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

Year 2015, Volume: 40 Issue: 1, 42 - 54, 09.09.2015

Soner Mete Fazilet Aksu

https://doi.org/10.17826/cutf.37615

Abstract

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 Araştırma Makalesi / Research Article 42 Cilt/Volume 40 Yıl/Year 2015 Nöropatik Ağrı-Tramadol-Agmatin 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.

Keywords

Agmatine, Nitrergic system, Neuropathic pain, Tramadol

Farelerde Oluşturulan Deneysel Nöropatik Ağrıya Karşı Tramadol ve Agmatinin Etkilerinde Nitrerjik Sistemin Rolü

Abstract

Amaç: Yaşam kalitesini düşüren nöropatik ağrının tedavisinde antikonvülsanlar, antidepresanlar, lokal anestezikler, sodyum kanal blokörleri, narkotik analjezikler gibi ilaçlar kullanılmakla birlikte alternatif tedaviler üzerine de yoğun olarak çalışılmaktadır. Bu ilaçlardan birisi olan tramadol (TR)’un, nöropatik ağrı semptomlarını azalttığı bildirilmiştir. Santral sinir sisteminde yeni bir nöromediyatör olarak bilinen agmatin (AG)’in ise deneysel akut ve kronik ağrı çalışmalarında antinosiseptif etkileri olduğu bildirilmiştir. Çalışmamızda, siyatik sinir parsiyel sıkı ligasyonu ile oluşturulan nöropatik ağrı modelinde TR ve AG'in tek başına ve kombine kullanıldıklarında antiallodinik etkileri ile bu etkilerde nitrerjik sistemin rolünün incelenmesi amaçlanmıştır. Materyal ve Metod: Çalışmada Balb/c türü erkek farelere anestezi altında sağ siyatik sinir bağlanarak nöropati oluşturuldu. Naive, sham, nöropati kontrol ve nöropati + ilaç grupları oluşturuldu. Nöropatik ağrı ameliyattan iki hafta sonra soğuk plaka testi ile değerlendirildi. TR ve AG’in antiallodinik etkileri incelendi. Bu etkilerde nitrerjik sistemin rolünü araştırmak üzere nitrik oksid prekürsörü L-arjinin (LA), nitrik oksid sentaz (NOS) inhibitörleri N-Nitro-L-arjinin Metil Ester (L-NAME), N-Metil-L-arjinin Asetat (L-NMMA) ve 7-Nitroindazol (7-NI) kullanıldı. Son olarak TR ve AG kombinasyonunun antiallodinik etkisi incelendi. Bulgular: Deneylerin sonuçlarına göre TR ve AG, nöropati oluşturulan farelerde cold-plate latensini uzatarak antiallodinik etki oluşturdu. LA, TR ve AG'in antiallodinik etkisini değiştirmedi. Uygulanan üç NOS inhibitörü TR’un antiallodinik etkisini artırırken, AG'in etkisini sadece L-NAME artırdı. Kombine uygulanan TR ve AG, tek başlarına göstermiş olduklarından daha yüksek bir antiallodinik etki gösterdiler. Sonuç: Bulgularımıza göre TR ve AG’in nöropatik ağrıda ümit veren bileşikler olduğu ve iki bileşiğin kombine kullanımının daha etkili olacağı söylenebilir. Bu maddelerin antiallodinik etkilerinde NOS inhibisyonunun rolü farklı derecelerdedir ve etkilerinde sadece NOS inhibisyonu değil, farklı mekanizmalar da rol oynayabilir.

Keywords

Agmatin, Nitrerjik sistem, Nöropatik Ağrı, Tramadol

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