Potamogeton perfoliatus L. Extract Attenuates Neuroinflammation and Neuropathic Pain in Sciatic Nerve Chronic Constriction Injury-Induced Peripheral Neuropathy in Rats.

Mona F Mahmoud,Samar Rezq,Mohamed A El Raey,Mohamed A O Abdelfattah,Rachid Daoud,Assem M El-Shazly,Amira E Alsemeh,Mansour Sobeh

doi:10.3389/fphar.2021.799444

Abstract

Sciatic nerve injury is often associated with neuropathic pain and neuroinflammation in the central and peripheral nervous systems. In our previous work, Potamogeton perfoliatus L. displayed anti-inflammatory, antipyretic and analgesic properties, predominantly via the inhibition of COX-2 enzyme and attenuation of oxidative stress. Herein, we extended our investigations to study the effects of the plant’s extract on pain-related behaviors, oxidative stress, apoptosis markers, GFAP, CD68 and neuro-inflammation in sciatic nerve chronic constriction injury (CCI) rat model. The levels of the pro-inflammatory marker proteins in sciatic nerve and brainstem were measured with ELISA 14 days after CCI induction. Pretreatment with the extract significantly attenuated mechanical and cold allodynia and heat hyperalgesia with better potential than the reference drug, pregabalin. In addition, CCI lead to the overexpression of prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), tumor necrosis alpha (TNFα), nuclear factor κB (NF-κB), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and NADPH oxidase-1 (NOX-1) and decreased the catalase level in sciatic nerve and brainstem. The observed neuro-inflammatory changes were accompanied with glial cells activation (increased GFAP and CD68 positive cells), apoptosis (increased Bax) and structural changes in both brainstem and sciatic nerve. The studied extract attenuated the CCI-induced neuro-inflammatory changes, oxidative stress, and apoptosis while it induced the expression of Bcl-2 and catalase in a dose dependent manner. It also decreased the brainstem expression of CD68 and GFAP indicating a possible neuroprotection effect. Taking together, P. perfoliatus may be considered as a novel therapy for neuropathic pain patients after performing the required clinical trials.

Highlights

Neuropathic pain is widely described as burning or electrical like sensation that affects mainly the areas sensitive to touch
We investigated the potential of a bioactive extract from P. perfoliatus to attenuate the neuropathic pain induced following a chronic constriction injury (CCI) in the sciatic nerve in rats via evaluating the hyperalgesia and allodynia symptoms
Our results showed that both pro-inflammatory mediators (TNF-α, nuclear factor κB (NF-κB) and prostaglandin E2 (PGE2)) and inflammatory enzymes, COX-2 and 5-LOX were increased in sciatic nerve and brainstem 14 days following the surgery

Summary

Introduction

Neuropathic pain is widely described as burning or electrical like sensation that affects mainly the areas sensitive to touch. Neuropathic pain is mainly caused by an ailment or a lesion in the somatosensory nervous system, which mediates the perception of temperature, pressure, pain, position, and touch (Costigan et al, 2009; Sobeh et al, 2019). Hyperalgesia and allodynia are two classic symptoms of neuropathic pain. The former is defined as an increased sensitivity towards a painful stimulus, while the later denotes a painful sensation to a stimulus that is normally non-painful (Zimmermann 2001; Sobeh et al, 2020). The symptoms of neuropathic pain are always manifested as excruciating pain aggravated upon pressure, pins and needles sensation, numbness, and difficulty in sensing temperatures properly (Woolf and Mannion, 1999)

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