Milnacipran attenuated carrageenan-induced hyperalgesia and inflammation in male rats; the involvement of MPO activity and oxidative stress

Background and Aim : Many injuries caused pain and inflammation, which are one of the major challenges for physicians. Existing anti-inflammatory and analgesic drugs such as NSAIDs and opioids have many side effects. In this study, the analgesic and the anti-inflammatory effects of milnacipran were investigated on carrageenan-induced nociception and inflammation in male rats.Methods : Pain and inflammation were induced by intraplantar injection of λ-carrageenan (1% v/v) in the right hind paw. Indomethacin (10 mg/kg: i.p) or milnacipran (10, 20 and 40 mg/kg: i.p) were administered half an hour before carrageenan injection. Analgesia was measured by Hot plate test, and inflammation was assessed by plethysmometer. Finally, the effect of carrageenan and milnacipran on lipid peroxidation, TNF-α, IL-1ß, IL-6, myeloperoxidase (MPO) activity, nitric oxide (NO) and total antioxidant capacity (TAC) status evaluated in the hind paw tissue.Results : The results showed that carrageenan caused hyperalgesia and inflammation in the hind paw tissue. Milnacipran (20 and 40 mg/kg: i.p) significantly attenuated (p<0/01) inflammation percentage and significantly increased (p<0.001) nociception threshold. Also, milnacipran (20 and 40 mg/kg) significantly suppressed malondialdehyde (MDA), NO levels (p<0.05), MPO activity, TNF-α, IL-1ß and IL-6 (p<0.001) following carrageenan ijection. Additionally, milnacipran (10, 20 and 40 mg/kg) augmented TAC status subsequent to intraplantar injection of carrageenan in the hind paw tissue in a significant level (p<0.05).Conclusion : In the present study, milnacipran showed anti-nociceptive and anti-inflammatory effects on carrageenan-induced hyperalgesia and inflammation. Milnacipran reduced inflammatory edema and increased the paw withdrawal threshold probably through suppression of MDA, NO, TNF-α, IL-1ß and IL-6 levels and MPO activity and increasing of TAC status in the hind paw tissue. Therefore, milnacipran holds important potential as an anti-inflammatory and anti-nociceptive drug. Although, there is need more clinical trial studies to prove this issue.

Keywords:

Carrageenan , Milnacipran , Plethysmometer , Pain and Inflammation , Analgesia , Myeloperoxidase , Malondialdehyde , Rat