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Cukurova Med J. 2015; 40(1): 42-54

The Role of Nitrergic System on The Effects of Tramadol and Agmatine in An Experimental Neuropathic Pain Model

Soner Mete, Fazilet Aksu.

Purpose: Anticonvulsants, antidepressants, local anesthetics, sodium channel blockers, drugs such as narcotic analgesics but also on alternative therapies has been extensively studied in the treatment of neuropathic pain (NP) which reduces quality of life. Tramadol (TR) which is one of these drugs has been reported to reduce the symptoms of neuropathic pain. Agmatine (AG) is a new neuromediators in the central nervous system and acute and chronic experimental pain studies have reported that the antinociceptive effects. In our study, TR and AG when used alone and in combination antiallodynic effects and this effect was aimed to investigate the role of nitrergic system created by the sciatic nerve ligation model of neuropathic pain in.
Materials and Methods: Experimental mononeuropathy was developed by ligation of right sciatic nerve of mice under general anesthesia. Mice were divided into naive, sham, neuropathy control (NP) and NP + drugs groups. Neuropathic pain was evaluated by cold plate test after two weeks operation. The antiallodynic effects of TR and AG were assessed. Nitric oxide precursor L-arjinin (LA), nitric oxide synthase (NOS) inhibitors L-NAME, L-NMMA and 7-NI were used to investigate the role of nitric oxide in these effects. Lastly, the combined effects of TR and AG was determined.
Results: According to the results of experiments, TR and AG, developed neuropathy in mice showed the antiallodynic effects by extending cold plate latency (CPL). LA did not changed the effects of TR and AG. All NOS inhibitors enhanced the antiallodynic effect of TR while only L-NAME enhanced the effect of AG. The combined use of TR and AG showed greater antiallodynic effect than the effects of individual drugs.
Conclusion: According to findings, TR and AG are promising drugs for treatment of NP and combined use of these drugs may be more effective. The role of inhibition of NOS in the antiallodynic effects of these two drugs were different in extent and the other possible mechanisms beside NOS inhibition may involve in the effects of these two drugs.

Key words: Agmatine, Nitrergic system, Neuropathic pain, Tramadol

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