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

Abstract

Introduction: The present study was designed to investigate the effect of ramipril (angiotensin-converting enzyme inhibitor) on the chronic constriction injury of sciatic nerve induced neuropathic pain in mice. Methods: The neuropathic pain was induced by four loose ligations of the right sciatic nerve in mice. The battery of behavioral tests, i.e. plantar, pin prick, tail flick, tail pinch, rota rod tests, were performed to assess the degree of thermal and mechanical hyperalgesia in ipsilateral paw and tail, and motor in-coordination activity respectively. In addition, the biochemical tests, i.e. total protein, thiobarbituric acid reactive substances and reduced glutathione, were also performed in sciatic nerve tissue samples. Results: The administration of ramipril (2 and 4 mg/kg, p.o.) significantly attenuated chronic constriction injury-induced rise in peripheral as well as central pain sensitivity (thermal and mechanical) along with impairment of motor in-coordination activity. Further, it also produces ameliorative effects on chronic constriction injury-induced rise in thiobarbituric acid reactive substances and decrease in glutathione levels when compared with a normal control group. Conclusion: It may be concluded that angiotensin-converting enzyme inhibitor may be a potential new target for the management of neuropathic pain.

Ameliorative effect of gallic acid in paclitaxel-induced neuropathic pain in mice

“…In addition, PT also alters the neurovascular system leading to enhance the neuropathic pain symptoms [67]. Our recent findings revealed that alteration of a neuronal microvascular system is primary cardinal signs for the damage and degeneration of the nervous system [[68], [69], [70]]. Furthermore, some of our studies and other laboratory reports recommended that plant extracts and nutritional products of Acorus calamus [51,70], Butea monosperma [71], Swietenia mahagoni [72], Ocimum sanctum [73] and Vernonia cinerea [74] mitigate neuropathic pain symptoms.…”

Lack of association between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and pain improvement in patients with oral cancer

“…Contrarily, ramipril decreased the pain perception thresholds to ischaemic pain in humans and hypertensive rats as well as in those with neuropathic pain after constriction nerve injury, suggesting a potential analgesic effect of ACEis. [4,5,29] However, these medications did not have any impact on acute postsurgical pain in a large cohort of patients [30].…”

“…Previous studies indicate that ACEis and ARBs modulate important signalling mechanisms involved in inflammatory and neuropathic pain [4][5][6][7]. Pain is one of the most common complaints of patients with oral malignancies and can be present even before any cancer treatment has been initiated [8].…”

Renin‐angiotensin system blockade modulates both the peripheral and central components of neuropathic pain in rats: Role of calcitonin gene–related peptide, substance P and nitric oxide

“…A number of studies have previously reported the beneficial effect of renin‐angiotensin‐aldosterone system blockade in peripheral neuropathic pain 22,24,32 . Despite the involvement of CGRP, 7 SP 33 and NO 34 in the pathophysiology of NP and the ability of some renin‐angiotensin system blockers to modulate these neuromediators, 35,36 the intermediary role of CGRP, SP or NO in the neuroprotective effect of RAAS blockers in NP remains elusive.…”

“…), respectively, for 14 days. The doses used in this study were similar to those used in previous studies for enalapril, 19 losartan, 20,21 ramipril, 22 telmisartan 23,24 and pregabalin 22 . The sample size was calculated based on the need of the experiment using GraphPad StatMate 2 statistical program.…”