Sildenafil-induced peripheral analgesia and activation of the nitric oxide–cyclic GMP pathway

Jain, Neil; Patil, Chandrashekhar S.; Singh, Àmarjit; Kulkarni, Shrinivas K.

doi:10.1016/s0006-8993(01)02673-7

Cited by 108 publications

(87 citation statements)

References 22 publications

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“…In previous studies with PDE 5 inhibitors, it was shown that they have peripheral antinociceptive effects by increasing intracellular cGMP levels [12,13]. In contrast to our study, one study showed that the PDE 5 inhibitor sildenafil had anti-nociceptive effects on acetic acid and carrageenan-induced hyperalgesia but not in tail flick test and hot plate test [17].…”

Section: Discussioncontrasting

confidence: 94%

“…Sildenafil and vardenafil are other known PDE5 inhibitors. Several studies into sildenafil and vardenafil using various experimental nociceptive models have shown that they have anti-nociceptive properties [12,13]. The aim of current study was to examine the possible involvement of tadalafil in nociception, morphine analgesia and morphine tolerance development in rats.…”

Section: Introductionmentioning

confidence: 99%

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Effects of the phosphodiesterase type-5 inhibitor tadalafil on nociception, morphine analgesia and tolerance in rats

Taşkıran

Özdemir

Arslan

et al. 2018

j-ebr

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A B S T R A C TAim: Tadalafil is a potent, selective and reversible inhibitor of phosphodiesterase type 5 (PDE5) enzyme breakdowning cyclic guanosine monophosphate (cGMP). In this study, we aimed to investigate the effects of tadalafil on nociception, morphine analgesia and tolerance. Methods: In this study, 54 Wistar Albino (230-250 g) male rats were used. First of all, four different doses (2, 4, 8, 16 mg/kg) were used to determine the optimum effective dose of tadalafil on nociception. Optimum activity was found at 8 mg/kg and animals were divided into six groups: Saline (S), 8mg/kg tadalafil, 5mg/kg morphine (M), M+ tadalafil, morphine tolerance (MT) and MT+ tadalafil. Saline was given to the control group, tadalafil intraperitoneally and morphine subcutaneously administered at the indicated doses. To develop tolerance to morphine, 10mg/kg morphine was injected daily in the morning and evening for five days and tolerance was evaluated with single dose of morphine on sixth days. The resulting analgesic effect was measured with hot plate and tail flick analgesia tests and recorded at 30th, 60th, 90th and 120th minutes. Results: Tadalafil showed anti-nociceptive effect when given alone at different doses (p<0.05). However, tadalafil significantly decreased the analgesic effect of morphine (p<0.05). In addition, tadalafil significantly increased the tolerance to morphine (p<0.05). Conclusions: The phosphodiesterase type 5 inhibitor tadalafil have anti-nociceptive properties and it decreases analgesic effect of morphine, in addition improves tolerance development. These effects probably may occur via NO/cGMP pathway.

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Section: Discussioncontrasting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Effects of the phosphodiesterase type-5 inhibitor tadalafil on nociception, morphine analgesia and tolerance in rats

Taşkıran

Özdemir

Arslan

et al. 2018

j-ebr

View full text Add to dashboard Cite

show abstract

“…In the acetic acidinduced writhing assay in mice, locally applied sildenafil exhibited an inhibitory effect that was enhanced by L-arginine and reduced by NOS or GC inhibitor, but NOS or GC inhibition alone failed to alter the response (312,561).…”

Section: Experimental Paradigms Yielding Inconsistent Results Regardimentioning

confidence: 94%

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

Pethő

Reeh

2012

Physiological Reviews

244

200

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Peripheral mediators can contribute to the development and maintenance of inflammatory and neuropathic pain and its concomitants (hyperalgesia and allodynia) via two mechanisms. Activation or excitation by these substances of nociceptive nerve endings or fibers implicates generation of action potentials which then travel to the central nervous system and may induce pain sensation. Sensitization of nociceptors refers to their increased responsiveness to either thermal, mechanical, or chemical stimuli that may be translated to corresponding hyperalgesias. This review aims to give an account of the excitatory and sensitizing actions of inflammatory mediators including bradykinin, prostaglandins, thromboxanes, leukotrienes, platelet-activating factor, and nitric oxide on nociceptive primary afferent neurons. Manifestations, receptor molecules, and intracellular signaling mechanisms of the effects of these mediators are discussed in detail. With regard to signaling, most data reported have been obtained from transfected nonneuronal cells and somata of cultured sensory neurons as these structures are more accessible to direct study of sensory and signal transduction. The peripheral processes of sensory neurons, where painful stimuli actually affect the nociceptors in vivo, show marked differences with respect to biophysics, ultrastructure, and equipment with receptors and ion channels compared with cellular models. Therefore, an effort was made to highlight signaling mechanisms for which supporting data from molecular, cellular, and behavioral models are consistent with findings that reflect properties of peripheral nociceptive nerve endings. Identified molecular elements of these signaling pathways may serve as validated targets for development of novel types of analgesic drugs.

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“…It is known that nitric oxide activates the guanylate-cyclase enzyme, which leads to cyclic guanosine monophosphate synthesis (cGMP) 2 . The NO/cGMP has a well established role in nociceptive pathways, as flags 3 , being also part of the pathway were morphine and its derivatives act 5,6 . Sildenafil, a potent phosphodiesterase-5 specific and selective inhibitor, has antinociceptive effects in several animal models, such as carrageenan-induced pain, writhing test 4 and in the second phase of the formalin test 5,6 , in addition to humans.…”

Section: Discussionmentioning

confidence: 99%

Uso do sildenafil no controle de dor neuropática após nefrectomia: relato de caso

Oliveira¹,

Xavier²,

Mendes³

2011

Rev. dor

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Sildenafil-induced peripheral analgesia and activation of the nitric oxide–cyclic GMP pathway

Cited by 108 publications

References 22 publications

Effects of the phosphodiesterase type-5 inhibitor tadalafil on nociception, morphine analgesia and tolerance in rats

Effects of the phosphodiesterase type-5 inhibitor tadalafil on nociception, morphine analgesia and tolerance in rats

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

Uso do sildenafil no controle de dor neuropática após nefrectomia: relato de caso

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