Sigma-1 Receptors Control Neuropathic Pain and Peripheral Neuroinflammation After Nerve Injury in Female Mice: A Transcriptomic Study.
Artificial intelligence
Macrophage
Neuroinflammation
Neuropathic pain
Sigma-1 receptor
T cell
Journal
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
ISSN: 1557-1904
Titre abrégé: J Neuroimmune Pharmacol
Pays: United States
ID NLM: 101256586
Informations de publication
Date de publication:
20 Aug 2024
20 Aug 2024
Historique:
received:
20
12
2023
accepted:
05
08
2024
medline:
20
8
2024
pubmed:
20
8
2024
entrez:
20
8
2024
Statut:
epublish
Résumé
The mechanisms for neuropathic pain amelioration by sigma-1 receptor inhibition are not fully understood. We studied genome-wide transcriptomic changes (RNAseq) in the dorsal root ganglia (DRG) from wild-type and sigma-1 receptor knockout mice prior to and following Spared Nerve Injury (SNI). In wildtype mice, most of the transcriptomic changes following SNI are related to the immune function or neurotransmission. Immune function transcripts contain cytokines and markers for immune cells, including macrophages/monocytes and CD4 + T cells. Many of these immune transcripts were attenuated by sigma-1 knockout in response to SNI. Consistent with this we found, using flow cytometry, that sigma-1 knockout mice showed a reduction in macrophage/monocyte recruitment as well as an absence of CD4 + T cell recruitment in the DRG after nerve injury. Sigma-1 knockout mice showed a reduction of neuropathic (mechanical and cold) allodynia and spontaneous pain-like responses (licking of the injured paw) which accompany the decreased peripheral neuroinflammatory response after nerve injury. Treatment with maraviroc (a CCR5 antagonist which preferentially inhibits CD4 + T cells in the periphery) of neuropathic wild-type mice only partially replicated the sigma-1 knockout phenotype, as it did not alter cold allodynia but attenuated spontaneous pain-like responses and mechanical hypersensitivity. Therefore, modulation of peripheral CD4 + T cell activity might contribute to the amelioration of spontaneous pain and neuropathic tactile allodynia seen in the sigma-1 receptor knockout mice, but not to the effect on cold allodynia. We conclude that sigma-1 receptor inhibition decreases DRG neuroinflammation which might partially explain its anti-neuropathic effect.
Identifiants
pubmed: 39162886
doi: 10.1007/s11481-024-10144-8
pii: 10.1007/s11481-024-10144-8
doi:
Substances chimiques
Receptors, sigma
0
Sigma-1 Receptor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
46Subventions
Organisme : Ministerio de Universidades
ID : FPU16/03213
Organisme : Ministerio de Universidades
ID : FPU21/02736
Organisme : Junta de Andalucía
ID : CTS-109
Organisme : Junta de Andalucía
ID : CTS-109
Organisme : Junta de Andalucía
ID : CTS-109
Organisme : Junta de Andalucía
ID : CTS-109
Organisme : Junta de Andalucía
ID : CTS-109
Organisme : Junta de Andalucía
ID : CTS-109
Organisme : Junta de Andalucía
ID : CTS-109
Organisme : Junta de Andalucía
ID : CTS-109
Organisme : Ministerio de Ciencia e Innovación
ID : SAF2016-80540-R
Organisme : Ministerio de Ciencia e Innovación
ID : SAF2016-80540-R
Organisme : Universidad de Granada
ID : UCE-PP2017-05
Organisme : Universidad de Granada
ID : UCE-PP2017-05
Organisme : Agencia Estatal de Investigación
ID : 10.13039/501100011033
Organisme : Agencia Estatal de Investigación
ID : 10.13039/501100011033
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Asano K, Takahashi N, Ushiki M et al (2015) Intestinal CD169(+) macrophages initiate mucosal inflammation by secreting CCL8 that recruits inflammatory monocytes. Nat Commun 6:7802. https://doi.org/10.1038/NCOMMS8802
doi: 10.1038/NCOMMS8802
pubmed: 26193821
Bravo-Caparrós I, Perazzoli G, Yeste S et al (2019) Sigma-1 receptor inhibition reduces neuropathic pain induced by partial sciatic nerve transection in mice by opioid-dependent and -independent mechanisms. Front Pharmacol 10:613. https://doi.org/10.3389/FPHAR.2019.00613/BIBTEX
doi: 10.3389/FPHAR.2019.00613/BIBTEX
pubmed: 31263413
pmcid: 6584826
Bravo-Caparrós I, Ruiz-Cantero MC, Perazzoli G et al (2020) Sigma-1 receptors control neuropathic pain and macrophage infiltration into the dorsal root ganglion after peripheral nerve injury. FASEB J 34:5951–5966. https://doi.org/10.1096/FJ.201901921R
doi: 10.1096/FJ.201901921R
pubmed: 32157739
Cendán CM, Pujalte JM, Portillo-Salido E et al (2005) Formalin-induced pain is reduced in sigma(1) receptor knockout mice. Eur J Pharmacol 511:73–74. https://doi.org/10.1016/J.EJPHAR.2005.01.036
doi: 10.1016/J.EJPHAR.2005.01.036
pubmed: 15777781
Chen H, Jiang L, Zhang D et al (2022) Exploring the correlation between the Regulation of Macrophages by Regulatory T Cells and Peripheral Neuropathic Pain. Front Neurosci 16. https://doi.org/10.3389/FNINS.2022.813751
Cobos EJ, Nickerson CA, Gao F et al (2018) Mechanistic differences in Neuropathic Pain modalities revealed by correlating behavior with global expression profiling. Cell Rep 22:1301–1312. https://doi.org/10.1016/J.CELREP.2018.01.006
doi: 10.1016/J.CELREP.2018.01.006
pubmed: 29386116
pmcid: 5908229
Cortés-Montero E, Sánchez-Blázquez P, Onetti Y et al (2019) Ligands exert biased activity to regulate sigma 1 receptor interactions with cationic TRPA1, TRPV1, and TRPM8 channels. Front Pharmacol 10:634. https://doi.org/10.3389/FPHAR.2019.00634/BIBTEX
doi: 10.3389/FPHAR.2019.00634/BIBTEX
pubmed: 31249525
pmcid: 6582314
Costigan M, Belfer I, Griffin RS et al (2010) Multiple chronic pain states are associated with a common amino acid-changing allele in KCNS1. Brain 133:2519–2527. https://doi.org/10.1093/BRAIN/AWQ195
doi: 10.1093/BRAIN/AWQ195
pubmed: 20724292
pmcid: 2929335
Davis-Taber RA, Scott VES (2006) Transcriptional profiling of dorsal root ganglia in a neuropathic pain model using microarray and laser capture microdissection. Drug Dev Res 67:308–330. https://doi.org/10.1002/DDR.20096
doi: 10.1002/DDR.20096
de la Puente B, Nadal X, Portillo-Salido E et al (2009) Sigma-1 receptors regulate activity-induced spinal sensitization and neuropathic pain after peripheral nerve injury. Pain 145:294–303. https://doi.org/10.1016/J.PAIN.2009.05.013
doi: 10.1016/J.PAIN.2009.05.013
pubmed: 19505761
Decosterd I, Woolf CJ (2000) Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain 87:149–158. https://doi.org/10.1016/S0304-3959(00)00276-1
doi: 10.1016/S0304-3959(00)00276-1
pubmed: 10924808
Denaro S, Pasquinucci L, Turnaturi R et al (2023) Sigma-1 receptor inhibition reduces mechanical Allodynia and modulate Neuroinflammation in Chronic Neuropathic Pain. https://doi.org/10.1007/S12035-023-03717-W . Mol Neurobiol
Du X, Gamper N (2013) Potassium channels in peripheral pain pathways: expression, function and therapeutic potential. Curr Neuropharmacol 11:621–640. https://doi.org/10.2174/1570159X113119990042
doi: 10.2174/1570159X113119990042
pubmed: 24396338
pmcid: 3849788
Entrena JM, Cobos EJ, Nieto FR et al (2009) Sigma-1 receptors are essential for capsaicin-induced mechanical hypersensitivity: studies with selective sigma-1 ligands and sigma-1 knockout mice. Pain 143:252–261. https://doi.org/10.1016/J.PAIN.2009.03.011
doi: 10.1016/J.PAIN.2009.03.011
pubmed: 19375855
Ewels P, Magnusson M, Lundin S, Käller M (2016) MultiQC: summarize analysis results for multiple tools and samples in a single report. Bioinformatics 32:3047–3048. https://doi.org/10.1093/BIOINFORMATICS/BTW354
doi: 10.1093/BIOINFORMATICS/BTW354
pubmed: 27312411
pmcid: 5039924
Frankish A, Diekhans M, Jungreis I et al (2021) GENCODE 2021. Nucleic Acids Res 49:D916–D923. https://doi.org/10.1093/NAR/GKAA1087
doi: 10.1093/NAR/GKAA1087
pubmed: 33270111
Garvey L, Nelson M, Latch N et al (2012) CNS effects of a CCR5 inhibitor in HIV-infected subjects: a pharmacokinetic and cerebral metabolite study. J Antimicrob Chemother 67:206–212. https://doi.org/10.1093/JAC/DKR427
doi: 10.1093/JAC/DKR427
pubmed: 21987241
Ge B, Li J, Wei Z et al (2017) Functional expression of CCL8 and its interaction with chemokine receptor CCR3. BMC Immunol 18. https://doi.org/10.1186/S12865-017-0237-5
Ghazisaeidi S, Muley MM, Salter MW (2023) Neuropathic Pain: mechanisms, sex differences, and potential therapies for a global problem. Annu Rev Pharmacol Toxicol 63:565–583. https://doi.org/10.1146/ANNUREV-PHARMTOX-051421-112259
doi: 10.1146/ANNUREV-PHARMTOX-051421-112259
pubmed: 36662582
Gu Z, Eils R, Schlesner M (2016) Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32:2847–2849. https://doi.org/10.1093/BIOINFORMATICS/BTW313
doi: 10.1093/BIOINFORMATICS/BTW313
pubmed: 27207943
Gulick RM, Lalezari J, Goodrich J et al (2008) Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med 359:1429–1441. https://doi.org/10.1056/NEJMOA0803152
doi: 10.1056/NEJMOA0803152
pubmed: 18832244
pmcid: 3078519
Hall BE, Macdonald E, Cassidy M et al (2022) Transcriptomic analysis of human sensory neurons in painful diabetic neuropathy reveals inflammation and neuronal loss. Scientific Reports 2022 12:1 12:1–16. https://doi.org/10.1038/s41598-022-08100-8
Halvorsen EC, Hamilton MJ, Young A et al (2016) Maraviroc decreases CCL8-mediated migration of CCR5(+) regulatory T cells and reduces metastatic tumor growth in the lungs. Oncoimmunology 5:e1150398. https://doi.org/10.1080/2162402X.2016.1150398
doi: 10.1080/2162402X.2016.1150398
pubmed: 27471618
pmcid: 4938322
Horvath S, Zhang B, Carlson M et al (2006) Analysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular target. Proc Natl Acad Sci U S A 103:17402–17407. https://doi.org/10.1073/PNAS.0608396103
doi: 10.1073/PNAS.0608396103
pubmed: 17090670
pmcid: 1635024
Ino Y, Maruyama M, Shimizu M et al (2023) TSLP in DRG neurons causes the development of neuropathic pain through T cells. J Neuroinflammation 20. https://doi.org/10.1186/S12974-023-02882-Y
Ji RR, Xu ZZ, Gao YJ (2014) Emerging targets in neuroinflammation-driven chronic pain. Nat Rev Drug Discov 13:533–548. https://doi.org/10.1038/NRD4334
doi: 10.1038/NRD4334
pubmed: 24948120
pmcid: 4228377
Ji RR, Nackley A, Huh Y et al (2018) Neuroinflammation and Central Sensitization in chronic and widespread Pain. Anesthesiology 129:343–366. https://doi.org/10.1097/ALN.0000000000002130
doi: 10.1097/ALN.0000000000002130
pubmed: 29462012
Kim D, Paggi JM, Park C et al (2019) Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat Biotechnol 37:907–915. https://doi.org/10.1038/S41587-019-0201-4
doi: 10.1038/S41587-019-0201-4
pubmed: 31375807
pmcid: 7605509
Kwiatkowski K, Piotrowska A, Rojewska E et al (2016) Beneficial properties of maraviroc on neuropathic pain development and opioid effectiveness in rats. Prog Neuropsychopharmacol Biol Psychiatry 64:68–78. https://doi.org/10.1016/J.PNPBP.2015.07.005
doi: 10.1016/J.PNPBP.2015.07.005
pubmed: 26190414
Lacroix-Fralish ML, Austin JS, Zheng FY et al (2011) Patterns of pain: meta-analysis of microarray studies of pain. Pain 152:1888–1898. https://doi.org/10.1016/J.PAIN.2011.04.014
doi: 10.1016/J.PAIN.2011.04.014
pubmed: 21561713
Laedermann CJ, Pertin M, Suter MR, Decosterd I (2014) Voltage-gated sodium channel expression in mouse DRG after SNI leads to re-evaluation of projections of injured fibers. Mol Pain 10:19. https://doi.org/10.1186/1744-8069-10-19
doi: 10.1186/1744-8069-10-19
pubmed: 24618114
pmcid: 4007621
Langfelder P, Horvath S (2008) WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 9:559. https://doi.org/10.1186/1471-2105-9-559
doi: 10.1186/1471-2105-9-559
pubmed: 19114008
pmcid: 2631488
Li B, Dewey CN (2011) RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics 12:323. https://doi.org/10.1186/1471-2105-12-323
doi: 10.1186/1471-2105-12-323
pubmed: 21816040
pmcid: 3163565
Lindborg JA, Niemi JP, Howarth MA et al (2018) Molecular and cellular identification of the immune response in peripheral ganglia following nerve injury. J Neuroinflammation 15:192. https://doi.org/10.1186/S12974-018-1222-5
doi: 10.1186/S12974-018-1222-5
pubmed: 29945607
pmcid: 6019520
Love MI, Huber W, Anders S (2014) Moderated estimation of Fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15:550. https://doi.org/10.1186/S13059-014-0550-8
doi: 10.1186/S13059-014-0550-8
pubmed: 25516281
pmcid: 4302049
Lu Y, Jiang BC, Cao DL et al (2017) Chemokine CCL8 and its receptor CCR5 in the spinal cord are involved in visceral pain induced by experimental colitis in mice. Brain Res Bull 135:170–178. https://doi.org/10.1016/J.BRAINRESBULL.2017.10.009
doi: 10.1016/J.BRAINRESBULL.2017.10.009
pubmed: 29037608
Marcotti A, Fernández-Trillo J, González A et al (2023) TRPA1 modulation by Sigma-1 receptor prevents oxaliplatin-induced painful peripheral neuropathy. Brain 146:475–491. https://doi.org/10.1093/BRAIN/AWAC273
doi: 10.1093/BRAIN/AWAC273
pubmed: 35871491
Merlos M, Burgueño J, Portillo-Salido E et al (2017) Pharmacological modulation of the Sigma 1 receptor and the treatment of Pain. Adv Exp Med Biol 964:85–107. https://doi.org/10.1007/978-3-319-50174-1_8
doi: 10.1007/978-3-319-50174-1_8
pubmed: 28315267
Mogil JS, Graham AC, Ritchie J et al (2010) Hypolocomotion, asymmetrically directed behaviors (licking, lifting, flinching, and shaking) and dynamic weight bearing (gait) changes are not measures of neuropathic pain in mice. Mol Pain 6:34. https://doi.org/10.1186/1744-8069-6-34
doi: 10.1186/1744-8069-6-34
pubmed: 20529328
pmcid: 2893131
Montilla-García Á, Perazzoli G, Tejada M et al (2018) Modality-specific peripheral antinociceptive effects of µ-opioid agonists on heat and mechanical stimuli: contribution of sigma-1 receptors. Neuropharmacology 135:328–342. https://doi.org/10.1016/J.NEUROPHARM.2018.03.025
doi: 10.1016/J.NEUROPHARM.2018.03.025
pubmed: 29580951
Moon JY, Roh DH, Yoon SY et al (2014) σ1 receptors activate astrocytes via p38 MAPK phosphorylation leading to the development of mechanical allodynia in a mouse model of neuropathic pain. Br J Pharmacol 171:5881–5897. https://doi.org/10.1111/BPH.12893
doi: 10.1111/BPH.12893
pubmed: 25158784
pmcid: 4290724
Moon JY, Choi SR, Roh DH et al (2015) Spinal sigma-1 receptor activation increases the production of D-serine in astrocytes which contributes to the development of mechanical allodynia in a mouse model of neuropathic pain. Pharmacol Res 100:353–364. https://doi.org/10.1016/J.PHRS.2015.08.019
doi: 10.1016/J.PHRS.2015.08.019
pubmed: 26316425
Nair A, Jacob S (2016) A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm 7:27. https://doi.org/10.4103/0976-0105.177703
doi: 10.4103/0976-0105.177703
pubmed: 27057123
pmcid: 4804402
Ochoa-Callejero L, Pérez-Martínez L, Rubio-Mediavilla S et al (2013) Maraviroc, a CCR5 antagonist, prevents development of hepatocellular carcinoma in a mouse model. PLoS ONE 8:e53992. https://doi.org/10.1371/JOURNAL.PONE.0053992
doi: 10.1371/JOURNAL.PONE.0053992
pubmed: 23326556
pmcid: 3541191
Okonechnikov K, Conesa A, García-Alcalde F (2016) Qualimap 2: advanced multi-sample quality control for high-throughput sequencing data. Bioinformatics 32:292–294. https://doi.org/10.1093/BIOINFORMATICS/BTV566
doi: 10.1093/BIOINFORMATICS/BTV566
pubmed: 26428292
Pérez-Martínez L, Romero L, Muñoz-Galván S et al (2020) Implications of maraviroc and/or rapamycin in a mouse model of fragility. Aging 12:8565–8582. https://doi.org/10.18632/AGING.103167
doi: 10.18632/AGING.103167
pubmed: 32353830
pmcid: 7244075
Piotrowska A, Kwiatkowski K, Rojewska E et al (2016) Maraviroc reduces neuropathic pain through polarization of microglia and astroglia - evidence from in vivo and in vitro studies. Neuropharmacology 108:207–219. https://doi.org/10.1016/J.NEUROPHARM.2016.04.024
doi: 10.1016/J.NEUROPHARM.2016.04.024
pubmed: 27117708
Rosario MC, Jacqmin P, Dorr P et al (2008) Population pharmacokinetic/ pharmacodynamic analysis of CCR5 receptor occupancy by maraviroc in healthy subjects and HIV-positive patients. Br J Clin Pharmacol 65:86. https://doi.org/10.1111/J.1365-2125.2008.03140.X
doi: 10.1111/J.1365-2125.2008.03140.X
pubmed: 18333870
pmcid: 2311409
Ruffing N, Sullivan N, Sharmeen L et al (1998) CCR5 has an expanded ligand-binding repertoire and is the primary receptor used by MCP-2 on activated T cells. Cell Immunol 189:160–168. https://doi.org/10.1006/CIMM.1998.1379
doi: 10.1006/CIMM.1998.1379
pubmed: 9790730
Ruiz-Cantero MC, González-Cano R, Tejada M et al (2021) Sigma-1 receptor: a drug target for the modulation of neuroimmune and neuroglial interactions during chronic pain. Pharmacol Res 163:105339. https://doi.org/10.1016/J.PHRS.2020.105339
doi: 10.1016/J.PHRS.2020.105339
pubmed: 33276102
Ruiz-Cantero MC, Cortés-Montero E, Jain A et al (2023a) The sigma-1 receptor curtails endogenous opioid analgesia during sensitization of TRPV1 nociceptors. Br J Pharmacol 180:1148–1167. https://doi.org/10.1111/BPH.16003
doi: 10.1111/BPH.16003
pubmed: 36478100
Ruiz-Cantero MC, Huerta MÁ, Tejada MÁ et al (2023b) Sigma-1 receptor agonism exacerbates immune-driven nociception: role of TRPV1 + nociceptors. Biomed Pharmacother 167:115534. https://doi.org/10.1016/J.BIOPHA.2023.115534
doi: 10.1016/J.BIOPHA.2023.115534
pubmed: 37729726
Sánchez-Fernández C, Montilla-García Á, González-Cano R et al (2014) Modulation of peripheral µ-opioid analgesia by σ1 receptors. J Pharmacol Exp Ther 348:32–45. https://doi.org/10.1124/JPET.113.208272
doi: 10.1124/JPET.113.208272
pubmed: 24155346
Shin SM, Wang F, Qiu C et al (2022) Sigma-1 receptor activity in primary sensory neurons is a critical driver of neuropathic pain. Gene Ther 29:1–15. https://doi.org/10.1038/S41434-020-0157-5
doi: 10.1038/S41434-020-0157-5
pubmed: 32424233
Sorge RE, Mapplebeck JCS, Rosen S et al (2015) Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci 18:1081–1083. https://doi.org/10.1038/NN.4053
doi: 10.1038/NN.4053
pubmed: 26120961
pmcid: 4772157
Stanford WL, Haque S, Alexander R et al (1997) Altered proliferative response by T lymphocytes of Ly-6A (Sca-1) null mice. J Exp Med 186:705. https://doi.org/10.1084/JEM.186.5.705
doi: 10.1084/JEM.186.5.705
pubmed: 9271586
pmcid: 2199024
Tarazona S, García-Alcalde F, Dopazo J et al (2011) Differential expression in RNA-seq: a matter of depth. Genome Res 21:2213–2223. https://doi.org/10.1101/GR.124321.111
doi: 10.1101/GR.124321.111
pubmed: 21903743
pmcid: 3227109
Tsai S-Y, Hayashi T, Mori T, Su T-P (2009) Sigma-1 receptor chaperones and diseases. Cent Nerv Syst Agents Med Chem 9:184–189. https://doi.org/10.2174/1871524910909030184
doi: 10.2174/1871524910909030184
pubmed: 20021352
pmcid: 3150837
Vicuña L, Strochlic DE, Latremoliere A et al (2015) The serine protease inhibitor SerpinA3N attenuates neuropathic pain by inhibiting T cell-derived leukocyte elastase. Nat Med 21:518–523. https://doi.org/10.1038/NM.3852
doi: 10.1038/NM.3852
pubmed: 25915831
pmcid: 4450999
Vidal-Torres A, de la Puente B, Rocasalbas M et al (2013) Sigma-1 receptor antagonism as opioid adjuvant strategy: enhancement of opioid antinociception without increasing adverse effects. Eur J Pharmacol 711:63–72. https://doi.org/10.1016/J.EJPHAR.2013.04.018
doi: 10.1016/J.EJPHAR.2013.04.018
pubmed: 23632394
Wong GT (2002) Speed congenics: applications for transgenic and knock-out mouse strains. Neuropeptides 36:230–236. https://doi.org/10.1054/npep.2002.0905
doi: 10.1054/npep.2002.0905
pubmed: 12359513
Yokoyama H, Hirai T, Nagata T et al (2020) DNA microarray analysis of Differential Gene expression in the dorsal Root ganglia of four different neuropathic Pain Mouse models. J Pain Res 13:3031–3043. https://doi.org/10.2147/JPR.S272952
doi: 10.2147/JPR.S272952
pubmed: 33244261
pmcid: 7685567
Zheng Q, Xie W, Lückemeyer DD et al (2022) Synchronized cluster firing, a distinct form of sensory neuron activation, drives spontaneous pain. Neuron 110:209–220e6. https://doi.org/10.1016/J.NEURON.2021.10.019
doi: 10.1016/J.NEURON.2021.10.019
pubmed: 34752775
Zhu X, Cao S, Zhu M, Di et al (2014) Contribution of chemokine CCL2/CCR2 signaling in the dorsal root ganglion and spinal cord to the maintenance of neuropathic pain in a rat model of lumbar disc herniation. J Pain 15:516–526. https://doi.org/10.1016/J.JPAIN.2014.01.492
doi: 10.1016/J.JPAIN.2014.01.492
pubmed: 24462503