8 mg/50 microl) and weight bearing percentage on right and left hindpaws during walking, paw withdrawal threshold to mechanical stimulation, and paw withdrawal latency to heat were measured to evaluate pain behavior. Intra-articular administration of RTX (0.03, 0.003 and 0.0003%) at 2 weeks after the induction of knee joint inflammation significantly improved reduction of weight bearing on the ipsilateral hindlimb and increased paw withdrawal sensitivity to mechanical and heat stimuli. The reduction of pain behavior persisted for 3~10 days according to each behavioral test. The MIA-induced increase in CGRP immunoreactivity in the spinal cord was decreased by RTX treatment in a dose-dependent manner. The present study demonstrated that a single intra-articular administration of RTX reduced pain behaviors for a relatively long time in an experimental model of OA and could normalize OA-associated changes in peptide expression in the spinal cord.

Anti-inflammatory effect of egg white-chalcanthite and purple bamboo salts mixture on arthritis induced by monosodium iodoacetate in Sprague-Dawley rats / 한국실험동물학회지

The aim of this study is to investigate the potential of anti-osteoarthritis effects on egg white-chalcanthite (EC), purple bamboo salts (PBS), and a mixture of EC and PBS (EC+PBS). EC is a mixture of egg white and pulverized chalcanthite. PBS has been widely used as one of functional foods in Korea and shows unique features compared with common salt. Osteoarthritis was induced by intra-articular injection of monosodium iodoacetate (MIA, 4mg/kg bw) in Sprague-Dawley (SD) rats. Test substances were administered once daily for 6 weeks at doses of 10 mg EC, EC+100 mg PBS, EC+200 mg PBS before and after MIA injection. Each substance was assessed by blood chemistry parameters, and by serum cytokines including IL-1β and IL-6, and nitric oxide (NO) and prostaglandin-E2 (PGE2). Structural changes of articular cartilage were also evaluated by histopathological examination. As a result, body weight and blood chemistry parameter were not different in all experimental groups. EC+PBS mixture reduced the production of PGE2, NO, IL-1β, and IL-6. In histological grade of osteoarthritis, EC+PBS mixture had a tendency to ameliorate damage of articular cartilage induced by MIA in a dose-dependent manner. In conclusion, EC+PBS mixture was demonstrated to have a potential for anti-inflammatory effect against osteoarthritis induced by MIA in a dose-dependent manner.

Ursodeoxycholic Acid Ameliorates Pain Severity and Cartilage Degeneration in Monosodium Iodoacetate-Induced Osteoarthritis in Rats

Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage. And, increased oxidative stress plays a relevant role in the pathogenesis of OA. Ursodeoxycholic acid (UDCA) is a used drug for liver diseases known for its free radical-scavenging property. The objectives of this study were to investigate the in vivo effects of UDCA on pain severity and cartilage degeneration using an experimental OA model and to explore its mode of actions. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration UDCA was initiated on the day of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-1beta (IL-1beta), IL-6, nitrotyrosine and inducible nitric oxide synthase (iNOS) in knee joints. UDCA showed an antinociceptive property and attenuated cartilage degeneration. OA rats given oral UDCA significantly exhibited a decreased number of osteoclasts in subchondral bone legion compared with the vehicle-treated OA group. UDCA reduced the expression of IL-1beta, IL-6, nitrotyrosine and iNOS in articular cartilage. UDCA treatment significantly attenuated the mRNA expression of matrix metalloproteinase-3 (MMP-3), -13, and ADAMTS5 in IL-1beta-stimulated human OA chondrocytes. These results show the inhibitory effects of UDCA on pain production and cartilage degeneration in experimentally induced OA. The chondroprotective properties of UDCA were achieved by suppressing oxidative damage and inhibiting catabolic factors that are implicated in the pathogenesis of cartilage damage in OA.