Neuropathic pain-attenuating potential of aliskiren in chronic constriction injury model in rats

Abstract

The present study was designed to investigate the potential of aliskiren, a direct renin inhibitor, in chronic constriction injury (CCI)-induced neuropathic pain in rats. Neuropathic pain was induced by placing four loose ligatures around the sciatic nerve. Acetone drop, von Frey hair, pin-prick and hot plate tests were performed to assess cold allodynia, mechanical allodynia, mechanical and heat hyperalgesia, respectively. The levels of Tumor necrosis factor-alpha (TNFa) were measured in the sciatic nerve as an inflammatory marker. CCI was associated with the development of cold allodynia, mechanical allodynia, mechanical and heat hyperalgesia along with a rise in the levels of Tumor necrosis factoralpha (TNF-a). Administration of aliskiren (25 or 50 mg/kg intraperitoneal (i.p.)) for 14 days in CCI-subjected rats significantly attenuated CCI-induced pain-related behavior and rise in TNF-a level. It may be concluded that aliskiren-mediated anti-inflammatory actions may be responsible for its beneficial effects in neuropathic pain in rats.

Ameliorative potential of angiotensin-converting enzyme inhibitor (ramipril) on chronic constriction injury of sciatic nerve induced neuropathic pain in mice

“…11,14 RAAS mediated release of excess angiotensin II is a major culprit in the development of neuropathic pain sensitivity via angiotensin I and angiotensin II receptors. 17,20 Recent reports show that angiotensin I receptor blockers, i.e. telmisartan, produce an ameliorative effect against CCI-induced neuropathic pain.…”

“…Various pathological mechanisms and targets are explored in the development of CRPS in humans as well as experimental animals. 9 A recent study reported that RAAS plays a critical role in the management of neuropathic pain disorders, 17,19,21 as RAAS activation is due to the peripheral nerve injury associated with sympathetic outflow in secondary and tertiary neurons at spinal cord and dorsal root ganglion. 11,14 RAAS mediated release of excess angiotensin II is a major culprit in the development of neuropathic pain sensitivity via angiotensin I and angiotensin II receptors.…”

“…The reduction of angiotensin II may be beneficial in neurodegenerative disorders such as neuropathic pain, instead of angiotensin receptor blockers and renin inhibitors. 17,35 However, the role of ACE inhibitors has not yet been explored in the chronic constriction injury of sciatic nerve induced neuropathic pain model in mice. Therefore, the present study is focused to evaluate ramipril (ARTERE ® ; ACE inhibitor) in the management of chronic constriction injury-induced neuropathic pain in mice.…”

“…15,16 The RAAS modulators have been reported to ameliorate the neuropathic pain symptoms in various experimental animal models, i.e. aliskiren, a direct renin inhibitor; 17 , an angiotensin I receptor antagonist; 18 EMA401 and EMA300, an angiotensin II receptor antagonist; 19,20 and spironolactone, an aldosterone antagonist. 21 Angiotensin-converting enzyme (ACE) inhibitors enhance the bradykinin level and can cause the pain sensitivity via nociceptor (bradykinin receptor).…”

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

“…Administration of different doses of aliskerin (a direct renin inhibitor), telmisartan (AT 1 receptor antagonist with highest affinity) and spironolactone (aldosterone receptor antagonist) for 14 days attenuated neuropathic pain in terms of decrease in paw cold allodynia, mechanical allodynia and heat hyperalgesia in CCI-induced neuropathic pain in rats. 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.…”