In this study the antinociceptive and anti-inflammatory effects of the CB1 receptor antagonist was investigated in diet induced obese female rats and lean rats with arthritis which was induced by complete Freund’s adjuvant (CFA) which was injected in to the right hind paw. This was done to test the fact that obesity is a risk factor in inflammation-based diseases such as arthritis. Oral rimonabant was given to the rats and various issues were subsequently assessed such as oedema, global arthritis score, ankle widths, nitrite/nitrate levels, hyper sensitivity to heat or cold and hypersensitivity to stimuli such as a light touch.
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Rimonabant is a selective and potent cannabinoid CB1 receptor antagonist which appears to inhibit food intake and obesity activities in the body. This cannabinoid is used as a tool to investigate how cannabinoids work. One of these effects seem to be a blocking of activation of cannabinoid CB1 receptors under certain conditions. Obesity is associated with chronic low grade inflammation and could be a risk factor for diseases such as arthritis. Rimonabant may be able to reduce body weight as well as cardiovascular metabolic risk factors in obese people. Rimonabant also showed improvement in inflammation levels in studies done on rats and mice under laboratory conditions. Rimonabant also showed antinociceptive effects after repeated treatments which means that it may be an effective analgesic for nerve pain which is often unresponsive to opioids. Rimonabant showed anti-inflammatory, anti-obesity and antinociceptive actions, so this cannabinoid CB1 antagonist was chosen as the treatment for pain and inflammation on lean and diet induced obese female rats of the same age.
Arthritis was induced through injecting complete Freund’s adjuvant (CFA) in to a rear paw in the rats. Half of the rats were fed an obesity inducing diet while the lean rats were fed a conventional pellet diet. This was done for 36 weeks while housing the rats under a controlled environment. Test animals were injected with CFA while controls were injected with saline. This induced arthritis in the test animals in the specific paw with no other join involvement. Rimonabant was given for 7 days, starting from a week after the CFA injections. The induced inflammation was checked by measuring the paw oedema 1 week after CFA injection and after 7 days of rimonabant treatment as well as the ankle width and arthritis score on day 7, 10 and 14.
The CFA produced a more marked inflammatory response in the obese rats. After the first week, the arthritis scores and oedema volumes were much higher in the obese rats than the lean ones. After 7 days of treatment with rimonabant the inflammation in the obese rats subsided in the obese rats but not in the lean rats. By the end of the first week of rimonabant treatment, the oedema and arthritis score were similar in both lean and obese rats. The ankle width in the obese rats were also significantly reduced within the first 7 days of treatment. The control rats showed no change in paw or ankle width in both the lean and obese rats.
After 7 days of treatment, thermal hyperalgesia was reduced in lean and obese rats by between 44% and 69% with the result being higher in obese rats. For allodynia, rimonabant was significantly more effective in the obese rats than in the lean ones, with lean rats being at 39% to 59% and obese rats being at between 68% and 78%. There was however no change in pain responses in the obese or lean rats. Rimonabant also reduced nitrate/nitrite levels in both lean and obese rats.
These findings are in line with the view that obesity is a mild inflammatory condition which also increases the susceptibility to inflammatory conditions such as arthritis. Vascular inflammatory reactions were also noted in the obese rats. Rimonabant has an antinociceptive action which can be effective in reducing obesity, treating neuropathic pain and inflammation, as well as reducing thermal hyperalgesia and mechanical allodynia in arthritic animals. The effects seem to be more prominent in obese rats than in lean ones. This may indicate that rimonabant may have therapeutic applications in treating established chronic inflammatory diseases.