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

Hegazy, Nora; Rezq, Samar; Fahmy, Aly A.

doi:10.1111/bcpt.13453

Cited by 12 publications

(11 citation statements)

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“…Paw withdrawal latency was recorded in seconds. The brief normal response was given a value of 0.5 s and the cut-off point was set at 20 s (Hegazy et al, 2020).…”

Section: Mechanical Hyperalgesia (Pinprick Test)mentioning

confidence: 99%

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

et al. 2021

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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.

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“…Paw withdrawal latency was recorded in seconds. The brief normal response was given a value of 0.5 s and the cut-off point was set at 20 s (Hegazy et al, 2020).…”

Section: Mechanical Hyperalgesia (Pinprick Test)mentioning

confidence: 99%

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

et al. 2021

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“…Further, we investigated the antioxidant potential of both extracts in CCI model. Our previous studies showed that catalase is decreased while, NADPH oxidase-1 (NOX-1) is increased in sciatic nerve and brain stem of CCI rats 6,10,11 . Catalase enzyme is one of the endogenous antioxidant enzymes present in peroxisomes and catalyzes the breakdown of H 2 O 2 to H 2 O and O 2 .…”

Section: Discussionmentioning

confidence: 99%

“…. As detailed in our recent study 11 , a force was applied gently to the mid-plantar surface of the injured hind paw by bent gauge to avoid damaging the skin. Paw withdrawal duration (s) was recorded with a minimum value of 0.5 s (for the brief normal response) and a maximum value of 20 s.…”

Section: Mechanical Hyperalgesia (Pinprick Test)mentioning

confidence: 99%

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Thymus algeriensis and Thymus fontanesii exert neuroprotective effect against chronic constriction injury-induced neuropathic pain in rats

Rezq

Alsemeh

D’Elia

et al. 2020

Sci Rep

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We have previously demonstrated that the Thymus algeriensis and Thymus fontanesii extracts have powerful anti-inflammatory, antipyretic, and analgesic effects against acute pain models. We profiled their chemical composition and found many phenolic acids, flavonoids, and phenolic diterpenes. In this work, we investigated their antioxidant properties on HaCaT cells exposed to UVA-induced oxidative stress and examined their effects against chronic neuropathic pain and the underlying mechanisms. Through a rat chronic constriction injury (CCI) model, we induced chronic neuropathic pain by placing 4 loose ligatures around the right sciatic nerve for 14 days. Thermal and mechanical hyperalgesia in addition to cold and dynamic allodynia were tested on the day before surgery and on the 7th and 14th post-surgery days. Key markers of the nitrosative and oxidative stresses, in addition to markers of inflammation, were measured at day 14 post surgery. Histopathological examination and immunostaining of both synaptophysin and caspase-3 of sciatic nerve and brain stem were also performed. Results of this study showed that T. algeriensis extract suppresses UVA oxidative stress in HaCaT cells via activation of the Nrf-2 pathway. Both extracts attenuated hyperalgesia and allodynia at 7- and 14-days post-surgery with more prominent effects at day 14 of surgery. Their protective effects against neuropathic pain were mediated by inhibiting NOX-1, iNOS, by increasing the enzyme activity of catalase, and inhibition of inflammatory mediators, NF-κB, TNF-α, lipoxygenase, COX-2 enzymes, and PGE2. Furthermore, they improved deleterious structural changes of the brainstem and sciatic nerve. They also attenuated the increased caspase-3 and synaptophysin. The data indicate that both extracts have neuroprotective effects against chronic constriction injury-induced neuropathic pain. The observed protective effects are partially mediated through attenuation of oxidative and nitrosative stress and suppression of both neuroinflammation and neuronal apoptosis, suggesting substantial activities of both extracts in amelioration of painful peripheral neuropathy.

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“…Spontaneous paw lifting and flinching/licking were examined according to previous reports (Hegazy et al, 2020; Labuz & Machelska, 2013; Murai et al, 2016). In brief, a mouse was placed in an open‐topped transparent glass chamber and allowed to move freely for 20 min before being observed.…”

Section: Methodsmentioning

confidence: 99%

RALY participates in nerve trauma‐induced nociceptive hypersensitivity through triggering Eif4g2 gene expression in primary sensory neurons

Huang,

Sharma,

Feng

et al. 2023

British J Pharmacology

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Background and PurposePeripheral nerve trauma‐induced dysregulation of pain‐associated genes in the primary sensory neurons of dorsal root ganglion (DRG) contributes to neuropathic pain genesis. RNA‐binding proteins participate in gene transcription. We hypothesized that RALY, an RNA‐binding protein, participated in nerve trauma‐induced dysregulation of DRG pain‐associated genes and nociceptive hypersensitivity.Methods and ResultsImmunohistochemistry staining showed that RALY was expressed exclusively in the nuclei of DRG neurons. Peripheral nerve trauma caused by chronic constriction injury (CCI) of unilateral sciatic nerve produced time‐dependent increases in the levels of Raly mRNA and RALY protein in injured DRG. Blocking this increase through DRG microinjection of adeno‐associated virus 5 (AAV5)‐expressing Raly shRNA reduced the CCI‐induced elevation in the amount of eukaryotic initiation factor 4 gamma 2 (eIF4G2) mRNA and eIF4G2 protein in injured DRG and mitigated the development and maintenance of CCI‐induced nociceptive hypersensitivity, without altering basal (acute) response to noxious stimuli and locomotor activity. Mimicking DRG increased RALY through DRG microinjection of AAV5 expressing Raly mRNA upregulated the expression of eIF4G2 mRNA and eIF4G2 protein in the DRG and led to hypersensitive responses to noxious stimuli in the absence of nerve trauma. Mechanistically, CCI promoted the binding of RALY to the promoter of eIF4G2 gene and triggered its transcriptional activity.Conclusion and ImplicationsOur findings indicate that RALY participates in nerve trauma‐induced nociceptive hypersensitivity likely through transcriptionally triggering eIF4G2 expression in the DRG. RALY may be a potential target in neuropathic pain management.

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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

Cited by 12 publications

References 59 publications

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

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

Thymus algeriensis and Thymus fontanesii exert neuroprotective effect against chronic constriction injury-induced neuropathic pain in rats

RALY participates in nerve trauma‐induced nociceptive hypersensitivity through triggering Eif4g2 gene expression in primary sensory neurons

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