位於周邊神經，背根神經節 (dorsal root ganglia，DRGs)及脊髓背角細胞(spinal dorsal horn，SDH)的各種不同發炎性介質，包含μ類鴉片受體 (mu-opioid receptor，MOR)、促炎性/抗炎性細胞素(pro-inflammatory/anti-inflammatory cytokine)、趨化素(chemokine)、小分子核糖核酸(microribonucleic acid，microRNA)和磷酸化-p38 (phospho-p38，p-p38) 在神經性疼痛的生成均伴有重要的角色。此外，細胞自噬(autophagy)及細胞凋亡(apoptosis)也調節了神經性疼痛的形成。顆粒性白血球群落刺激因子 (granulocyte colony-stimulating factor，G-CSF) 是一種生長因子，可刺激周邊血液中顆粒性白血球的形成，對神經性疼痛有鎮痛的作用。它是經由聚集含鴉片類物質的白血球到受損神經處，並抑制DRGs上的pro-inflammatory cytokine來達成止痛效果。此外，G-CSF也以多種方式對microRNA的表現、autophagy及apoptosis的活性產生影響。然而，G-CSF詳細的鎮痛機轉，以及pro-inflammatory cytokine、chemokine、microRNA、autophagy和apoptosis在慢性神經疼痛形成中的角色則尚未完全明瞭。因此，我們藉由動物疼痛行為測試，西方墨點法，酵素免疫分析法和免疫組織化學方法在神經損傷後的不同時間點（分別為神經損傷後1、3 和 7 天）分析假手術，接受與非接受G-CSF治療的慢性壓迫性神經損傷大鼠之受損周邊神經及DRGs上MOR、pro-inflammatory cytokine、chemokine、microRNA、autophagy和apoptosis蛋白質，及SDH上p-p38和pro-inflammatory cytokine的表現。結果顯示，在神經損傷後給予單次全身性的G-CSF治療後，可在神經受傷的初期促進受損周邊神經及DRGs上的MOR、microRNA-122、和細胞自噬蛋白質(autophagy protein: microtubule-associated protein light chain 3-II ，LC3II)的表達。然後這一系列的變化不但抑制了DRGs上的pro-inflammatory cytokine及chemokine (monocyte chemoattractant protein-1，MCP-1)的表現，並且在神經受傷的後期抑制了DRGs上的apoptosis蛋白質的表現，以及抑制SDH上的p-p38、pro-inflammatory cytokine (interleukin-6，IL-6) 的活性；唯增強了SDH上anti-inflammatory (interleukin-4，IL-4)的表現，藉此減輕神經性疼痛。因此，G-CSF 可以作為調節受損周邊神經、DRGs、SDH上pro-inflammatory cytokine、chemokine、microRNA、autophagy和apoptosis蛋白質表達的藥物，並進一步成為具有治療神經性疼痛潛力的藥物。然而，autophagy的神經性疼痛調節作用具有時間依賴性，必須在pro-inflammatory cytokine達到誘發神經性疼痛的閾值前的神經受傷初期階段，增加autophagy活性才可以有效抑制pro-inflammatory cytokine和apoptosis蛋白質的表達，藉此緩解神經性疼痛的進一步的發展。

The different inflammatory mediators including the mu-opioid receptor (MOR), pro-inflammatory/anti-inflammatory cytokines, chemokines, microribonucleic acid (microRNA), and phospho-p38 (p-p38) located on the peripheral nerves, the dorsal root ganglia (DRGs), and the spinal dorsal horn (SDH) have critical roles in neuropathic pain development. In addition to the previous agents, both autophagic and apoptotic activities can also modulate neuropathic pain formation. Granulocyte colony-stimulating factor (G-CSF) is a growth factor that can promote granulocyte production and has analgesic effects on neuropathic pain. The analgesic effects of G-CSF occur through recruiting leukocytes that secrete opioids to the injured nerve and suppressing pro-inflammatory cytokines in the DRGs. In addition, G-CSF can also modulate microRNA expressions, as well as autophagic and apoptotic activities in many ways. However, the detailed underlying analgesic mechanisms of G-CSF and the roles of pro-inflammatory cytokines, chemokines, microRNAs, autophagy, and apoptosis in chronic neuropathic pain formation are not fully understood. Therefore, mechanical allodynia, various levels of MORs, pro-inflammatory cytokines, chemokines, microRNAs, and apoptotic and autophagic proteins in the damaged sciatic nerves, and DRGs, p-p38, and different cytokine levels in the SDH were studied in the sham control. Rats with chronic constriction injuries received vehicle or G-CSF treatments at different times after nerve damage (1, 3, and 7 days) using Western blot analysis, enzyme-linked immunosorbent assays, and immunohistochemistry methods. The results demonstrated that a single intravenous dose of G-CSF immediately after nerve damage could increase MOR, microRNA-122, and autophagic protein (microtubule-associated protein light chain 3-II, LC3-II) expressions in the injured nerves and DRGs at an early time point after nerve damage. After that, those alterations suppressed pro-inflammatory cytokine and chemokine (monocyte chemoattractant protein-1, MCP-1) expressions and then suppressed the expressions of apoptotic proteins in the DRGs at a late time point after nerve damage. This further decreased p-p38 and pro-inflammatory cytokine (interleukin-6, IL-6) activities but enhanced anti-inflammatory cytokine (interleukin-4, IL-4) expressions in the SDH, and attenuated neuropathic pain. Thus, medications such as G-CSF could modulate the expressions of different pro-inflammatory cytokines, chemokines, microRNAs, and autophagic and apoptotic proteins in the injured nerve, DRGs, and SDH, which could potentially suppress neuropathic pain formation. However, this autophagy-mediated modulation of pain formation is time-dependent. Increased autophagy before pro-inflammatory cytokines reach the threshold level to promote neuropathic pain formation could effectively suppress pro-inflammatory cytokine expressions and apoptotic activities and alleviate the further development of neuropathic pain.

Allan, S. M., & Rothwell, N. J. (2001). Cytokines and acute neurodegeneration. Nat Rev Neurosci, 2(10), 734-744. https://doi.org/10.1038/35094583

Anderlini, P., Przepiorka, D., Champlin, R., & Korbling, M. (1996). Biologic and clinical effects of granulocyte colony-stimulating factor in normal individuals. Blood, 88(8), 2819-2825. http://www.ncbi.nlm.nih.gov/pubmed/8874177

Andersen, H. H., Duroux, M., & Gazerani, P. (2014). MicroRNAs as modulators and biomarkers of inflammatory and neuropathic pain conditions. Neurobiol Dis, 71, 159-168. https://doi.org/10.1016/j.nbd.2014.08.003

Arruda, J. L., Sweitzer, S., Rutkowski, M. D., & DeLeo, J. A. (2000). Intrathecal anti-IL-6 antibody and IgG attenuates peripheral nerve injury-induced mechanical allodynia in the rat: possible immune modulation in neuropathic pain. Brain Res, 879(1-2), 216-225. https://www.ncbi.nlm.nih.gov/pubmed/11011025

Baez, A., Martin-Antonio, B., Piruat, J. I., Prats, C., Alvarez-Laderas, I., Barbado, M. V., . . . Perez-Simon, J. A. (2014). Granulocyte colony-stimulating factor produces long-term changes in gene and microRNA expression profiles in CD34+ cells from healthy donors. Haematologica, 99(2), 243-251. https://doi.org/10.3324/haematol.2013.086959

Baldo, M. P., Davel, A. P., Damas-Souza, D. M., Nicoletti-Carvalho, J. E., Bordin, S., Carvalho, H. F., . . . Mill, J. G. (2011). The antiapoptotic effect of granulocyte colony-stimulating factor reduces infarct size and prevents heart failure development in rats. Cell Physiol Biochem, 28(1), 33-40. https://doi.org/10.1159/000331711

Bali, K. K., & Kuner, R. (2014). Noncoding RNAs: key molecules in understanding and treating pain. Trends Mol Med, 20(8), 437-448. https://doi.org/10.1016/j.molmed.2014.05.006

Bartel, D. P. (2009). MicroRNAs: target recognition and regulatory functions. Cell, 136(2), 215-233. https://doi.org/10.1016/j.cell.2009.01.002

Basbaum, A. I., Bautista, D. M., Scherrer, G., & Julius, D. (2009). Cellular and molecular mechanisms of pain. Cell, 139(2), 267-284. https://doi.org/10.1016/j.cell.2009.09.028

Bennett, G. J., & Xie, Y. K. (1988). A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain, 33(1), 87-107. https://doi.org/10.1016/0304-3959(88)90209-6

Berliocchi, L., Russo, R., Maiaru, M., Levato, A., Bagetta, G., & Corasaniti, M. T. (2011). Autophagy impairment in a mouse model of neuropathic pain. Mol Pain, 7, 83. https://doi.org/10.1186/1744-8069-7-83

Biasizzo, M., & Kopitar-Jerala, N. (2020). Interplay Between NLRP3 Inflammasome and Autophagy. Front Immunol, 11, 591803. https://doi.org/10.3389/fimmu.2020.591803

Brandenburger, T., Johannsen, L., Prassek, V., Kuebart, A., Raile, J., Wohlfromm, S., . . . Hermanns, H. (2019). MiR-34a is differentially expressed in dorsal root ganglia in a rat model of chronic neuropathic pain. Neurosci Lett, 708, 134365. https://doi.org/10.1016/j.neulet.2019.134365

Bussi, C., Peralta Ramos, J. M., Arroyo, D. S., Gaviglio, E. A., Gallea, J. I., Wang, J. M., . . . Iribarren, P. (2017). Autophagy down regulates pro-inflammatory mediators in BV2 microglial cells and rescues both LPS and alpha-synuclein induced neuronal cell death. Sci Rep, 7, 43153. https://doi.org/10.1038/srep43153

Cai, W., Zhang, Y., & Su, Z. (2020). ciRS-7 targeting miR-135a-5p promotes neuropathic pain in CCI rats via inflammation and autophagy. Gene, 736, 144386. https://doi.org/10.1016/j.gene.2020.144386

Cai, W., Zhao, Q., Shao, J., Zhang, J., Li, L., Ren, X., . . . Zang, W. (2018). MicroRNA-182 Alleviates Neuropathic Pain by Regulating Nav1.7 Following Spared Nerve Injury in Rats. Sci Rep, 8(1), 16750. https://doi.org/10.1038/s41598-018-34755-3

Campana, W. M., & Myers, R. R. (2003). Exogenous erythropoietin protects against dorsal root ganglion apoptosis and pain following peripheral nerve injury. Eur J Neurosci, 18(6), 1497-1506. https://doi.org/10.1046/j.1460-9568.2003.02875.x

Cao, Z., Wang, Y., Long, Z., & He, G. (2019). Interaction between autophagy and the NLRP3 inflammasome. Acta Biochim Biophys Sin (Shanghai), 51(11), 1087-1095. https://doi.org/10.1093/abbs/gmz098

Chao, P. K., Lu, K. T., Lee, Y. L., Chen, J. C., Wang, H. L., Yang, Y. L., . . . Ro, L. S. (2012). Early systemic granulocyte-colony stimulating factor treatment attenuates neuropathic pain after peripheral nerve injury. PLoS One, 7(8), e43680. https://doi.org/10.1371/journal.pone.0043680

Chen, H. P., Zhou, W., Kang, L. M., Yan, H., Zhang, L., Xu, B. H., & Cai, W. H. (2014). Intrathecal miR-96 inhibits Nav1.3 expression and alleviates neuropathic pain in rat following chronic construction injury. Neurochem Res, 39(1), 76-83. https://doi.org/10.1007/s11064-013-1192-z

Chen, R., Yin, C., Fang, J., & Liu, B. (2021). The NLRP3 inflammasome: an emerging therapeutic target for chronic pain. J Neuroinflammation, 18(1), 84. https://doi.org/10.1186/s12974-021-02131-0

Chen, W., & Lu, Z. (2017). Upregulated TLR3 Promotes Neuropathic Pain by Regulating Autophagy in Rat With L5 Spinal Nerve Ligation Model. Neurochem Res, 42(2), 634-643. https://doi.org/10.1007/s11064-016-2119-2

Chen, W. F., Jean, Y. H., Sung, C. S., Wu, G. J., Huang, S. Y., Ho, J. T., . . . Wen, Z. H. (2008). Intrathecally injected granulocyte colony-stimulating factor produced neuroprotective effects in spinal cord ischemia via the mitogen-activated protein kinase and Akt pathways. Neuroscience, 153(1), 31-43. https://doi.org/10.1016/j.neuroscience.2008.01.062

Chen, X. J., Wang, L., & Song, X. Y. (2020). Mitoquinone alleviates vincristine-induced neuropathic pain through inhibiting oxidative stress and apoptosis via the improvement of mitochondrial dysfunction. Biomed Pharmacother, 125, 110003. https://doi.org/10.1016/j.biopha.2020.110003

Cheng, X. P., Wang, B. R., Liu, H. L., You, S. W., Huang, W. J., Jiao, X. Y., & Ju, G. (2003). Phosphorylation of extracellular signal-regulated kinases 1/2 is predominantly enhanced in the microglia of the rat spinal cord following dorsal root transection. Neuroscience, 119(3), 701-712. https://doi.org/10.1016/s0306-4522(03)00035-6

Ciaccio, M. F., Wagner, J. P., Chuu, C. P., Lauffenburger, D. A., & Jones, R. B. (2010). Systems analysis of EGF receptor signaling dynamics with microwestern arrays. Nat Methods, 7(2), 148-155. https://doi.org/10.1038/nmeth.1418

Cobb, M. H. (1999). MAP kinase pathways. Prog Biophys Mol Biol, 71(3-4), 479-500. https://doi.org/10.1016/s0079-6107(98)00056-x

Coggeshall, R. E., Zhou, S., & Carlton, S. M. (1997). Opioid receptors on peripheral sensory axons. Brain Res, 764(1-2), 126-132. https://doi.org/10.1016/s0006-8993(97)00446-0

Crown, E. D. (2012). The role of mitogen activated protein kinase signaling in microglia and neurons in the initiation and maintenance of chronic pain. Exp Neurol, 234(2), 330-339. https://doi.org/10.1016/j.expneurol.2011.10.019

Di Cesare Mannelli, L., Ghelardini, C., Calvani, M., Nicolai, R., Mosconi, L., Toscano, A., . . . Bartolini, A. (2009). Neuroprotective effects of acetyl-L-carnitine on neuropathic pain and apoptosis: a role for the nicotinic receptor. J Neurosci Res, 87(1), 200-207. https://doi.org/10.1002/jnr.21815

Elmore, S. (2007). Apoptosis: a review of programmed cell death. Toxicol Pathol, 35(4), 495-516. https://doi.org/10.1080/01926230701320337

Elramah, S., Landry, M., & Favereaux, A. (2014). MicroRNAs regulate neuronal plasticity and are involved in pain mechanisms. Front Cell Neurosci, 8, 31. https://doi.org/10.3389/fncel.2014.00031

Fu, H., Li, F., Thomas, S., & Yang, Z. (2017). Hyperbaric oxygenation alleviates chronic constriction injury (CCI)-induced neuropathic pain and inhibits GABAergic neuron apoptosis in the spinal cord. Scand J Pain, 17, 330-338. https://doi.org/10.1016/j.sjpain.2017.08.014

Fuste, B., Mazzara, R., Escolar, G., Merino, A., Ordinas, A., & Diaz-Ricart, M. (2004). Granulocyte colony-stimulating factor increases expression of adhesion receptors on endothelial cells through activation of p38 MAPK. Haematologica, 89(5), 578-585. http://www.ncbi.nlm.nih.gov/pubmed/15136221

Ge, Y., Huang, M., & Yao, Y. M. (2018). Autophagy and proinflammatory cytokines: Interactions and clinical implications. Cytokine Growth Factor Rev, 43, 38-46. https://doi.org/10.1016/j.cytogfr.2018.07.001

Geiss, G. K., Bumgarner, R. E., Birditt, B., Dahl, T., Dowidar, N., Dunaway, D. L., . . . Dimitrov, K. (2008). Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol, 26(3), 317-325. https://doi.org/10.1038/nbt1385

Gissen, A. J., Gugino, L. D., Datta, S., Miller, J., & Covino, B. G. (1987). Effects of fentanyl and sufentanil on peripheral mammalian nerves. Anesth Analg, 66(12), 1272-1276. http://www.ncbi.nlm.nih.gov/pubmed/2961289

Glick, D., Barth, S., & Macleod, K. F. (2010). Autophagy: cellular and molecular mechanisms. J Pathol, 221(1), 3-12. https://doi.org/10.1002/path.2697

Gold, M. S., & Levine, J. D. (1996). DAMGO inhibits prostaglandin E2-induced potentiation of a TTX-resistant Na+ current in rat sensory neurons in vitro. Neurosci Lett, 212(2), 83-86. http://www.ncbi.nlm.nih.gov/pubmed/8832644

Gomez-Sanchez, J. A., Carty, L., Iruarrizaga-Lejarreta, M., Palomo-Irigoyen, M., Varela-Rey, M., Griffith, M., . . . Jessen, K. R. (2015). Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves. J Cell Biol, 210(1), 153-168. https://doi.org/10.1083/jcb.201503019

Grace, P. M., Hutchinson, M. R., Maier, S. F., & Watkins, L. R. (2014). Pathological pain and the neuroimmune interface. Nat Rev Immunol, 14(4), 217-231. https://doi.org/10.1038/nri3621

Gump, J. M., & Thorburn, A. (2011). Autophagy and apoptosis: what is the connection? Trends Cell Biol, 21(7), 387-392. https://doi.org/10.1016/j.tcb.2011.03.007

Guo, J. B., Zhu, Y., Chen, B. L., Song, G., Peng, M. S., Hu, H. Y., . . . Wang, X. Q. (2019). Network and pathway-based analysis of microRNA role in neuropathic pain in rat models. J Cell Mol Med, 23(7), 4534-4544. https://doi.org/10.1111/jcmm.14357

Guo, J. S., Jing, P. B., Wang, J. A., Zhang, R., Jiang, B. C., Gao, Y. J., & Zhang, Z. J. (2015). Increased autophagic activity in dorsal root ganglion attenuates neuropathic pain following peripheral nerve injury. Neurosci Lett, 599, 158-163. https://doi.org/10.1016/j.neulet.2015.05.046

Guo, Y., Liu, S., Zhang, X., Wang, L., Gao, J., Han, A., & Hao, A. (2015). G-CSF promotes autophagy and reduces neural tissue damage after spinal cord injury in mice. Lab Invest, 95(12), 1439-1449. https://doi.org/10.1038/labinvest.2015.120

Harris, J. (2013). Autophagy and IL-1 Family Cytokines. Front Immunol, 4, 83. https://doi.org/10.3389/fimmu.2013.00083

He, L., & Hannon, G. J. (2004). MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet, 5(7), 522-531. https://doi.org/10.1038/nrg1379

Heinke, B., Gingl, E., & Sandkuhler, J. (2011). Multiple targets of mu-opioid receptor-mediated presynaptic inhibition at primary afferent Adelta- and C-fibers. J Neurosci, 31(4), 1313-1322. https://doi.org/10.1523/JNEUROSCI.4060-10.2011

Hu, Q., Fang, L., Li, F., Thomas, S., & Yang, Z. (2015). Hyperbaric oxygenation treatment alleviates CCI-induced neuropathic pain and decreases spinal apoptosis. Eur J Pain, 19(7), 920-928. https://doi.org/10.1002/ejp.618

Huang, H. C., Chen, L., Zhang, H. X., Li, S. F., Liu, P., Zhao, T. Y., & Li, C. X. (2016). Autophagy Promotes Peripheral Nerve Regeneration and Motor Recovery Following Sciatic Nerve Crush Injury in Rats. J Mol Neurosci, 58(4), 416-423. https://doi.org/10.1007/s12031-015-0672-9

Huang, P., Chen, C., Mague, S. D., Blendy, J. A., & Liu-Chen, L. Y. (2012). A common single nucleotide polymorphism A118G of the mu opioid receptor alters its N-glycosylation and protein stability. Biochem J, 441(1), 379-386. https://doi.org/10.1042/BJ20111050

Inoue, K., & Tsuda, M. (2009). Microglia and neuropathic pain. Glia, 57(14), 1469-1479. https://doi.org/10.1002/glia.20871

Jacobs, J. M., & Ro, L. S. (1994). A morphological study of experimental mononeuropathy in the rat: early ischemic changes. J Neurol Sci, 127(2), 143-152. https://www.ncbi.nlm.nih.gov/pubmed/7707073

Jaffe, R. A., & Rowe, M. A. (1996). A comparison of the local anesthetic effects of meperidine, fentanyl, and sufentanil on dorsal root axons. Anesth Analg, 83(4), 776-781. https://doi.org/10.1097/00000539-199610000-00021

Jang, S. Y., Shin, Y. K., Park, S. Y., Park, J. Y., Lee, H. J., Yoo, Y. H., . . . Park, H. T. (2016). Autophagic myelin destruction by Schwann cells during Wallerian degeneration and segmental demyelination. Glia, 64(5), 730-742. https://doi.org/10.1002/glia.22957

Jeon, S. M., Lee, K. M., & Cho, H. J. (2009). Expression of monocyte chemoattractant protein-1 in rat dorsal root ganglia and spinal cord in experimental models of neuropathic pain. Brain Res, 1251, 103-111. https://doi.org/10.1016/j.brainres.2008.11.046

Jeon, S. M., Lee, K. M., Park, E. S., Jeon, Y. H., & Cho, H. J. (2008). Monocyte chemoattractant protein-1 immunoreactivity in sensory ganglia and hindpaw after adjuvant injection. Neuroreport, 19(2), 183-186. https://doi.org/10.1097/WNR.0b013e3282f3c781

Ji, R. R., & Suter, M. R. (2007). p38 MAPK, microglial signaling, and neuropathic pain. Mol Pain, 3, 33. https://doi.org/10.1186/1744-8069-3-33

Ji, R. R., & Woolf, C. J. (2001). Neuronal plasticity and signal transduction in nociceptive neurons: implications for the initiation and maintenance of pathological pain. Neurobiol Dis, 8(1), 1-10. https://doi.org/10.1006/nbdi.2000.0360

Jin, S. X., Zhuang, Z. Y., Woolf, C. J., & Ji, R. R. (2003). p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain. J Neurosci, 23(10), 4017-4022. https://www.ncbi.nlm.nih.gov/pubmed/12764087

Jopling, C. (2012). Liver-specific microRNA-122: Biogenesis and function. RNA Biol, 9(2), 137-142. https://doi.org/10.4161/rna.18827

Joseph, E. K., & Levine, J. D. (2004). Caspase signalling in neuropathic and inflammatory pain in the rat. Eur J Neurosci, 20(11), 2896-2902. https://doi.org/10.1111/j.1460-9568.2004.03750.x

Jung, H., Toth, P. T., White, F. A., & Miller, R. J. (2008). Monocyte chemoattractant protein-1 functions as a neuromodulator in dorsal root ganglia neurons. J Neurochem, 104(1), 254-263. https://doi.org/10.1111/j.1471-4159.2007.04969.x

Jung, K. T., & Lim, K. J. (2015). Autophagy: Can It be a New Experimental Research Method of Neuropathic Pain? Korean J Pain, 28(4), 229-230. https://doi.org/10.3344/kjp.2015.28.4.229

Kato, K., Koda, M., Takahashi, H., Sakuma, T., Inada, T., Kamiya, K., . . . Furuya, T. (2015). Granulocyte colony-stimulating factor attenuates spinal cord injury-induced mechanical allodynia in adult rats. J Neurol Sci, 355(1-2), 79-83. https://doi.org/10.1016/j.jns.2015.05.024

Kato, K., Yamazaki, M., Okawa, A., Furuya, T., Sakuma, T., Takahashi, H., . . . Koda, M. (2013). Intravenous administration of granulocyte colony-stimulating factor for treating neuropathic pain associated with compression myelopathy: a phase I and IIa clinical trial. Eur Spine J, 22(1), 197-204. https://doi.org/10.1007/s00586-012-2556-9

Kiguchi, N., Kobayashi, Y., & Kishioka, S. (2012). Chemokines and cytokines in neuroinflammation leading to neuropathic pain. Curr Opin Pharmacol, 12(1), 55-61. https://doi.org/10.1016/j.coph.2011.10.007

Koda, M., Furuya, T., Kato, K., Mannoji, C., Hashimoto, M., Inada, T., . . . Yamazaki, M. (2014). Delayed granulocyte colony-stimulating factor treatment in rats attenuates mechanical allodynia induced by chronic constriction injury of the sciatic nerve. Spine (Phila Pa 1976), 39(3), 192-197. https://doi.org/10.1097/BRS.0000000000000108

Kosacka, J., Nowicki, M., Bluher, M., Baum, P., Stockinger, M., Toyka, K. V., . . . Kloting, N. (2013). Increased autophagy in peripheral nerves may protect Wistar Ottawa Karlsburg W rats against neuropathy. Exp Neurol, 250, 125-135. https://doi.org/10.1016/j.expneurol.2013.09.017

Kress, M., Huttenhofer, A., Landry, M., Kuner, R., Favereaux, A., Greenberg, D., . . . Soreq, H. (2013). microRNAs in nociceptive circuits as predictors of future clinical applications. Front Mol Neurosci, 6, 33. https://doi.org/10.3389/fnmol.2013.00033

Kynast, K. L., Russe, O. Q., Moser, C. V., Geisslinger, G., & Niederberger, E. (2013). Modulation of central nervous system-specific microRNA-124a alters the inflammatory response in the formalin test in mice. Pain, 154(3), 368-376. https://doi.org/10.1016/j.pain.2012.11.010

Lee, K. M., Jeon, S. M., & Cho, H. J. (2010). Interleukin-6 induces microglial CX3CR1 expression in the spinal cord after peripheral nerve injury through the activation of p38 MAPK. Eur J Pain, 14(7), 682 e681-612. https://doi.org/10.1016/j.ejpain.2009.10.017

Leveque-El Mouttie, L., Vu, T., Lineburg, K. E., Kuns, R. D., Bagger, F. O., Teal, B. E., . . . Lane, S. W. (2015). Autophagy is required for stem cell mobilization by G-CSF. Blood, 125(19), 2933-2936. https://doi.org/10.1182/blood-2014-03-562660

Li, H., Shen, L., Ma, C., & Huang, Y. (2013). Differential expression of miRNAs in the nervous system of a rat model of bilateral sciatic nerve chronic constriction injury. Int J Mol Med, 32(1), 219-226. https://doi.org/10.3892/ijmm.2013.1381

Li, J. L., Ding, Y. Q., Li, Y. Q., Li, J. S., Nomura, S., Kaneko, T., & Mizuno, N. (1998). Immunocytochemical localization of mu-opioid receptor in primary afferent neurons containing substance P or calcitonin gene-related peptide. A light and electron microscope study in the rat. Brain Res, 794(2), 347-352. http://www.ncbi.nlm.nih.gov/pubmed/9622672

Liao, M. F., Hsu, J. L., Lu, K. T., Chao, P. K., Cheng, M. Y., Hsu, H. C., . . . Ro, L. S. (2020). Granulocyte Colony Stimulating Factor (GCSF) Can Attenuate Neuropathic Pain by Suppressing Monocyte Chemoattractant Protein-1 (MCP-1) Expression, through Upregulating the Early MicroRNA-122 Expression in the Dorsal Root Ganglia. Cells, 9(7). https://doi.org/10.3390/cells9071669

Liao, M. F., Lu, K. T., Hsu, J. L., Lee, C. H., Cheng, M. Y., & Ro, L. S. (2022). The Role of Autophagy and Apoptosis in Neuropathic Pain Formation. Int J Mol Sci, 23(5). https://doi.org/10.3390/ijms23052685

Liao, M. F., Yeh, S. R., Lo, A. L., Chao, P. K., Lee, Y. L., Hung, Y. H., . . . Ro, L. S. (2016). An early granulocyte colony-stimulating factor treatment attenuates neuropathic pain through activation of mu opioid receptors on the injured nerve. Sci Rep, 6, 25490. https://doi.org/10.1038/srep25490

Liao, M. F., Yeh, S. R., Lu, K. T., Hsu, J. L., Chao, P. K., Hsu, H. C., . . . Ro, L. S. (2021). Interactions between Autophagy, Proinflammatory Cytokines, and Apoptosis in Neuropathic Pain: Granulocyte Colony Stimulating Factor as a Multipotent Therapy in Rats with Chronic Constriction Injury. Biomedicines, 9(5). https://doi.org/10.3390/biomedicines9050542

Liu da, Z., Jickling, G. C., Ander, B. P., Hull, H., Zhan, X., Cox, C., . . . Sharp, F. R. (2016). Elevating microRNA-122 in blood improves outcomes after temporary middle cerebral artery occlusion in rats. J Cereb Blood Flow Metab, 36(8), 1374-1383. https://doi.org/10.1177/0271678X15610786

Liu, X., Zhu, M., Ju, Y., Li, A., & Sun, X. (2019). Autophagy dysfunction in neuropathic pain. Neuropeptides, 75, 41-48. https://doi.org/10.1016/j.npep.2019.03.005

Liu, Y. D., Wang, Z. B., Han, G., Jin, L., & Zhao, P. (2019). Hyperbaric oxygen relieves neuropathic pain through AKT/TSC2/mTOR pathway activity to induce autophagy. J Pain Res, 12, 443-451. https://doi.org/10.2147/JPR.S189353

Lopez-Gonzalez, M. J., Landry, M., & Favereaux, A. (2017). MicroRNA and chronic pain: From mechanisms to therapeutic potential. Pharmacol Ther, 180, 1-15. https://doi.org/10.1016/j.pharmthera.2017.06.001

Ma, Z., Han, Q., Wang, X., Ai, Z., & Zheng, Y. (2016). Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury. PLoS One, 11(2), e0148792. https://doi.org/10.1371/journal.pone.0148792

Maiuri, M. C., Zalckvar, E., Kimchi, A., & Kroemer, G. (2007). Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol, 8(9), 741-752. https://doi.org/10.1038/nrm2239

Marinelli, S., Nazio, F., Tinari, A., Ciarlo, L., D'Amelio, M., Pieroni, L., . . . Pavone, F. (2014). Schwann cell autophagy counteracts the onset and chronification of neuropathic pain. Pain, 155(1), 93-107. https://doi.org/10.1016/j.pain.2013.09.013

Menzie-Suderam, J. M., Modi, J., Xu, H., Bent, A., Trujillo, P., Medley, K., . . . Wu, J. Y. (2020). Granulocyte-colony stimulating factor gene therapy as a novel therapeutics for stroke in a mouse model. J Biomed Sci, 27(1), 99. https://doi.org/10.1186/s12929-020-00692-5

Miller, R. J., Jung, H., Bhangoo, S. K., & White, F. A. (2009). Cytokine and chemokine regulation of sensory neuron function. Handb Exp Pharmacol(194), 417-449. https://doi.org/10.1007/978-3-540-79090-7_12

Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008). Autophagy fights disease through cellular self-digestion. Nature, 451(7182), 1069-1075. https://doi.org/10.1038/nature06639

Modi, J., Menzie-Suderam, J., Xu, H., Trujillo, P., Medley, K., Marshall, M. L., . . . Wu, J. Y. (2020). Mode of action of granulocyte-colony stimulating factor (G-CSF) as a novel therapy for stroke in a mouse model. J Biomed Sci, 27(1), 19. https://doi.org/10.1186/s12929-019-0597-7

Moises, H. C., Rusin, K. I., & Macdonald, R. L. (1994). Mu- and kappa-opioid receptors selectively reduce the same transient components of high-threshold calcium current in rat dorsal root ganglion sensory neurons. J Neurosci, 14(10), 5903-5916. http://www.ncbi.nlm.nih.gov/pubmed/7931552

Morstyn, G., Campbell, L., Souza, L. M., Alton, N. K., Keech, J., Green, M., . . . Fox, R. (1988). Effect of granulocyte colony stimulating factor on neutropenia induced by cytotoxic chemotherapy. Lancet, 1(8587), 667-672. http://www.ncbi.nlm.nih.gov/pubmed/2895212

Nakamura, M., Kanda, T., Sasaki, R., Haga, Y., Jiang, X., Wu, S., . . . Yokosuka, O. (2015). MicroRNA-122 Inhibits the Production of Inflammatory Cytokines by Targeting the PKR Activator PACT in Human Hepatic Stellate Cells. PLoS One, 10(12), e0144295. https://doi.org/10.1371/journal.pone.0144295

Netea-Maier, R. T., Plantinga, T. S., van de Veerdonk, F. L., Smit, J. W., & Netea, M. G. (2016). Modulation of inflammation by autophagy: Consequences for human disease. Autophagy, 12(2), 245-260. https://doi.org/10.1080/15548627.2015.1071759

Ni, J., Gao, Y., Gong, S., Guo, S., Hisamitsu, T., & Jiang, X. (2013). Regulation of mu-opioid type 1 receptors by microRNA134 in dorsal root ganglion neurons following peripheral inflammation. Eur J Pain, 17(3), 313-323. https://doi.org/10.1002/j.1532-2149.2012.00197.x

Niederberger, E., Kynast, K., Lotsch, J., & Geisslinger, G. (2011). MicroRNAs as new players in the pain game. Pain, 152(7), 1455-1458. https://doi.org/10.1016/j.pain.2011.01.042

Olianas, M. C., Dedoni, S., & Onali, P. (2012). Potentiation of dopamine D1-like receptor signaling by concomitant activation of delta- and mu-opioid receptors in mouse medial prefrontal cortex. Neurochem Int, 61(8), 1404-1416. https://doi.org/10.1016/j.neuint.2012.10.005

Pajkrt, D., Manten, A., van der Poll, T., Tiel-van Buul, M. M., Jansen, J., Wouter ten Cate, J., & van Deventer, S. J. (1997). Modulation of cytokine release and neutrophil function by granulocyte colony-stimulating factor during endotoxemia in humans. Blood, 90(4), 1415-1424. http://www.ncbi.nlm.nih.gov/pubmed/9269759

Piao, Y., Gwon, D. H., Kang, D. W., Hwang, T. W., Shin, N., Kwon, H. H., . . . Kim, D. W. (2018). TLR4-mediated autophagic impairment contributes to neuropathic pain in chronic constriction injury mice. Mol Brain, 11(1), 11. https://doi.org/10.1186/s13041-018-0354-y

Pollmacher, T., Korth, C., Mullington, J., Schreiber, W., Sauer, J., Vedder, H., . . . Holsboer, F. (1996). Effects of granulocyte colony-stimulating factor on plasma cytokine and cytokine receptor levels and on the in vivo host response to endotoxin in healthy men. Blood, 87(3), 900-905. http://www.ncbi.nlm.nih.gov/pubmed/8562960

Qian, M., Fang, X., & Wang, X. (2017). Autophagy and inflammation. Clin Transl Med, 6(1), 24. https://doi.org/10.1186/s40169-017-0154-5

Qin, L., Wang, Z., Tao, L., & Wang, Y. (2010). ER stress negatively regulates AKT/TSC/mTOR pathway to enhance autophagy. Autophagy, 6(2), 239-247. https://www.ncbi.nlm.nih.gov/pubmed/20104019

Rausch, O., & Marshall, C. J. (1999). Cooperation of p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways during granulocyte colony-stimulating factor-induced hemopoietic cell proliferation. J Biol Chem, 274(7), 4096-4105. http://www.ncbi.nlm.nih.gov/pubmed/9933603

Ren, K., & Dubner, R. (2010). Interactions between the immune and nervous systems in pain. Nat Med, 16(11), 1267-1276. https://doi.org/10.1038/nm.2234

Robertson, J., Beaulieu, J. M., Doroudchi, M. M., Durham, H. D., Julien, J. P., & Mushynski, W. E. (2001). Apoptotic death of neurons exhibiting peripherin aggregates is mediated by the proinflammatory cytokine tumor necrosis factor-alpha. J Cell Biol, 155(2), 217-226. https://doi.org/10.1083/jcb.200107058

Rubinstein, A. D., & Kimchi, A. (2012). Life in the balance - a mechanistic view of the crosstalk between autophagy and apoptosis. J Cell Sci, 125(Pt 22), 5259-5268. https://doi.org/10.1242/jcs.115865

Sakai, A., Saitow, F., Maruyama, M., Miyake, N., Miyake, K., Shimada, T., . . . Suzuki, H. (2017). MicroRNA cluster miR-17-92 regulates multiple functionally related voltage-gated potassium channels in chronic neuropathic pain. Nat Commun, 8, 16079. https://doi.org/10.1038/ncomms16079

Sakai, A., & Suzuki, H. (2013). Nerve injury-induced upregulation of miR-21 in the primary sensory neurons contributes to neuropathic pain in rats. Biochem Biophys Res Commun, 435(2), 176-181. https://doi.org/10.1016/j.bbrc.2013.04.089

Schaeffer, V., Meyer, L., Patte-Mensah, C., Eckert, A., & Mensah-Nyagan, A. G. (2010). Sciatic nerve injury induces apoptosis of dorsal root ganglion satellite glial cells and selectively modifies neurosteroidogenesis in sensory neurons. Glia, 58(2), 169-180. https://doi.org/10.1002/glia.20910

Scheubel, R. J., Bartling, B., Simm, A., Silber, R. E., Drogaris, K., Darmer, D., & Holtz, J. (2002). Apoptotic pathway activation from mitochondria and death receptors without caspase-3 cleavage in failing human myocardium: fragile balance of myocyte survival? J Am Coll Cardiol, 39(3), 481-488. https://doi.org/10.1016/s0735-1097(01)01769-7

Schmidt, Y., Gaveriaux-Ruff, C., & Machelska, H. (2013). mu-Opioid receptor antibody reveals tissue-dependent specific staining and increased neuronal mu-receptor immunoreactivity at the injured nerve trunk in mice. PLoS One, 8(11), e79099. https://doi.org/10.1371/journal.pone.0079099

Scholz, J., Broom, D. C., Youn, D. H., Mills, C. D., Kohno, T., Suter, M. R., . . . Woolf, C. J. (2005). Blocking caspase activity prevents transsynaptic neuronal apoptosis and the loss of inhibition in lamina II of the dorsal horn after peripheral nerve injury. J Neurosci, 25(32), 7317-7323. https://doi.org/10.1523/JNEUROSCI.1526-05.2005

Sekiguchi, M., Sekiguchi, Y., Konno, S., Kobayashi, H., Homma, Y., & Kikuchi, S. (2009). Comparison of neuropathic pain and neuronal apoptosis following nerve root or spinal nerve compression. Eur Spine J, 18(12), 1978-1985. https://doi.org/10.1007/s00586-009-1064-z

Shi, D. N., Yuan, Y. T., Ye, D., Kang, L. M., Wen, J., & Chen, H. P. (2018). MiR-183-5p Alleviates Chronic Constriction Injury-Induced Neuropathic Pain Through Inhibition of TREK-1. Neurochem Res, 43(6), 1143-1149. https://doi.org/10.1007/s11064-018-2529-4

Shi, G., Shi, J., Liu, K., Liu, N., Wang, Y., Fu, Z., . . . Yuan, W. (2013). Increased miR-195 aggravates neuropathic pain by inhibiting autophagy following peripheral nerve injury. Glia, 61(4), 504-512. https://doi.org/10.1002/glia.22451

Shin, J. H., Lim, Y. H., Song, Y. S., So, B. I., Park, J. Y., Fang, C. H., . . . Kim, K. S. (2014). Granulocyte-colony stimulating factor reduces cardiomyocyte apoptosis and ameliorates diastolic dysfunction in Otsuka Long-Evans Tokushima Fatty rats. Cardiovasc Drugs Ther, 28(3), 211-220. https://doi.org/10.1007/s10557-014-6519-8

Siniscalco, D., Fuccio, C., Giordano, C., Ferraraccio, F., Palazzo, E., Luongo, L., . . . de Novellis, V. (2007). Role of reactive oxygen species and spinal cord apoptotic genes in the development of neuropathic pain. Pharmacol Res, 55(2), 158-166. https://doi.org/10.1016/j.phrs.2006.11.009

Solaroglu, I., Cahill, J., Jadhav, V., & Zhang, J. H. (2006). A novel neuroprotectant granulocyte-colony stimulating factor. Stroke, 37(4), 1123-1128. https://doi.org/10.1161/01.STR.0000208205.26253.96

Song, X. S., Cao, J. L., Xu, Y. B., He, J. H., Zhang, L. C., & Zeng, Y. M. (2005). Activation of ERK/CREB pathway in spinal cord contributes to chronic constrictive injury-induced neuropathic pain in rats. Acta Pharmacol Sin, 26(7), 789-798. https://doi.org/10.1111/j.1745-7254.2005.00123.x

Srinivasan, S., Stevens, M., & Wiley, J. W. (2000). Diabetic peripheral neuropathy: evidence for apoptosis and associated mitochondrial dysfunction. Diabetes, 49(11), 1932-1938. https://www.ncbi.nlm.nih.gov/pubmed/11078462

Starobova, H., Nadar, E. I., & Vetter, I. (2020). The NLRP3 Inflammasome: Role and Therapeutic Potential in Pain Treatment. Front Physiol, 11, 1016. https://doi.org/10.3389/fphys.2020.01016

Stein, C., & Lang, L. J. (2009). Peripheral mechanisms of opioid analgesia. Curr Opin Pharmacol, 9(1), 3-8. https://doi.org/10.1016/j.coph.2008.12.009

Stein, C., Schafer, M., & Machelska, H. (2003). Attacking pain at its source: new perspectives on opioids. Nat Med, 9(8), 1003-1008. https://doi.org/10.1038/nm908

Sun, J. H., Yang, B., Donnelly, D. F., Ma, C., & LaMotte, R. H. (2006). MCP-1 enhances excitability of nociceptive neurons in chronically compressed dorsal root ganglia. J Neurophysiol, 96(5), 2189-2199. https://doi.org/10.1152/jn.00222.2006

Sun, W., Zhang, L., & Li, R. (2017). Overexpression of miR-206 ameliorates chronic constriction injury-induced neuropathic pain in rats via the MEK/ERK pathway by targeting brain-derived neurotrophic factor. Neurosci Lett, 646, 68-74. https://doi.org/10.1016/j.neulet.2016.12.047

Taylor, R. C., Cullen, S. P., & Martin, S. J. (2008). Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol, 9(3), 231-241. https://doi.org/10.1038/nrm2312

Thacker, M. A., Clark, A. K., Bishop, T., Grist, J., Yip, P. K., Moon, L. D., . . . McMahon, S. B. (2009). CCL2 is a key mediator of microglia activation in neuropathic pain states. Eur J Pain, 13(3), 263-272. https://doi.org/10.1016/j.ejpain.2008.04.017

Truong, W., Cheng, C., Xu, Q. G., Li, X. Q., & Zochodne, D. W. (2003). Mu opioid receptors and analgesia at the site of a peripheral nerve injury. Ann Neurol, 53(3), 366-375. https://doi.org/10.1002/ana.10465

Tsuda, M., Mizokoshi, A., Shigemoto-Mogami, Y., Koizumi, S., & Inoue, K. (2004). Activation of p38 mitogen-activated protein kinase in spinal hyperactive microglia contributes to pain hypersensitivity following peripheral nerve injury. Glia, 45(1), 89-95. https://doi.org/10.1002/glia.10308

van Raam, B. J., Drewniak, A., Groenewold, V., van den Berg, T. K., & Kuijpers, T. W. (2008). Granulocyte colony-stimulating factor delays neutrophil apoptosis by inhibition of calpains upstream of caspase-3. Blood, 112(5), 2046-2054. https://doi.org/10.1182/blood-2008-04-149575

Vliegenthart, A. D. B., Berends, C., Potter, C. M. J., Kersaudy-Kerhoas, M., & Dear, J. W. (2017). MicroRNA-122 can be measured in capillary blood which facilitates point-of-care testing for drug-induced liver injury. Br J Clin Pharmacol, 83(9), 2027-2033. https://doi.org/10.1111/bcp.13282

Wan, J., Ma, J., Anand, V., Ramakrishnan, S., & Roy, S. (2015). Morphine potentiates LPS-induced autophagy initiation but inhibits autophagosomal maturation through distinct TLR4-dependent and independent pathways. Acta Physiol (Oxf), 214(2), 189-199. https://doi.org/10.1111/apha.12506

Wang, Z., Liu, F., Wei, M., Qiu, Y., Ma, C., Shen, L., & Huang, Y. (2018). Chronic constriction injury-induced microRNA-146a-5p alleviates neuropathic pain through suppression of IRAK1/TRAF6 signaling pathway. J Neuroinflammation, 15(1), 179. https://doi.org/10.1186/s12974-018-1215-4

Wen, Y. R., Suter, M. R., Ji, R. R., Yeh, G. C., Wu, Y. S., Wang, K. C., . . . Wang, C. C. (2009). Activation of p38 mitogen-activated protein kinase in spinal microglia contributes to incision-induced mechanical allodynia. Anesthesiology, 110(1), 155-165. https://doi.org/10.1097/ALN.0b013e318190bc16

Weng, W., Yao, C., Poonit, K., Zhou, X., Sun, C., Zhang, F., & Yan, H. (2019). Metformin relieves neuropathic pain after spinal nerve ligation via autophagy flux stimulation. J Cell Mol Med, 23(2), 1313-1324. https://doi.org/10.1111/jcmm.14033

White, K., Dempsie, Y., Caruso, P., Wallace, E., McDonald, R. A., Stevens, H., . . . Baker, A. H. (2014). Endothelial apoptosis in pulmonary hypertension is controlled by a microRNA/programmed cell death 4/caspase-3 axis. Hypertension, 64(1), 185-194. https://doi.org/10.1161/HYPERTENSIONAHA.113.03037

Wiberg, R., Novikova, L. N., & Kingham, P. J. (2018). Evaluation of apoptotic pathways in dorsal root ganglion neurons following peripheral nerve injury. Neuroreport, 29(9), 779-785. https://doi.org/10.1097/WNR.0000000000001031

Willemen, H. L., Huo, X. J., Mao-Ying, Q. L., Zijlstra, J., Heijnen, C. J., & Kavelaars, A. (2012). MicroRNA-124 as a novel treatment for persistent hyperalgesia. J Neuroinflammation, 9, 143. https://doi.org/10.1186/1742-2094-9-143

Xie, X., Ma, L., Xi, K., Zhang, W., & Fan, D. (2017). MicroRNA-183 Suppresses Neuropathic Pain and Expression of AMPA Receptors by Targeting mTOR/VEGF Signaling Pathway. Cell Physiol Biochem, 41(1), 181-192. https://doi.org/10.1159/000455987

Xu, L., Huang, Y., Yu, X., Yue, J., Yang, N., & Zuo, P. (2007). The influence of p38 mitogen-activated protein kinase inhibitor on synthesis of inflammatory cytokine tumor necrosis factor alpha in spinal cord of rats with chronic constriction injury. Anesth Analg, 105(6), 1838-1844, table of contents. https://doi.org/10.1213/01.ane.0000287660.29297.7b

Yamazaki, M., Sakuma, T., Kato, K., Furuya, T., & Koda, M. (2013). Granulocyte colony-stimulating factor reduced neuropathic pain associated with thoracic compression myelopathy: report of two cases. J Spinal Cord Med, 36(1), 40-43. https://doi.org/10.1179/2045772312Y.0000000023

Yao, X. L., Lu, X. L., Yan, C. Y., Wan, Q. L., Cheng, G. C., & Li, Y. M. (2015). Circulating miR-122-5p as a potential novel biomarker for diagnosis of acute myocardial infarction. Int J Clin Exp Pathol, 8(12), 16014-16019. https://www.ncbi.nlm.nih.gov/pubmed/26884877

Ye, L., Huang, Y., Zhao, L., Li, Y., Sun, L., Zhou, Y., . . . Zheng, J. C. (2013). IL-1beta and TNF-alpha induce neurotoxicity through glutamate production: a potential role for neuronal glutaminase. J Neurochem, 125(6), 897-908. https://doi.org/10.1111/jnc.12263

Yuan, J., & Yankner, B. A. (2000). Apoptosis in the nervous system. Nature, 407(6805), 802-809. https://doi.org/10.1038/35037739

Zavala, F., Abad, S., Ezine, S., Taupin, V., Masson, A., & Bach, J. F. (2002). G-CSF therapy of ongoing experimental allergic encephalomyelitis via chemokine- and cytokine-based immune deviation. J Immunol, 168(4), 2011-2019. https://doi.org/10.4049/jimmunol.168.4.2011

Zhang, E., Yi, M. H., Ko, Y., Kim, H. W., Seo, J. H., Lee, Y. H., . . . Kim, D. W. (2013). Expression of LC3 and Beclin 1 in the spinal dorsal horn following spinal nerve ligation-induced neuropathic pain. Brain Res, 1519, 31-39. https://doi.org/10.1016/j.brainres.2013.04.055

Zhang, H., Boyette-Davis, J. A., Kosturakis, A. K., Li, Y., Yoon, S. Y., Walters, E. T., & Dougherty, P. M. (2013). Induction of monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR2 in primary sensory neurons contributes to paclitaxel-induced peripheral neuropathy. J Pain, 14(10), 1031-1044. https://doi.org/10.1016/j.jpain.2013.03.012

Zhang, J., Zhang, H., & Zi, T. (2015). Overexpression of microRNA-141 relieves chronic constriction injury-induced neuropathic pain via targeting high-mobility group box 1. Int J Mol Med, 36(5), 1433-1439. https://doi.org/10.3892/ijmm.2015.2342

Zhang, Y. Q., Guo, N., Peng, G., Wang, X., Han, M., Raincrow, J., . . . Yu, L. (2009). Role of SIP30 in the development and maintenance of peripheral nerve injury-induced neuropathic pain. Pain, 146(1-2), 130-140. https://doi.org/10.1016/j.pain.2009.07.011

Zhao, L., Zhu, Y., Wang, D., Chen, M., Gao, P., Xiao, W., . . . Chen, Q. (2010). Morphine induces Beclin 1- and ATG5-dependent autophagy in human neuroblastoma SH-SY5Y cells and in the rat hippocampus. Autophagy, 6(3), 386-394. https://www.ncbi.nlm.nih.gov/pubmed/20190558

Zhuang, Z. Y., Gerner, P., Woolf, C. J., & Ji, R. R. (2005). ERK is sequentially activated in neurons, microglia, and astrocytes by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model. Pain, 114(1-2), 149-159. https://doi.org/10.1016/j.pain.2004.12.022