Activation of Neuroinflammation via mTOR Pathway is Disparately Regulated by Differential Target Multiplexed and Traditional Low-Rate Spinal Cord Stimulation in a Neuropathic Pain Model

References

• Gaskin DJ, Richard P. The economic costs of pain in the United States. J Pain. 2012;13:715–724. doi:10.1016/j.jpain.2012.03.009
   PubMed Web of Science ®Google Scholar
• Sommer C, Leinders M, Üçeyler N. Inflammation in the pathophysiology of neuropathic pain. Pain. 2018;159:595–602. doi:10.1097/j.pain.0000000000001122
   PubMed Web of Science ®Google Scholar
• Chakravarthy KV, Xing F, Bruno K, et al. A review of spinal and peripheral neuromodulation and neuroinflammation: lessons learned thus far and future prospects of biotype development. Neuromodulation. 2019;22:235–243. doi:10.1111/ner.12859
   PubMed Web of Science ®Google Scholar
• Obara I, Tochiki KK, Géranton SM, et al. Systemic inhibition of the mammalian target of rapamycin (mTOR) pathway reduces neuropathic pain in mice. Pain. 2011;152:2582–2595. doi:10.1016/j.pain.2011.07.025
   PubMed Web of Science ®Google Scholar
• Codeluppi S, Svensson CI, Hefferan MP, et al. The Rheb-mTOR pathway is upregulated in reactive astrocytes of the injured spinal cord. J Neurosci. 2009;29:1093–1104. doi:10.1523/JNEUROSCI.4103-08.2009
   PubMed Web of Science ®Google Scholar
• Kwon M, Han J, Kim UJ, et al. Inhibition of Mammalian Target of Rapamycin (mTOR) signaling in the insular cortex alleviates neuropathic pain after peripheral nerve injury. Front Mol Neurosci. 2017;10:79. doi:10.3389/fnmol.2017.00079
   PubMed Web of Science ®Google Scholar
• Li G, Lu X, Zhang S, Zhou Q, Zhang L. mTOR and Erk1/2 signaling in the cerebrospinal fluid-contacting nucleus is involved in neuropathic pain. Neurochem Res. 2015;40:1053–1062. doi:10.1007/s11064-015-1564-7
   PubMed Web of Science ®Google Scholar
• Zhang W, Sun XF, Bo JH, et al. Activation of mTOR in the spinal cord is required for pain hypersensitivity induced by chronic constriction injury in mice. Pharmacol Biochem Behav. 2013;111:64–70. doi:10.1016/j.pbb.2013.07.017
   PubMed Web of Science ®Google Scholar
• Ye X, Zhu M, Che X, et al. Lipopolysaccharide induces neuroinflammation in microglia by activating the MTOR pathway and downregulating Vps34 to inhibit autophagosome formation. J Neuroinflammation. 2020;17:18. doi:10.1186/s12974-019-1644-8
   PubMed Web of Science ®Google Scholar
• Deer TR, Mekhail N, Provenzano D, et al.; North R and Neuromodulation Appropriateness Consensus C. The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: the Neuromodulation Appropriateness Consensus Committee. Neuromodulation. 2014;17:515–550; discussion 550. doi:10.1111/ner.12208
   Web of Science ®Google Scholar
• Moriyama K, Murakawa K, Uno T, et al. A prospective, open-label, multicenter study to assess the efficacy of spinal cord stimulation and identify patients who would benefit. Neuromodulation. 2012;15:7–11; discussion 12. doi:10.1111/j.1525-1403.2011.00411.x
   PubMed Web of Science ®Google Scholar
• Vallejo R, Gupta A, Cedeno DL, et al. Clinical effectiveness and mechanism of action of spinal cord stimulation for treating chronic low back and lower extremity pain: a systematic review. Curr Pain Headache Rep. 2020;24:70. doi:10.1007/s11916-020-00907-2
   PubMed Web of Science ®Google Scholar
• Fishman M, Cordner H, Justiz R, et al. Twelve-Month results from multicenter, open-label, randomized controlled clinical trial comparing differential target multiplexed spinal cord stimulation and traditional spinal cord stimulation in subjects with chronic intractable back pain and leg pain. Pain Pract. 2021;21:912–923. doi:10.1111/papr.13066
   PubMed Web of Science ®Google Scholar
• Vallejo R, Kelley CA, Gupta A, Smith WJ, Vallejo A, Cedeno DL. Modulation of neuroglial interactions using differential target multiplexed spinal cord stimulation in an animal model of neuropathic pain. Mol Pain. 2020;16:1744806920918057. doi:10.1177/1744806920918057
   Web of Science ®Google Scholar
• Cedeno DL, Smith WJ, Kelley CA, Vallejo R. Spinal cord stimulation using differential target multiplexed programming modulates neural cell-specific transcriptomes in an animal model of neuropathic pain. Mol Pain. 2020;16:1744806920964360. doi:10.1177/1744806920964360
   Web of Science ®Google Scholar
• Smith WJ, Cedeño DL, Thomas SM, Kelley CA, Vetri F, Vallejo R. Modulation of microglial activation states by spinal cord stimulation in an animal model of neuropathic pain: comparing high rate, low rate, and differential target multiplexed programming. Mol Pain. 2021;17:1744806921999013. doi:10.1177/1744806921999013
   Web of Science ®Google Scholar
• Tilley DM, Cedeño DL, Vetri F, Platt DC, Vallejo R. Differential target multiplexed spinal cord stimulation programming modulates proteins involved in ion regulation in an animal model of neuropathic pain. Mol Pain. 2022;18:17448069211060181. doi:10.1177/17448069211060181
   Web of Science ®Google Scholar
• Cedeno DL, Tilley DM, Vetri F, Platt DC, Vallejo R. Proteomic and phosphoproteomic changes of MAPK-related inflammatory response in an animal model of neuropathic pain by differential target multiplexed SCS and low-rate SCS. J Pain Res. 2022;15:895–907. doi:10.2147/JPR.S348738
   PubMed Web of Science ®Google Scholar
• McAlister GC, Nusinow DP, Jedrychowski MP, et al. MultiNotch MS3 enables accurate, sensitive, and multiplexed detection of differential expression across cancer cell line proteomes. Anal Chem. 2014;86:7150–7158. doi:10.1021/ac502040v
   PubMed Web of Science ®Google Scholar
• Zhang L, Elias JE. Relative protein quantification using tandem mass tag mass spectrometry. Methods Mol Biol. 2017;1550:185–198. doi:10.1007/978-1-4939-6747-6_14
   PubMedGoogle Scholar
• Eng JK, McCormack AL, Yates JR. An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database. J Am Soc Mass Spectrom. 1994;5:976–989. doi:10.1016/1044-0305(94)80016-2
   PubMed Web of Science ®Google Scholar
• Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47:D607–D613. doi:10.1093/nar/gky1131
   PubMed Web of Science ®Google Scholar
• Thomas PD, Campbell MJ, Kejariwal A, et al. PANTHER: a library of protein families and subfamilies indexed by function. Genome Res. 2003;13:2129–2141. doi:10.1101/gr.772403
   PubMed Web of Science ®Google Scholar
• Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000;28:27–30. doi:10.1093/nar/28.1.27
   PubMed Web of Science ®Google Scholar
• Yue X, Schunter A, Hummon AB. Comparing multistep immobilized metal affinity chromatography and multistep TiO2 methods for phosphopeptide enrichment. Anal Chem. 2015;87:8837–8844. doi:10.1021/acs.analchem.5b01833
   PubMed Web of Science ®Google Scholar
• Laplante M, Sabatini DM. Regulation of mTORC1 and its impact on gene expression at a glance. J Cell Sci. 2013;126:1713–1719. doi:10.1242/jcs.125773
   PubMed Web of Science ®Google Scholar
• Lisi L, Aceto P, Navarra P, Dello Russo C. mTOR kinase: a possible pharmacological target in the management of chronic pain. Biomed Res Int. 2015;2015:394257. doi:10.1155/2015/394257
   PubMed Web of Science ®Google Scholar
• Bhaskar PT, Hay N. The two TORCs and Akt. Dev Cell. 2007;12:487–502. doi:10.1016/j.devcel.2007.03.020
   PubMed Web of Science ®Google Scholar
• Wu Y, Zhou BP. Kinases meet at TSC. Cell Res. 2007;17:971–973. doi:10.1038/cr.2007.106
   PubMed Web of Science ®Google Scholar
• Xu B, Liu SS, Wei J, et al. Role of spinal cord Akt-mTOR signaling pathways in postoperative hyperalgesia induced by plantar incision in mice. Front Neurosci. 2020;14:766. doi:10.3389/fnins.2020.00766
   PubMed Web of Science ®Google Scholar
• Cao M, Tan X, Jin W, et al. Upregulation of Ras homolog enriched in the brain (Rheb) in lipopolysaccharide-induced neuroinflammation. Neurochem Int. 2013;62:406–417. doi:10.1016/j.neuint.2013.01.025
   PubMed Web of Science ®Google Scholar
• Lasarge CL, Danzer SC. Mechanisms regulating neuronal excitability and seizure development following mTOR pathway hyperactivation. Front Mol Neurosci. 2014;7:18. doi:10.3389/fnmol.2014.00018
   PubMed Web of Science ®Google Scholar
• Meikle L, Talos DM, Onda H, et al. A mouse model of tuberous sclerosis: neuronal loss of Tsc1 causes dysplastic and ectopic neurons, reduced myelination, seizure activity, and limited survival. J Neurosci. 2007;27:5546–5558. doi:10.1523/JNEUROSCI.5540-06.2007
   PubMed Web of Science ®Google Scholar
• Zhang Y, Xu S, Liang KY, et al. Neuronal mTORC1 is required for maintaining the nonreactive state of astrocytes. J Biol Chem. 2017;292:100–111. doi:10.1074/jbc.M116.744482
   PubMed Web of Science ®Google Scholar
• Shih MH, Kao SC, Wang W, Yaster M, Tao YX. Spinal cord NMDA receptor-mediated activation of mammalian target of rapamycin is required for the development and maintenance of bone cancer-induced pain hypersensitivities in rats. J Pain. 2012;13:338–349. doi:10.1016/j.jpain.2011.12.006
   PubMed Web of Science ®Google Scholar
• Geranton SM, Jimenez-Diaz L, Torsney C, et al. A rapamycin-sensitive signaling pathway is essential for the full expression of persistent pain states. J Neurosci. 2009;29:15017–15027. doi:10.1523/JNEUROSCI.3451-09.2009
   PubMed Web of Science ®Google Scholar