Effect of diabetes on the mechanisms of intrathecal antinociception of sildenafil in rats

Inhibition of Inflammatory Pain by Activating B-Type Natriuretic Peptide Signal Pathway in Nociceptive Sensory Neurons

“…The NPR-A-mediated cGMP generation can be enhanced in the presence of different phosphodiesterase inhibitors (de Vente et al, 2006). Accordingly, inhibition of cGMP degradation by intrathecal administration of the phosphodiesterase 5 inhibitor sildenafil reduces inflammatory pain induced by formalin (Torres-Lopez et al, 2002;Araiza-Saldana et al, 2005). Therefore, the nociceptive afferent transmission may be regulated by factors that alter intracellular level of cGMP.…”

“…Subcutaneous injection of formalin into the left hindpaw of adult rats produced a typical pattern of flinching behavior (Fig. 8 A) characterized by a biphasic time course (1ϳ10 min for phase 1, 10ϳ60 min for phase 2) (Araiza-Saldana et al, 2005). Intrathecal injection of BNP (applied 10 min before intraplantar formalin injection) induced a dose-dependent inhibitory effect on both phases of the formalin test ( p Ͻ 0.001 for 100 ng, 500 ng, and 2 g of BNP vs vehicle, respectively, ANOVA; phase 1: p ϭ 0.099, 0.026, and 0.034, and phase 2: p ϭ 0.007, Ͻ0.001, and ϭ 0.004, for 100 ng, 500 ng, and 2 g of BNP vs vehicle, respectively; n ϭ 7 rats/group) (Fig.…”

Role of PKG-L-type calcium channels in the antinociceptive effect of intrathecal sildenafil

“…The following drugs were used in this study: sildenafil (Pfizer Korea, Korea), (9S,10R,12R)-2,3,9,10,11,12-Hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3,2,1-kl]pyrrolo[3,4-i][1,6]benzodi azocine-10-carboxylic acid, methyl ester (KT 5823; Tocris, UK), and 2,5-Dimethyl-4-[2-(phentylmethyl)benzoyl]-1H-pyrrole-3-carboxylic acid methyl ester (FPL 64176; Tocris, UK). Sildenafil and FPL 64176 were dissolved in 20% dimethylsulfoxide (DMSO; Sigma-Aldrich, USA), and KT 5823 was dissolved in normal saline.…”

“…Cyclic guanosine monophosphate (cGMP) has become increasingly important in the understanding of antinociceptive mechanisms in the central nervous system [1,13,16,21]. The concentration of intracellular cGMP is regulated by the action of guanylyl cyclase, as well as by its rate of degradation by cGMP-specific phosphodiesterase [2,14].…”

“…Sildenafil (Viagra) is clinically used to treat impotence as a cGMP-specific phosphodiesterase 5 inhibitor [4,10] and produces antinociception in animal pain model, which is mediated through the nitric oxide-cGMP-PKG-potassium channel pathway or opioid receptors [1,13,21]. It has been recently reported that sildenafil inhibits cerebroarterial vasoconstriction by blocking L-type calcium channels [15].…”