Patil Chandrashekhar S, Singh Vijay Pal, Kulkarni Shrinivas K
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160 014, India.
Inflammopharmacology. 2005;13(5-6):467-78. doi: 10.1163/156856005774649359.
Experimental studies have indicated the importance of cAMP and cGMP in modulation of peripheral sensory neurons leading to hyperalgesic response. The concentration of both depends upon the activity of phosphodiesterase, which is responsible for their degradation. The aim of the present study was to evaluate the effect of the PDE-5 inhibitor sildenafil on central or peripheral administration in formalin-induced hyperalgesia in rats. Sildenafil dose-dependently and significantly attenuated both the early and late phase of formalin-induced hyperalgesia on central administration. However, sildenafil on peripheral administration inhibited only the late phase of formalin-induced hyperalgesia in rats. The anti-nociceptive effect of sildenafil was blocked by L-NAME, a non-selective NOS inhibitor, and methylene blue (MB), a guanylate cyclase inhibitor, but sildenafil itself had little or no effect on the first phase of the formalin test in rats. The results from the present study indicates that sildenafil, besides peripheral actions, has a central anti-nociceptive effect, which may be due to activation of the NO-cGMP pathway, as this effect was blocked by L-NAME and MB. PDE-5 inhibitors could be considered as a new class of anti-nociceptive agents for future drug development.
实验研究表明,环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP)在调节外周感觉神经元导致痛觉过敏反应中具有重要作用。两者的浓度取决于磷酸二酯酶的活性,该酶负责它们的降解。本研究的目的是评估磷酸二酯酶5(PDE-5)抑制剂西地那非对大鼠福尔马林诱导的痛觉过敏进行中枢或外周给药的效果。西地那非中枢给药时剂量依赖性且显著减轻福尔马林诱导的痛觉过敏的早期和晚期阶段。然而,西地那非外周给药仅抑制大鼠福尔马林诱导的痛觉过敏的晚期阶段。西地那非的抗伤害感受作用被非选择性一氧化氮合酶(NOS)抑制剂L-精氨酸甲酯(L-NAME)和鸟苷酸环化酶抑制剂亚甲蓝(MB)阻断,但西地那非本身对大鼠福尔马林试验的第一阶段几乎没有影响。本研究结果表明,西地那非除了具有外周作用外,还具有中枢抗伤害感受作用,这可能是由于一氧化氮-环磷酸鸟苷(NO-cGMP)途径的激活,因为这种作用被L-NAME和MB阻断。PDE-5抑制剂可被视为未来药物开发中的一类新型抗伤害感受药物。