Synergistic antinociception of intrathecal sildenafil with clonidine in the rat formalin test |
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Authors: | Myung Ha Yoon Chang Mo Kim Woong Mo Kim Yeo Ok Kim |
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Institution: | a Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, South Korea b Department of Anesthesiology and Pain Medicine, Chosun University, Medical School, Gwangju, South Korea c The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, South Korea |
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Abstract: | Spinal sildenafil (phosphodiesterase 5 inhibitor) and clonidine (alpha-2 adrenoceptor agonist) have shown antinociception. The author examined the properties of drug interaction after concurrent administration of intrathecal sildenafil-clonidine, and further clarified the reciprocity of sildenafil and clonidine. Catheters were inserted into the intrathecal space of male Sprague-Dawley rats. The formalin test was used as a nociceptive test, which was induced by subcutaneous injection of 50 µl of 5% formalin solution into the hindpaw. The pharmacological interaction was characterized using an isobolographic analysis. Intrathecal sildenafil and clonidine dose-dependently suppressed the flinching response observed during phase 1 and phase 2 in the formalin test. Isobolographic analysis revealed a synergistic interaction after intrathecal delivery of sildenafil-clonidine in both phases. Intrathecal yohimbine antagonized the antinociceptive action of intrathecal sildenafil during both phases in the formalin test. However, intrathecal ODQ failed to antagonize the antinociceptive action of intrathecal clonidine. These results suggest that sildenafil and clonidine, and the mixture of the two are effective against acute pain and facilitated pain state at the spinal level. Furthermore, synergism was noted after delivery of sildenafil-clonidine mixture. The antinociception of sildenafil can be modulated by spinal alpha-2 adrenoceptor, while the effect of clonidine is independent on the guanyly cyclase. |
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Keywords: | Antinociception Clonidine Sildenafil Synergistic interaction Alpha-2 adrenoceptor |
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