Anti-nociceptive and anti-allodynic activity of aliskiren in various pain models

Patel, Rakesh B.; Pawar, Vishwanath D.; Prajapati, Kanaiyalal D.; Sonara, Bhavin M.; Deshpande, Shrikalp; Shah, Gaurang; Jain, Mukul

doi:10.1016/j.ejphar.2013.03.036

Cited by 13 publications

(16 citation statements)

References 42 publications

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“…26,27,34 A study from another laboratory has also demonstrated the dose-dependent anti-nociceptive actions of systemically administered aliskerin in the writhing, formalin hindpaw, capsaicin-induced pain, post-operative pain, CCI-induced neuropathic pain and orofacial pain tests in mice. 35 A study from our laboratory has also reported the anti-hyperalgesic effect of spironolactone in diabetic neuropathic pain. 28 Spironolactone has also been shown to attenuate acetic acid-induced inflammatory visceral pain in mice.…”

Section: Preclinical Studiesmentioning

confidence: 99%

“…57 Studies have also documented the potent antiinflammatory potential of aliskerin by inhibiting leukocyte adhesion, preventing oxidative stress and decreasing the production of inflammatory cytokines, including interleukin(IL)-6 and TNF-α. 35,[58][59][60] Furthermore, aliskerin has also been shown to attenuate TNF-α-mediated deleterious effects on the different body systems. 60 Aliskerininduced decrease in inflammatory mediators may possibly be attributed to decrease in AngII levels.…”

Section: Possible Mechanismsmentioning

confidence: 99%

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Renin–angiotensin system in pain: Existing in a double life?

Bali

Singh

Jaggi

2014

J Renin Angiotensin Aldosterone Syst

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Apart from the well-documented role of the renin-angiotensin-aldosterone system (RAAS) in regulating the blood pressure and other related parameters, its role in modulating different physiological/pathological functions, including pain, has also been described. Like its dual role in regulating stress-related anxiety and cognitive functions, its dual role has also been documented in pain modulation in different disease states. Drugs blocking the RAAS activation, viz., renin inhibitors, angiotensin converting enzyme (ACE) inhibitors, AT 1 receptor antagonists and aldosterone antagonists, have been shown to produce beneficial effects in migraine and neuropathic and nociceptive pain. Their beneficial effects have been mainly attributed to inhibition of the inflammatory cascade of reactions by inhibiting the generation of key cytokines, including tumor necrosis factor (TNF)-α. On the contrary, clinical as well as preclinical studies have also shown the paininducing actions of renin-angiotensin system (RAS) blocking drugs. Furthermore, the pain-relieving actions of angiotensin II (AngII) and pain-inducing actions of AT 1 blockers have also been described. The pain-inducing actions of ACE inhibitors have been mainly attributed to interference with metabolism of bradykinin and substance P, while the analgesic actions of AngII have been mainly related to activation of brain localized AT 2 receptors and release of endogenous opioids. The present review describes the dual role of the RAAS in different states of pain.

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Section: Preclinical Studiesmentioning

confidence: 99%

Section: Possible Mechanismsmentioning

confidence: 99%

Renin–angiotensin system in pain: Existing in a double life?

Bali

Singh

Jaggi

2014

J Renin Angiotensin Aldosterone Syst

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“…Moreover, it has been demonstrated that many mediators are produced after the i.pl. injection of formaldehyde, including substance P, calcitonin gene-related peptide, histamine, serotonin, cytokines and eicosanoids Q4 (Damas and Liégeois, 1999;Dorazil-Dudzik et al, 2004;Hagains et al, 2010;Patel et al, 2013;Yamato et al, 2013;Wheeler-Aceto and Cowan, 1991). These mediators cause vasodilation and increased permeability, thus contributing to the development of edema.…”

Section: Discussionmentioning

confidence: 98%

Activities of 2-phthalimidethyl nitrate and 2-phthalimidethanol in the models of nociceptive response and edema induced by formaldehyde in mice and preliminary investigation of the underlying mechanisms

Godin

Araújo

César

et al. 2015

European Journal of Pharmacology

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“…Treatment times and doses of drugs were selected according to their biological activity reported earlier [e.g. ].…”

Section: Methodsmentioning

confidence: 99%

Effect of aliskiren, a direct renin inhibitor, on the protective action of antiepileptic drugs against pentylenetetrazole‐induced clonic seizures in mice

Łukawski

Raszewski

Czuczwar

2018

Fundamemntal Clinical Pharma

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It has been demonstrated that certain angiotensin‐converting enzyme (ACE) inhibitors and angiotensin AT1 receptor antagonists can possess anticonvulsant activity. The purpose of the current study was to examine the effect of aliskiren, a direct renin inhibitor and a novel antihypertensive drug, against pentylenetetrazole (PTZ)‐induced clonic seizures in mice and on the protective activity of conventional antiepileptic drugs (AEDs) in this seizure model. Effects of aliskiren on the PTZ threshold and the protective efficacy of AEDs, such as clonazepam (CLO), phenobarbital (PB), valproate (VPA), and ethosuximide (ETX) in the PTZ test, were evaluated in adult Swiss mice. Aliskiren and AEDs were administered intraperitoneally (i.p.) while PTZ (50–100 mg/kg) was injected subcutaneously (s.c.). The rota‐rod and passive avoidance test were used to assess the adverse effects of the combined treatment with aliskiren and AEDs. Aliskiren, at the dose of 75 mg/kg, significantly raised the PTZ threshold (P < 0.05). Furthermore, aliskiren, at the subthreshold dose of 50 mg/kg, significantly enhanced the protective action of CLO (P < 0.01), PB (P < 0.01), and VPA (P < 0.05) but not ETX (P > 0.05) in the s.c. PTZ test. Motor coordination in the rota‐rod test and long‐term memory in the passive avoidance task were not impaired by the combined treatment of the drugs. This study suggests that treatment with aliskiren can be useful in hypertensive patients with myoclonic seizures. Certainly, a clinical verification of using aliskiren in such patients would be necessary.

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Anti-nociceptive and anti-allodynic activity of aliskiren in various pain models

Cited by 13 publications

References 42 publications

Renin–angiotensin system in pain: Existing in a double life?

Renin–angiotensin system in pain: Existing in a double life?

Activities of 2-phthalimidethyl nitrate and 2-phthalimidethanol in the models of nociceptive response and edema induced by formaldehyde in mice and preliminary investigation of the underlying mechanisms

Effect of aliskiren, a direct renin inhibitor, on the protective action of antiepileptic drugs against pentylenetetrazole‐induced clonic seizures in mice

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