Analgesic and anti-inflammatory effects of modafinil in a mouse model of neuropathic pain: A role for nitrergic and serotonergic pathways: Modafinil & Neuropathic Pain. (4th May 2022)

• Record Type: Journal Article
• Authors: Ghorbanzadeh, Hossein; Mohebkhodaei, Parastoo; Nematizadeh, Mehran; Rahimi, Nastaran; Rafeiean, Mahsa; Ghasemi, Mehdi; Dehpour, Ahmad R.
• Is Part Of: Neurological research. Volume 44:Number 5(2022)
• Page Start: 390
• Page End: 402
• Publication Date: 2022-05-04
• Subjects: Modafinil -- neuropathic pain -- nitric oxide -- interleukin (il)-6 -- tumor necrosis factor (TNF)-α -- mice; Neurology -- Periodicals; Neurosciences -- Periodicals; 616.8005
• DOI: 10.1080/01616412.2021.1992102
• Languages: English
• ISSNs: 0161-6412

Abstract

ABSTRACT: Objectives: To evaluate the effects of modafinil on neuropathic pain induced by sciatic nerve cuffing in mice, and possible contribution of nitrergic/inflammatory and serotonergic systems. Methods: Neuropathic pain was induced by applying a polyethylene cuff around the left sciatic nerve. Seven days later, mice received modafinil (50, 100, and 200 mg/kg; intraperitoneal [i.p.]) and morphine (10 mg/kg, i.p.) as control. Mice also received pretreatments of the nonselective nitric oxide (NO) synthase (NOS) inhibitor L-NAME, the selective neuronal NOS inhibitor 7-nitroindazole, the selective inducible NOS inhibitor aminoguanidine, and the selective serotonin reuptake inhibitor citalopram before modafinil (100 mg/kg). von Frey test was used to evaluate mechanical allodynia. Additionally, sciatic nerves were collected for histopathological analysis. Tissue levels of NO metabolites, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were assessed. Results: Animals whose sciatic nerves were cuffed had a significantly ( P <0.001) decreased paw withdrawal threshold (PWT) compared with the sham-operated group. Modafinil (100 mg/kg) and morphine significantly reversed PWT ( P <0.001). Pretreatments with L-NAME, 7-nitroindazole, aminoguanidine, and citalopram in different groups markedly reversed analgesic effects of modafinil. Tissue homogenates of Cuffed sciatic nerves showed significantly higher levels of NO metabolites, TNF-α and IL-6 ( P <0.001). Modafinil lowered NO metabolites, TNF-α, and IL-6 levels ( P <0.001). Histopathology illustrated marked axonal degeneration and shrinkage in the cuffed sciatic nerve, which were improved in the modafinil-treated group. Conclusions: Modafinil exerts analgesic and neuroprotective effects in cuff-induced neuropathic mice via possible involvement of the nitrergic/inflammatory and serotonergic systems.