MicroRNA-Based Delivery Systems for Chronic Neuropathic Pain Treatment in Dorsal Root Ganglion

Neuropathic pain is a significant global clinical issue that poses substantial challenges to both public health and the economy due to its complex underlying mechanisms. It has emerged as a serious health concern worldwide. Recent studies involving dorsal root ganglion (DRG) stimulation have provide...

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Main Authors: Stefan Jackson, Maria Rosa Gigliobianco, Cristina Casadidio, Piera Di Martino, Roberta Censi
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/7/930
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author Stefan Jackson
Maria Rosa Gigliobianco
Cristina Casadidio
Piera Di Martino
Roberta Censi
author_facet Stefan Jackson
Maria Rosa Gigliobianco
Cristina Casadidio
Piera Di Martino
Roberta Censi
author_sort Stefan Jackson
collection DOAJ
description Neuropathic pain is a significant global clinical issue that poses substantial challenges to both public health and the economy due to its complex underlying mechanisms. It has emerged as a serious health concern worldwide. Recent studies involving dorsal root ganglion (DRG) stimulation have provided strong evidence supporting its effectiveness in alleviating chronic pain and its potential for sustaining long-term pain relief. In addition to that, there has been ongoing research with clinical evidence relating to the role of small non-coding ribonucleic acids known as microRNAs in regulating gene expressions affecting pain signals. The signal pathway involves alterations in neuronal excitation, synaptic transmission, dysregulated signaling, and subsequent pro-inflammatory response activation and pain development. When microRNAs are dysregulated in the dorsal root ganglia neurons, they polarize macrophages from anti-inflammatory M2 to inflammatory M1 macrophages causing pain signal generation. By reversing this polarization, a therapeutic activity can be induced. However, the direct delivery of these nucleotides has been challenging due to limitations such as rapid clearance, degradation, and reduction in half-life. Therefore, safe and efficient carrier vehicles are fundamental for microRNA delivery. Here, we present a comprehensive analysis of miRNA-based nano-systems for chronic neuropathic pain, focusing on their impact in dorsal root ganglia. This review provides a critical evaluation of various delivery platforms, including viral, polymeric, lipid-based, and inorganic nanocarriers, emphasizing their therapeutic potential as well as their limitations in the treatment of chronic neuropathic pain. Innovative strategies such as hybrid nanocarriers and stimulus-responsive systems are also proposed to enhance the prospects for clinical translation. Serving as a roadmap for future research, this review aims to guide the development and optimization of miRNA-based therapies for effective and sustained neuropathic pain management.
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spelling doaj-art-e44eb2c8a9824ef1bad572cf32145ee72025-08-20T03:08:02ZengMDPI AGPharmaceutics1999-49232025-07-0117793010.3390/pharmaceutics17070930MicroRNA-Based Delivery Systems for Chronic Neuropathic Pain Treatment in Dorsal Root GanglionStefan Jackson0Maria Rosa Gigliobianco1Cristina Casadidio2Piera Di Martino3Roberta Censi4ChIP Chemistry Interdisciplinary Project Research Centre, School of Pharmacy, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, MC, ItalyDepartment of Pharmacy, “G. D’Annunzio” of Chieti and Pescara University, Via dei Vestini 1, 66100 Chieti, CH, ItalyChIP Chemistry Interdisciplinary Project Research Centre, School of Pharmacy, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, MC, ItalyDepartment of Pharmacy, “G. D’Annunzio” of Chieti and Pescara University, Via dei Vestini 1, 66100 Chieti, CH, ItalyChIP Chemistry Interdisciplinary Project Research Centre, School of Pharmacy, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, MC, ItalyNeuropathic pain is a significant global clinical issue that poses substantial challenges to both public health and the economy due to its complex underlying mechanisms. It has emerged as a serious health concern worldwide. Recent studies involving dorsal root ganglion (DRG) stimulation have provided strong evidence supporting its effectiveness in alleviating chronic pain and its potential for sustaining long-term pain relief. In addition to that, there has been ongoing research with clinical evidence relating to the role of small non-coding ribonucleic acids known as microRNAs in regulating gene expressions affecting pain signals. The signal pathway involves alterations in neuronal excitation, synaptic transmission, dysregulated signaling, and subsequent pro-inflammatory response activation and pain development. When microRNAs are dysregulated in the dorsal root ganglia neurons, they polarize macrophages from anti-inflammatory M2 to inflammatory M1 macrophages causing pain signal generation. By reversing this polarization, a therapeutic activity can be induced. However, the direct delivery of these nucleotides has been challenging due to limitations such as rapid clearance, degradation, and reduction in half-life. Therefore, safe and efficient carrier vehicles are fundamental for microRNA delivery. Here, we present a comprehensive analysis of miRNA-based nano-systems for chronic neuropathic pain, focusing on their impact in dorsal root ganglia. This review provides a critical evaluation of various delivery platforms, including viral, polymeric, lipid-based, and inorganic nanocarriers, emphasizing their therapeutic potential as well as their limitations in the treatment of chronic neuropathic pain. Innovative strategies such as hybrid nanocarriers and stimulus-responsive systems are also proposed to enhance the prospects for clinical translation. Serving as a roadmap for future research, this review aims to guide the development and optimization of miRNA-based therapies for effective and sustained neuropathic pain management.https://www.mdpi.com/1999-4923/17/7/930miRNAdorsal root gangliadrug deliverygene deliverybiomaterialspolymers
spellingShingle Stefan Jackson
Maria Rosa Gigliobianco
Cristina Casadidio
Piera Di Martino
Roberta Censi
MicroRNA-Based Delivery Systems for Chronic Neuropathic Pain Treatment in Dorsal Root Ganglion
Pharmaceutics
miRNA
dorsal root ganglia
drug delivery
gene delivery
biomaterials
polymers
title MicroRNA-Based Delivery Systems for Chronic Neuropathic Pain Treatment in Dorsal Root Ganglion
title_full MicroRNA-Based Delivery Systems for Chronic Neuropathic Pain Treatment in Dorsal Root Ganglion
title_fullStr MicroRNA-Based Delivery Systems for Chronic Neuropathic Pain Treatment in Dorsal Root Ganglion
title_full_unstemmed MicroRNA-Based Delivery Systems for Chronic Neuropathic Pain Treatment in Dorsal Root Ganglion
title_short MicroRNA-Based Delivery Systems for Chronic Neuropathic Pain Treatment in Dorsal Root Ganglion
title_sort microrna based delivery systems for chronic neuropathic pain treatment in dorsal root ganglion
topic miRNA
dorsal root ganglia
drug delivery
gene delivery
biomaterials
polymers
url https://www.mdpi.com/1999-4923/17/7/930
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