Nöropatik farelerde oluşan mekanik allodini ve hiperaljezi üzerine minosiklin'in tek başına ve morfin ile birlikte kullanıldığındaki etkisi
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Tarih
2007
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info:eu-repo/semantics/openAccess
Özet
Bu çalışma siyatik siniri parsiyel olarak sıkıca bağlanmış nöropatik farelerde gelişen mekanik allodini ve termal hiperaljezi üzerine minosiklinin etkinliğini saptamak ve bu etki üzerine minosiklin ile morfinin etkileşimini belirlemek için yapılmıştır. Siyatik sinirin arka kısmının 1/3 ila 1/2' si sıkıca bağlanarak gerçekleştirilen parsiyel sinir ligasyonundan sonra, davranışsal belirtiler farelerin arka pençelerinin plantar yüzeylerinden test edildi. Sinir zedelenmesine bağlı olarak ortaya çıkan mekanik allodini ölçümleri Dynamic Plantar Aesthesiometer kullanılarak, termal hiperaljezi ise bir plantar analjezi metre aracılığı ile fare pençesinde ölçüldü. Nöropatik farelerde cerrahi girişimi takiben 1. günden başlayarak belirgin allodini ve hiperaljezi gelişimi gözlendi. Minosiklinin (5, 15, 45 mg/kg, i.p.) hem preemptif hem de terapötik uygulaması mekanik allodini ve termal hiperaljezi oluşumunu engelledi. 5 gün süreyle günde iki kez morfin (10 mg/kg, s.c.) uygulandığında, morfinin analjezik etkisine karşı geliştiği bilinen toleransın antiallodinik etkisinde görülmediği, sadece antihiperaljezik etkisine karşı ortaya çıktığı belirlendi. Minosiklinin hem preemptif hem de terapötik uygulamalarının ise morfinin antiallodinik ve antihiperaljezik etkinliğini değiştirmediği gözlendi. Bu sonuçlar minosiklinin gelecekteki nöropatik ağrı tedavisi için ümit veren bir ilaç olduğunu göstermektedir, ancak morfin ve minosiklin arasındaki etkileşimin tam olarak açıklanabilmesi ve bunun sonucunda morfine karşı gelişen analjezik toleransın engellenebilmesi için daha kapsamlı araştırmalara gereksinim vardır. Anahtar sözcükler: mikroglia; hiperaljezi; minosiklin; morfin; nöropatik ağrı
The present study was undertaken to determine the effects of minocycline on mechanical allodynia and thermal hyperalgesia in mice with partial tight ligation of the sciatic nerve, and how minocycline interacts with morphine in this condition. Mice was tested for behavioral effects on the plantar surface of the hind paw after the surgery, in which a partial nerve ligation of the sciatic nerve was made by tightly tying 1/3 to 1/2 of the dorsal portion of the sciatic nerve. A plantar analgesic meter was used to assess thermal hyperalgesia, and nerve injury-induced mechanical hyperalgesia was assessed with Dynamic Plantar Aesthesiometer. Beginning from the 1st day following the surgery, marked allodynia and hyperalgesia developed in neuropathic mice. Both preemptive and therapeutic treatments with minocycline (5, 15, 45 mg/kg, i.p.) blocked mechanical allodynia and thermal hyperalgesia. An analgesic tolerance against antihyperalgesic, but not antiallodynic, effect was observed with twice daily injections of morphine (10 mg/kg, s.c.) for 5 days. Neither preemptive nor therapeutic treatments of minocycline changed the efficacy of morphine on allodynia and hyperalgesia. These results suggest that minocycline may have clinical utility in neuropathic pain therapy in the future; however, further experiments are required to delineate the interaction between morphine and minocycline and to prevent the development of tolerance to the antinociceptive effects of morphine. Key words: microglia; hyperalgesia; minocycline; morphine; neuropathic pain
The present study was undertaken to determine the effects of minocycline on mechanical allodynia and thermal hyperalgesia in mice with partial tight ligation of the sciatic nerve, and how minocycline interacts with morphine in this condition. Mice was tested for behavioral effects on the plantar surface of the hind paw after the surgery, in which a partial nerve ligation of the sciatic nerve was made by tightly tying 1/3 to 1/2 of the dorsal portion of the sciatic nerve. A plantar analgesic meter was used to assess thermal hyperalgesia, and nerve injury-induced mechanical hyperalgesia was assessed with Dynamic Plantar Aesthesiometer. Beginning from the 1st day following the surgery, marked allodynia and hyperalgesia developed in neuropathic mice. Both preemptive and therapeutic treatments with minocycline (5, 15, 45 mg/kg, i.p.) blocked mechanical allodynia and thermal hyperalgesia. An analgesic tolerance against antihyperalgesic, but not antiallodynic, effect was observed with twice daily injections of morphine (10 mg/kg, s.c.) for 5 days. Neither preemptive nor therapeutic treatments of minocycline changed the efficacy of morphine on allodynia and hyperalgesia. These results suggest that minocycline may have clinical utility in neuropathic pain therapy in the future; however, further experiments are required to delineate the interaction between morphine and minocycline and to prevent the development of tolerance to the antinociceptive effects of morphine. Key words: microglia; hyperalgesia; minocycline; morphine; neuropathic pain
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Anahtar Kelimeler
Eczacılık, Farmakoloji, Pharmacy, Pharmacology