How to calculate percentage inhibition of paw volume in collagen induced arthritis
Answers
he aim of this study is to evaluate the analgesic and anti-inflammatory activities of atorvastatin and simvastatin in different experimental models in mice and rats.
Materials and Methods:
Analgesic activity of simvastatin and atorvastatin was assessed in tail flick model in rats (n = 6), where it was compared with aspirin and tramadol and in acetic acid induced writhing in mice (n = 6), where it was compared with aspirin. Anti-inflammatory activity of statins was evaluated using carrageenin induced paw edema and formalin induced arthritis in rats.
Results:
In the tail flick method, analgesic effect of tramadol was significantly more than the other drugs except at two observation times, when it was comparable to simvastatin and atorvastatin. Effect of simvastatin was found to be comparable to aspirin. In acetic acid induced writhing method, analgesic activity of simvastatin was comparable to that of aspirin while that of atorvastatin was significantly less. In carrageenin induced paw edema in rats, both simvastatin and atorvastatin showed anti-inflammatory activity which was comparable to aspirin. Both the statins exhibited significant anti-inflammatory activity (P < 0.01) in formalin induced arthritis model though less than aspirin (P < 0.05).
Conclusion:
The results of this study if substantiated by further experimental and clinical research suggest that simvastatin and atorvastatin may play an adjuvant role, which may be particularly beneficial in the treatment of inflammatory disorders, especially when there is coexisting dyslipidemia.
KEY WORDS: Formalin induced arthritis, paw edema, statins, tail-flick method, writhing
Go to:
Introduction
Drugs commonly used in modern medicine for suppression of pain and inflammation like non-steroidal anti-inflammatory drugs and corticosteroids provide only symptomatic relief. Long-term use of these drugs is associated with serious adverse effects. Hence, the search for a new, safe analgesic and anti-inflammatory drug is ongoing. Introduced in 1980, statin group of drugs are most efficacious and well-tolerated in the treatment of hyperlipidemia. Statins are widely used for the prevention of cardiovascular diseases. Although the beneficial effects of statins in preventing cardiovascular diseases may derive from their lipid-lowering activity, these drugs have also been shown to possess anti-inflammatory and immunomodulatory effects.[1] Indeed, several recent studies have demonstrated the ability of diverse statins to prevent chronic inflammation in vivo, and one clinical trial has shown the beneficial effects of atorvastatin in patients with rheumatoid arthritis.[2–5]
Statins have been shown to decrease the secretion of pro-inflammatory cytokines IL-6 (interleukin-6) and IL-8 (interleukin-8) from macrophages, and inhibit the release of the chemokine CCL2/MCP-1 (macrophage chemotactic protein-1) from these cells.[6,7] The molecular mechanisms sub serving such anti-inflammatory and/or immunomodulatory activities are unclear. Osteoarthritis is a common disorder that causes severe pain and immobility in the patient. Treatment of osteoarthritis in modern medicine is currently limited to drugs that provide only symptomatic relief, and these drugs are associated with serious adverse effects. Hence, research for finding a better and safe drug for osteoarthritis has been a continuous process. Patients of hyperlipidemia are often overweight and more likely to suffer from osteoarthritis.[8] Considering various reports about anti-inflammatory and analgesic activity of statins, it is worthwhile to further evaluate these activities.
Atorvastatin has also been evaluated for its anti-inflammatory and analgesic activities; however, the results are controversial.[9] During our literature search we did not come across any study that evaluated the analgesic activity of simvastatin. Hence, this study was planned to evaluate and compare the anti-inflammatory and analgesic activities of simvastatin and atorvastatin in different animal models of inflammation and pain.
Go to:
Materials and Methods
Animals
Adult Wistar albino rats (Rattus norvegicus, weighing between 180 -280 g) and Swiss mice (weighing between 25–30 g) of either gender were used. Animals were kept in cages in temperature-regulated rooms with air-cooling and 12 hours light and dark cycle, and had free access to water and standard laboratory diet. They were allowed to acclimatize to the laboratory conditions for a period of one week, and kept fasting overnight prior to the experiment. The study was approved by the Institutional Animal Ethics Committee and all the experiments were performed as per the Committee for the purpose of control and supervision on experiments on animals (CPCSEA) guidelines.
Drugs and Reagents