Peripheral Neuropathic Pain: From Experimental Models to Potential Therapeutic Targets in Dorsal Root Ganglion Neurons
Abstract
1. Introduction
1.1. Overview of Neuropathic Pain
1.2. Etiology and Patholoigcal Approches
2. Neuropathic Pain Models
2.1. Injury Induced
2.2. Systemic Exposure Neuropathic Pain Model
2.2.1. Resiniferatoxin
2.2.2. Acrylamide
2.2.3. Chemotherapy-Induced Peripheral Neuropathy (CIPN)
3. Molecular Targets in Dorsal Root Ganglia
3.1. Purinergic P2X Receptors (P2Xs)
3.1.1. Transient Receptor Potential Receptors
3.1.2. Voltage-Gated Sodium Channels (NaVs)
3.1.3. Voltage-Gated Calcium Channels
4. Epigenetic, Transcriptional, and Post-Translational Modification in Neuropathic Pain
4.1. DNA Methyltransferase (DNAMT) and Histone Deacetylase (HDAC)
4.1.1. DNA Methylation and Demethylation
4.1.2. Histone Deacetylase Inhibitors
4.2. p-ERK and Transcriptional Factors
4.3. Ubiquitination and Deubiquitination
5. Current Challenges to Manipulate on DRG in In Vivo Models
6. Conclusions
DRG | P2Xs | TRPs | NaVs | CaVs |
---|---|---|---|---|
Injury-Induced | ||||
SNL | P2X3 ↑ (IR: d7, mRNA: d1) [55,56,57] P2X3 ↓ (IR: d14, mRNA: d7) [55,57] P2X3—(IR: d3, mRNA: d14) [56] P2X4—(mRNA: d1, d7) [57] P2X5 ↑ (mRNA: d1, d7) [57] P2X6 ↓ (mRNA: d7) [57] P2X6—(mRNA: d1) [57] | TRPV1 ↑ (IR: d3, mRNA: d1-28) [56] TRPA1 ↑ (IR: d11, mRNA) [131] | NaV1.7 ↓ (L5, IR: d7, mRNA: d7) [132] NaV1.7 ↑ (L4, IR: d7, mRNA: d7) [132] NaV1.3 ↑ [133] NaV1.1 ↓ [133] NaV1.6 ↓ [133] NaV1.7 ↓ [133] NaV1.8 ↓ [133] NaV1.9 ↓ [133] | α2δ-1 subunit ↑ (mRNA: d2) [81] |
CCI | P2X2—(IR: d18) [134] P2X2 ↑ (mRNA: d14) [135] P2X3 ↑ (IR: d14, d18, mRNA: d14) [51,52,53,58,135] P2X4—(IR: d18) [134] P2X4 ↓ (IR:d18, mRNA: d14) [51,53] P2X5—(mRNA: d14) [134] P2X6—(IR: d18) [134] P2X6 ↑ (IR: d18) [53] | TRPM8 ↑ (IR: d4, d7, d10, d14, mRNA: d14) [64,136] TPRMP—(mRNA: d7) [136] TRPA1 ↑ (mRNA: d7, d14, d16) [136,137] TRPV1 ↑ (mRNA: d16) [137] TRPV1—(mRNA: d7, d14) [136] | NaV1.7 ↑ (IR: d7, mRNA: d7) [132] | α 1 ↓ (mRNA: d7) [82] |
SNI | P2X3—(IR: d7) [135] | TRPM8 ↓ [138] TRPV1 ↓ [138] TRPA1 ↓ [138] | Rats (protein) [139] NaV1.3 ↑ NaV1.7 ↓ NaV1.8 ↓ NaV1.9 ↓ Mice (mRNA) [140] NaV1.1 ↓ NaV1.2 − NaV1.3 ↓ NaV1.6 ↓ NaV1.7 ↓ NaV1.8 ↓ NaV1.9 ↓ | Cav3.2 ↑ [80] |
DRG | P2Xs | TRPs | NaVs | CaVs |
---|---|---|---|---|
Systemic Small Fiber Neuropathy | ||||
RTX | P2X3 ↑ (IR: d7) [59] | TRPV1 ↓ (mRNA: d3) [53,59,136] TRPA1 ↓ (mRNA: d3) [136,141] TRPM8—(mRNA: d3) [136] | N/A | N/A |
Cisplatin | P2X3 ↑ (mRNA: d14) [60] | TRPV1 ↑ [142] TRPA1 ↑ [142] TRPM8—[142] | N/A | CaV2.2 ↑ (IR: d3) [143] |
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Advantage | Disadvantage | Application | |
---|---|---|---|
SNL [21] | Specific injury in L5 and L6 DRG | Time consuming | Spinal nerve injection |
CCI [22] | Combine injury and uninjured fibers | Variation in each operation | Decompression model |
SNI [23] | Combine injury and uninjured fibers Robustness of the response | Low local inflammation |
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Yeh, T.-Y.; Luo, I.-W.; Hsieh, Y.-L.; Tseng, T.-J.; Chiang, H.; Hsieh, S.-T. Peripheral Neuropathic Pain: From Experimental Models to Potential Therapeutic Targets in Dorsal Root Ganglion Neurons. Cells 2020, 9, 2725. https://doi.org/10.3390/cells9122725
Yeh T-Y, Luo I-W, Hsieh Y-L, Tseng T-J, Chiang H, Hsieh S-T. Peripheral Neuropathic Pain: From Experimental Models to Potential Therapeutic Targets in Dorsal Root Ganglion Neurons. Cells. 2020; 9(12):2725. https://doi.org/10.3390/cells9122725
Chicago/Turabian StyleYeh, Ti-Yen, I-Wei Luo, Yu-Lin Hsieh, To-Jung Tseng, Hao Chiang, and Sung-Tsang Hsieh. 2020. "Peripheral Neuropathic Pain: From Experimental Models to Potential Therapeutic Targets in Dorsal Root Ganglion Neurons" Cells 9, no. 12: 2725. https://doi.org/10.3390/cells9122725
APA StyleYeh, T.-Y., Luo, I.-W., Hsieh, Y.-L., Tseng, T.-J., Chiang, H., & Hsieh, S.-T. (2020). Peripheral Neuropathic Pain: From Experimental Models to Potential Therapeutic Targets in Dorsal Root Ganglion Neurons. Cells, 9(12), 2725. https://doi.org/10.3390/cells9122725