## 4 Discussion
This observation implies that the damage process has stopped. Considering the histological results together, palm TRF, glucosamine sulphate, and the combination of both can halt cartilage deterioration, but it takes more time for the cartilage lesions to heal completely. MIA-induced osteoarthritis model was reported to reflect pain, mechanical and temperature hypersensitivity [35]. Owing to these changes, rats of this disease model alsodemonstrated reduced hindpaw grip strength, as measured via the digital grip strength meter [36]. Due to the absence of a similar device in the authors' setting, an inverted screen grip strength test was used [24]. This test has been adopted by multiples studies as a functional assessment of rodents in various disease models [37; 38]. Upon osteoarthritis induction, a significant decrease in grip strength was noted for all rats, except the T + G group. Two weeks after induction, the difference in grip strength between the N and O groups was not significant, but the T + G group continued to show significantly better performance than the O and T group. This observation reflects a rapid and continuous protection of joint function by the palm TRF and glucosamine sulphate in combination. Given that cartilage lesions were still found in the combination group, other factors might contribute to the improvement in grip strength. Inflammatory pain is associated with prostaglandandins release mediated by cyclooxygenase [39]. \(\gamma\)-tocotrienol could decrease cyclooxygenase-2 expression in human gastric cancer cells [40]. Palm TRF (25-100 mg/kg for 4 weeks) has been reported to suppress hyperalgesia and allodynia in a rat model of diabetic neuropathy due to reduced inflammation and nitrosative stress [41]. A meta-analysis showed that glucosamine sulphate effectively reduces pain in patients with osteoarthritis, probably owing to its anti-inflammatory effects [42]. Although antinociceptive effects of the regimens were not assessed in this study, the anti-inflammatory functions of both TRF and glucosamine sulphate could have contributed to the increased grip strength of the animals. Besides, MIA induction also caused an initial reduction in body weight of rats in this study, which rebounded after 2-3 weeks. Previous studies have reported that osteoarthritis induced by MIA is associated with the altered locomotion of rats, particularly the rearing and standing activities necessary when the rats reach for food [43; 44]; this is probably due to joint pain. Thus, the reduction in body weight observed in this study might be associated with reduced food intake, although it was not recorded by the researchers. Furthermore, the rats receiving treatments regained body weight faster than the untreated rats with osteoarthritis, implying faster function recovery, which coincides with grip strength data. The current study is not without its limitations. Grip strength is the only functional outcome measured due to the technical limitations of the authors' laboratory. Weight-bearing and rearing activities should be monitored in future studies. The mechanism of palm TRF and glucosamine sulphate in preventing osteoarthritis is not reported in the current study. The inflammatory, oxidative stress and cartilage markers in joint tissues such as cartilage, synovium and infrapatellar fat pad should be investigated in future studies. Nevertheless, this study has highlighted the potential additive effects of palm TRF and glucosamine sulphate in preventing osteoarthritis and, especially, improving the functional outcomes for the rats. This effect should be investigated further for potential application in patients with osteoarthritis.