Sildenafil increases diclofenac antinociception in the formalin test

Asomoza-Espinosa, Raquel; Alonso-López, Rosario; Mixcoatl-Zecuatl, Teresa; Aguirre-Bañuelos, Patricia; Torres-López, Jorge Elías; Granados‐Soto, Vinicio

doi:10.1016/s0014-2999(01)00956-6

Cited by 44 publications

(23 citation statements)

References 24 publications

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“…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]. In addition to our study, another study showed that the PDE 5 inhibitor sildenafil enhanced diclofenac anti-nociceptive effects in formalin tests [18]. Furthermore, one study demonstrated that the PDE 5 inhibitor tadalafil has analgesic effects on experimental arthritis by suppressing TNF alpha release in joints [19].…”

Section: Discussioncontrasting

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

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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: 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

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“…The effect of sildenafi l on PDE5 has been pointed as being responsible for its antinociceptive effect [5]. The NO/cGMP/PKG/KATP pathway has been reported as an additional mechanism of action of some peripheral analgesics such as diclophenac, dypirone, rofecoxib, ketorolac and central-acting drugs such as morphine [4,6,16]. Sachs et al [12] have described this sequence of events that ends with the opening of potassium channels as a mechanism antagonistic to the hyperalgesic state that occurs in infl amed tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have consistently found that sildenafi l produces antinociception in the formalin test in rats [3,4] and in the writhing response induced by acetic acid in mice [5,6]. Mixcoatl-Zecuatl et al [3] and Asomoza-Espinosa et al [4] have suggested that sildenafi l produces its antinociceptive effect through the accumulation of cyclic GMP as a suggested that sildenafi l causes antinociception through the activation of the NO-cyclic GMP pathway [5,6].…”

Section: Introductionmentioning

confidence: 95%

Role of NO/cGMP/KATP pathway in antinociceptive effect of sildenafil in zymosan writhing response in mice

et al. 2007

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“…Diclofenac can inhibit voltage-dependent Na ＋ channels in cardiac myoblasts and neurons (Lee et al, 2003;Yang and Kuo, 2005;Fei et al, 2006). It also activates neuronal K ＋ channels, such as the transient outward K ＋ currents and the ATP-sensitive potassium (KATP) channel (Tonussi and Ferreira, 1994;Asomoza-Espinosa et al, 2001;Alves and Duarte, 2002;Ortiz et al, 2002;Liu et al, 2005). However, to date, there has been no evidence of a suppressive effect of diclofenac on LCC, which is critical in working myocytes.…”

Section: Introductionmentioning

confidence: 99%

Diclofenac, a Non-steroidal Anti-inflammatory Drug, Inhibits L-type Ca2+ Channels in Neonatal Rat Ventricular Cardiomyocytes

Yarishkin

Hwang

Kim

et al. 2009

Korean J Physiol Pharmacol

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A non-steroidal anti-inflammatory drug (NSAID) has many adverse effects including cardiovascular (CV) risk. Diclofenac among the nonselective NSAIDs has the highest CV risk such as congestive heart failure, which resulted commonly from the impaired cardiac pumping due to a disrupted excitationcontraction (E-C) coupling. W e investigated the effects of diclofenac on the L-type calcium channels which are essential to the E-C coupling at the level of single ventricular myocytes isolated from neonatal rat heart, using the whole-cell voltage-clamp technique. Only diclofenac of three NSAIDs, including naproxen and ibuprofen, significantly reduced inward whole cell currents. At concentrations higher than 3 μM, diclofenac inhibited reversibly the Na ＋ current and did irreversibly the L-type Ca 2＋ channels-mediated inward current (IC50=12.89± 0.43 μM) in a dose-dependent manner. However, nifedipine, a well-known L-type channel blocker, effectively inhibited the L-type Ca 2＋ currents but not the Na ＋ current. Our finding may explain that diclofenac causes the CV risk by the inhibition of L-type Ca 2＋ channel, leading to the impairment of E-C coupling in cardiac myocytes.

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Sildenafil increases diclofenac antinociception in the formalin test

Cited by 44 publications

References 24 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

Role of NO/cGMP/KATP pathway in antinociceptive effect of sildenafil in zymosan writhing response in mice

Diclofenac, a Non-steroidal Anti-inflammatory Drug, Inhibits L-type Ca2+ Channels in Neonatal Rat Ventricular Cardiomyocytes

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