Dose-related neuropathic and anti-neuropathic effects of simvastatin in vincristine-induced neuropathic pain in rats

Bhalla, Shrutya; Singh, Nirmal; Jaggi, Amteshwar Singh

doi:10.1016/j.fct.2015.02.016

Cited by 21 publications

(13 citation statements)

References 60 publications

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“…It demonstrates that simvastatin effect in reducing mechanical hyperalgesia had a particular profile in each time-point of the CRPS-I model. Dose-related effects of simvastatin were already seen in other neuropathic pain models ( Bhalla et al, 2015 ). These results are in agreement with studies in rodent models demonstrating that simvastatin ameliorated neuropathic pain ( Ohsawa et al, 2016 ) and blocked formalin-induced nociceptive behaviors in mice ( Chen et al, 2013 ).…”

Section: Discussionmentioning

confidence: 78%

Effects of Simvastatin Beyond Dyslipidemia: Exploring Its Antinociceptive Action in an Animal Model of Complex Regional Pain Syndrome-Type I

et al. 2017

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Simvastatin is a lipid-lowering agent that blocks the production of cholesterol through inhibition of 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase. In addition, recent evidence has suggested its anti-inflammatory and antinociceptive actions during inflammatory and pain disorders. Herein, we investigated the effects of simvastatin in an animal model of complex regional pain syndrome-type I, and its underlying mechanisms. Chronic post-ischemia pain (CPIP) was induced by ischemia and reperfusion (IR) injury of the left hind paw. Our findings showed that simvastatin inhibited mechanical hyperalgesia induced by CPIP model in single and repeated treatment schedules, respectively; however simvastatin did not alter inflammatory signs during CPIP model. The mechanisms underlying those actions are related to modulation of transient receptor potential (TRP) channels, especially TRMP8. Moreover, simvastatin oral treatment was able to reduce the nociception induced by acidified saline [an acid-sensing ion channels (ASICs) activator] and bradykinin (BK) stimulus, but not by TRPA1, TRPV1 or prostaglandin-E2 (PGE2). Relevantly, the antinociceptive effects of simvastatin did not seem to be associated with modulation of the descending pain circuits, especially noradrenergic, serotoninergic and dopaminergic systems. These results indicate that simvastatin consistently inhibits mechanical hyperalgesia during neuropathic and inflammatory disorders, possibly by modulating the ascending pain signaling (TRPM8/ASIC/BK pathways expressed in the primary sensory neuron). Thus, simvastatin open-up new standpoint in the development of innovative analgesic drugs for treatment of persistent pain, including CRPS-I.

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Section: Discussionmentioning

confidence: 78%

Effects of Simvastatin Beyond Dyslipidemia: Exploring Its Antinociceptive Action in an Animal Model of Complex Regional Pain Syndrome-Type I

et al. 2017

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“…Neuropathic pain: To induce neuropathic pain, the animals will be administered for 5 days with anintraperitoneally (i.p.) dose of vincristine of 0.1 mg/kg m.c, followed by two days with saline by the same route in the corresponding volume (Aley et al 1996, Bhalla et al 2015. This cycle will be repeated twice.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of efficacy and mechanisms of action of Cannabis sativa extracts with analgesic, anti-inflammatory and antiemetic properties in an in vivo model

Bartkowiak‐Wieczorek

Kamińska

Szulc

et al. 2017

JMS

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University of Medical Sciences participates in the realization of the project titled: „Development of the technology of producing cannabinoids from low THC hemp for use as preparations supporting treatment in oncological patients” awarded by the National Centre for Research and Development under project number: INNOMED/I/11/NCBR/2014. The duration of the grant is 36 months, and the total value of the grant is 28011845 PLN. The project is run by University of Life Sciences in Poznan. Laboratory of Experimental Pharmacogenetics at the Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences (PUMS) is realizing the task number 4 titled “Evaluation of efficacy and mechanisms of action of Cannabis sativa extracts with analgesic, anti-inflammatory and antiemetic properties in an in vivo model.” The aim of this project is the development of cannabinoid extract with reduced psychoactive component (THC), which due to its high content of cannabidiol (CBD) is meant to provide analgesic properties, and at the same time to reduce the risk of addiction and overdose. University of Medical Sciences is evaluating the analgesic, anti-inflammatory and antiemetic properties of the extract of Cannabis sativa in animal models coupled with neuropathic pain. Pharmacodynamic effects of plant extracts will be later assessed taking into account the level of selected genes and proteins expression.

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“…In contrast, animal studies generally report that statins reduce neuropathic pain. In a study of vincristine-induced neuropathic pain in rats, animals were treated with simvastatin 7.5, 15, or 30 mg/kg/day) for 14 days after receiving vincristine [57]. The lower doses of simvastatin (7.5 and 15 mg/kg/day) reversed the neuropathic pain and attenuated the vincristine-induced increase in myeloperoxidase activity but did not reduce cholesterol in the rats.…”

Section: The Paradox Of Statins and Neuropathic Painmentioning

confidence: 99%

“…In normal rats, higher doses of simvastatin (30 mg/kg/day) caused neuropathic pain. It has been proposed in this context that the absence of cholesterol is associated with neuropathic pain [57]. Further, there is an implication that the anti-inflammatory effects of the statin drug may reverse neuropathic pain even if there is no change in cholesterol [57].…”

Section: The Paradox Of Statins and Neuropathic Painmentioning

confidence: 99%

“…It has been proposed in this context that the absence of cholesterol is associated with neuropathic pain [57]. Further, there is an implication that the anti-inflammatory effects of the statin drug may reverse neuropathic pain even if there is no change in cholesterol [57]. In a murine chronic constrictive injury model, rosuvastatin reduced neuropathic pain and inflammation [58].…”

Section: The Paradox Of Statins and Neuropathic Painmentioning

confidence: 99%

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Statins and Neuropathic Pain: A Narrative Review

et al. 2020

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The frequently prescribed drug class of statins have pleiotropic effects and have been implicated in neuropathic pain syndromes. This narrative review examines studies of statin-induced neuropathic pain which to date have been conducted only in animal models. However, the pathophysiology of diabetic neuropathy in humans may shed some light on the etiology of neuropathic pain. Statins have exhibited a paradoxical effect in that statins appear to reduce neuropathic pain in animals but have been associated with neuropathic pain in humans. While there are certain postulated mechanisms offering elucidation as to how statins might be associated with neuropathic pain, there is, as the American Heart Association stated, to date no definitive association between statins and neuropathic pain. Statins are important drugs that reduce cardiovascular risk factors and should be prescribed to appropriate patients with these risk factors but some of this population is also at elevated risk for neuropathic pain from other causes.

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Dose-related neuropathic and anti-neuropathic effects of simvastatin in vincristine-induced neuropathic pain in rats

Cited by 21 publications

References 60 publications

Effects of Simvastatin Beyond Dyslipidemia: Exploring Its Antinociceptive Action in an Animal Model of Complex Regional Pain Syndrome-Type I

Effects of Simvastatin Beyond Dyslipidemia: Exploring Its Antinociceptive Action in an Animal Model of Complex Regional Pain Syndrome-Type I

Evaluation of efficacy and mechanisms of action of Cannabis sativa extracts with analgesic, anti-inflammatory and antiemetic properties in an in vivo model

Statins and Neuropathic Pain: A Narrative Review

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