Hedging against Neuropathic Pain: Role of Hedgehog Signaling in Pathological Nerve Healing

Moreau, N.; Boucher, Yves

doi:10.3390/ijms21239115

Cited by 25 publications

(25 citation statements)

References 102 publications

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“…In this study, GSEA results showed that CHRNA3 was enriched in neuroactive ligand-receptor interaction, ECM-receptor interaction, and IL-17 signaling pathway-related pathways, while CHRNB2 and CHRNB4 were related to ferroptosis, the toll-like receptor signaling pathway, the hedgehog signaling pathway, cell cycle, the mTOR signaling pathway, and inflammatory mediator regulation of TRP channels, respectively. Most of these signaling pathways mediate nerve injury and the continuation of NPP by participating in neurotoxicity [ 31 ], neural activity [ 32 ], inflammatory response [ 33 , 34 ], hyperalgesia [ 35 ], nerve healing [ 36 , 37 ], microglia polarization [ 38 ], and oxidative stress [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…In this study, GSEA results showed that CHRNA3 was enriched in neuroactive ligandreceptor interaction, ECM-receptor interaction, and IL-17 signaling pathway-related pathways, while CHRNB2 and CHRNB4 were related to ferroptosis, the toll-like receptor signaling pathway, the hedgehog signaling pathway, cell cycle, the mTOR signaling pathway, and inflammatory mediator regulation of TRP channels, respectively. Most of these signaling pathways mediate nerve injury and the continuation of NPP by participating in neurotoxicity [31], neural activity [32], inflammatory response [33,34], hyperalgesia [35], nerve healing [36,37], microglia polarization [38], and oxidative stress [39]. e nicotine and nicotinic acetylcholine receptors (NAChRs) subtype, by a variety of subunits of combinatorial synthesis channel receptor complexes, its structure, and function in the nervous system of diversity, had been found to enhance the presynaptic neurotransmitter and release and affect the excitability of neurons, and when its function declines, it would cause the nervous system dysfunction [40,41].…”

Section: Discussionmentioning

confidence: 99%

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Application of Bioinformatics Methods to Identify Key Genes and Functions in Chronic Pelvic Pain

Sun

2021

Evidence-Based Complementary and Alternative Medicine

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Neuropathologic pain (NPP) occurs in most patients with chronic pelvic pain (CPP), and the unique physiological characteristics of visceral sensory neurons make the current analgesic effect of CPP patients not optimistic. Therefore, this study explored the possible biological characteristics of key genes in CPP through the bioinformatics method. CPP-related dataset GSE131619 was downloaded from Gene Expression Omnibus to investigate the differentially expressed genes (DEGs) between lumbar dorsal root ganglia (DRG) and sacral DRG, and the functional enrichment analysis was performed. A protein-protein interaction (PPI) network was constructed to search subnet modules of specific biological processes, and then, the genes in the subnet were enriched by single gene set analysis. A CPP mouse model was established, and the expression of key genes were identified by qPCR. The results showed that 127 upregulated DEGs and 103 downregulated DEGs are identified. Functional enrichment analysis showed that most of the genes involved in signal transduction were involved in the pathway of receptor interaction. A subnet module related to neural signal regulation was identified in PPI, including CHRNB4, CHRNA3, and CHRNB2. All three genes were associated with neurological or inflammatory activity and are downregulated in the sacral spinal cord of CPP mice. This study provided three key candidate genes for CPP: CHRNB4, CHRNA3, and CHRNB2, which may be involved in the occurrence and development of CPP, and provided a powerful molecular target for the clinical diagnosis and treatment of CPP.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Application of Bioinformatics Methods to Identify Key Genes and Functions in Chronic Pelvic Pain

Sun

2021

Evidence-Based Complementary and Alternative Medicine

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“…The most recently identified protein that appears to function in this way is Sonic hedgehog (Shh) (reviewed in Moreau and Boucher, 2020 ). Shh and Gli1, one of the downstream effectors of Shh signaling, are up-regulated in repair cells after injury, while Shh is also expressed in DRG neurons (Hashimoto et al, 2008 ; Arthur-Farraj et al, 2012 ; Martinez et al, 2015 ; Yamada et al, 2018 ).…”

Section: The Pharmacology Of Regeneration: Hijacking the Autocrine Lo...mentioning

confidence: 99%

The Role of c-Jun and Autocrine Signaling Loops in the Control of Repair Schwann Cells and Regeneration

Jessen

Mirsky

2022

Front. Cell. Neurosci.

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After nerve injury, both Schwann cells and neurons switch to pro-regenerative states. For Schwann cells, this involves reprogramming of myelin and Remak cells to repair Schwann cells that provide the signals and mechanisms needed for the survival of injured neurons, myelin clearance, axonal regeneration and target reinnervation. Because functional repair cells are essential for regeneration, it is unfortunate that their phenotype is not robust. Repair cell activation falters as animals get older and the repair phenotype fades during chronic denervation. These malfunctions are important reasons for the poor outcomes after nerve damage in humans. This review will discuss injury-induced Schwann cell reprogramming and the concept of the repair Schwann cell, and consider the molecular control of these cells with emphasis on c-Jun. This transcription factor is required for the generation of functional repair cells, and failure of c-Jun expression is implicated in repair cell failures in older animals and during chronic denervation. Elevating c-Jun expression in repair cells promotes regeneration, showing in principle that targeting repair cells is an effective way of improving nerve repair. In this context, we will outline the emerging evidence that repair cells are sustained by autocrine signaling loops, attractive targets for interventions aimed at promoting regeneration.

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“…The effectors of these pathways Sonic Hedgehog and Desert Hedgehog are involved in the nerve regeneration. Sonic Hedgehog initiates the neovascularization in the vicinity of the injured nerve to facilitate regeneration in diabetic rats [ 75 ]. A recent study demonstrated that the upregulation of microRNAs, miR-9 and miR-29a, leads to diabetic neuropathy and the painful symptoms.…”

Section: Metabolic Pathways Of Painful Diabetic Neuropathy (Pdn) and Potential Therapeutic Agentsmentioning

confidence: 99%

An Insight into Potential Pharmacotherapeutic Agents for Painful Diabetic Neuropathy

Qureshi

Ali

Khalid

2022

Journal of Diabetes Research

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Diabetes is the 4th most common disease affecting the world’s population. It is accompanied by many complications that deteriorate the quality of life. Painful diabetic neuropathy (PDN) is one of the debilitating consequences of diabetes that effects one-third of diabetic patients. Unfortunately, there is no internationally recommended drug that directly hinders the pathological mechanisms that result in painful diabetic neuropathy. Clinical studies have shown that anticonvulsant and antidepressant therapies have proven fruitful in management of pain associated with PDN. Currently, the FDA approved medications for painful diabetic neuropathies include duloxetine, pregabalin, tapentadol extended release, and capsaicin (for foot PDN only). The FDA has also approved the use of spinal cord stimulation system for the treatment of diabetic neuropathy pain. The drugs recommended by other regulatory bodies include gabapentin, amitriptyline, dextromethorphan, tramadol, venlafaxine, sodium valproate, and 5 % lidocaine patch. These drugs are only partially effective and have adverse effects associated with their use. Treating painful symptoms in diabetic patient can be frustrating not only for the patients but also for health care workers, so additional clinical trials for novel and conventional treatments are required to devise more effective treatment for PDN with minimal side effects. This review gives an insight on the pathways involved in the pathogenesis of PDN and the potential pharmacotherapeutic agents. This will be followed by an overview on the FDA-approved drugs for PDN and commercially available topical analgesic and their effects on painful diabetic neuropathies.

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Hedging against Neuropathic Pain: Role of Hedgehog Signaling in Pathological Nerve Healing

Cited by 25 publications

References 102 publications

Application of Bioinformatics Methods to Identify Key Genes and Functions in Chronic Pelvic Pain

Application of Bioinformatics Methods to Identify Key Genes and Functions in Chronic Pelvic Pain

The Role of c-Jun and Autocrine Signaling Loops in the Control of Repair Schwann Cells and Regeneration

An Insight into Potential Pharmacotherapeutic Agents for Painful Diabetic Neuropathy

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