https://doi.org/10.4081/ejh.2021.3184
PDTC ameliorates neuropathic pain by inhibiting microglial activation via blockage of the TNFα-CX3CR1 pathway
Submitted: 30 September 2020
Accepted: 18 January 2021
Published: 12 March 2021
Accepted: 18 January 2021
Abstract Views: 1067
PDF: 658
HTML: 8
HTML: 8
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Previous studies have suggested that pyrrolidine dithiocarbamate (PDTC), a nuclear factor κB (NF-κB) inhibitor, play a role in deterring nerve injury-induced neuropathic pain (NP) The activation of NF-κB pathway may contribute to spinal microglial activation, CX3CR1 and tumor necrosis factor-alpha (TNF-a) up-regulation. The aim of this study was to clarify whether PDTC could inhibit the development of neuropathic pain via decreasing TNF-a-induced CX3CR1 up-regulation. Sprague-Dawley rats were randomly divided into sham group and NP group. Rats in each group were treated with intrathecal infusion of PDTC (100 or 1000 pmol/d) or saline. The sciatic nerve chronic constriction injury (CCI) model was used to induce NP in rats. Mechanical stimuli and radiant heat were used to evaluate mechanical allodynia and thermal hyperalgesia. Spinal microglial marker OX42 and TNF-a were detected by immunohistochemistry. In vitro BV-2 microglia activation was induced by TNF-a incubation, and the levels of CX3CR1 were assessed by Western blot and reverse transcription-polymerase chain reaction. Pain behavior and immunohistochemistry results showed that intrathecal infusion of PDTC at 100 or 1000 pmol/d prevented the development of mechanical and thermal hyperalgesia, spinal microglial activation and TNF-a expression induced by sciatic nerve CCI in rats. In vitro experiment results showed that PDTC inhibited the TNF-a-induced CX3CR1 up-regulation in BV-2 microglial cells. In conclusion, intrathecal infusion of PDTC could attenuate the pain-related behaviors induced by sciatic nerve CCI through suppressing the spinal microglia activation and TNF-a up-regulation in rats. The NF-κB activation might be responsible for TNF-a-induced CX3CR1 up-regulation in microglia.
Liu ZH, Miao GS, Wang JN, Yang CX, Fu ZJ, Sun T, et al. Inhibits mechanical hypersensitivity in sciatica by modulating the expression of nuclear factor-[kappa]B, phospho-extracellular signal–regulated kinase, and pro- and anti-inflammatory cytokines in the spinal cord and dorsal root ganglion. Anesthesiology 2016;124:934-44.
DOI: https://doi.org/10.1097/ALN.0000000000001010
Zhou, YL, Jiang GQ, Wei JR, Zhang HH, Chen W, Zhu HY, et al. Enhanced binding capability of nuclear factor-kappa B with demethylated P2X3 receptor gene contributes to cancer pain in rats. Pain 2015;156:1892-905.
DOI: https://doi.org/10.1097/j.pain.0000000000000248
Qian LP, Shen SR, Chen JJ, Ji LL, Cao S. Peripheral KATP activation inhibits pain sensitization induced by skin/muscle incision and retraction via the nuclear factor-κB/c-Jun N-terminal kinase signaling pathway. Mol Med Rep 2016;14:2632-38.
DOI: https://doi.org/10.3892/mmr.2016.5546
Xu T, Li D, Zhou X, Ouyang HD, Zhou LJ, Zhou H, et al. Oral application of magnesium-L-threonate attenuates vincristine-induced allodynia and hyperalgesia by normalization of tumor necrosis factor-α/nuclear factor-κB. Anesthesiology 2017;126:1151-68.
DOI: https://doi.org/10.1097/ALN.0000000000001601
Zhang Q, Yu J, Wang J, Ding CP, Han SP, Zeng XY, et al. The red nucleus TNF-α paticipates in the initiation and maintenance of neuropathic pain through different signaling pathways. Neurochem Res 2015;40: 360-71.
DOI: https://doi.org/10.1007/s11064-015-1599-9
Nieto FR, Clark AK, Grist J, Chapman V, Malcangio M. Calcitonin gene-related peptide-expressing sensory neurons and spinal microglial reactivity contribute to pain states in collagen-induced arthritis. Arthritis Rheumatol 2015;67:1668-77.
DOI: https://doi.org/10.1002/art.39082
Nieto FR, Clark AK, Grist J, Hathway GJ, Chapman V, Malcangio M. Neuron-immune mechanisms contribute to pain in early stages of arthritis. J Neuroinflammation 2016;13:96.
DOI: https://doi.org/10.1186/s12974-016-0556-0
Li Z, Wei H, Piirainen S, Chen Z, Kalso E, Pertovaara A, et al. Spinal versus brain microglial and macrophage activation traits determine the differential neuroinflammatory responses and analgesic effect of minocycline in chronic neuropathic pain. Brain Behav Immun 2016;58:107-17.
DOI: https://doi.org/10.1016/j.bbi.2016.05.021
Moini-Zanjani T, Ostad SN, Labibi F, Ameli H, Mosaffa N, Sabetkasaei M. Minocycline effects on IL-6 concentration in macrophage and microglial cells in a rat model of neuropathic pain. Iran Biomed J 2016;20:273-9.
Liu Z, Chen S, Qiu C, Sun Y, Li W, Jiang J, et al. Fractalkine/CX3CR1 contributes to endometriosis-induced neuropathic pain and mechanical hypersensitivity in rats. Front Cell Neurosci 2018;12:495.
DOI: https://doi.org/10.3389/fncel.2018.00495
Wang ZC, Li LH, Bian C, Yang L, Lv N, Zhang YQ. Involvement of NF-κB and the CX3CR1 signaling network in mechanical allodynia induced by tetanic sciatic stimulation. Neurosci Bull 2018;34:64-73.
DOI: https://doi.org/10.1007/s12264-017-0149-7
Pan YD, Guo QL, Wang E, Ye Z, He ZH, Zou WY, et al. Intrathecal infusion of pyrrolidine dithiocarbamate for the prevention and reversal of neuropathic pain in rats using a sciatic chronic constriction injury model. Reg Anesth Pain Med 2010;35:231-7.
DOI: https://doi.org/10.1097/AAP.0b013e3181df245b
Wen C, Xu M, Mo C, Cheng Z, Guo Q, Zhu X. JMJD6 exerts function in neuropathic pain by regulating NF‑κB following peripheral nerve injury in rats. Int J Mol Med 2018;42:633-42.
DOI: https://doi.org/10.3892/ijmm.2018.3613
Hou X, Weng Y, Wang T, Ouyang B, Li Y, Song Z, et al. Suppression of HDAC2 in spinal cord alleviates mechanical hyperalgesia and restores KCC2 expression in a rat model of bone cancer pain. Neuroscience 2018;377:138-49.
DOI: https://doi.org/10.1016/j.neuroscience.2018.02.026
Tian G, Luo X, Tang C, Cheng X, Chung SK, Xia Z, et al. Astrocyte contributes to pain development via MMP2-JNK1/2 signaling in a mouse model of complex regional pain syndrome. Life Sci 2017;170:64-71.
DOI: https://doi.org/10.1016/j.lfs.2016.11.030
Ye Z, Li Q, Guo Q, Xiong Y, Guo D, Yang H, et al. Ketamine induces hippocampal apoptosis through a mechanism associated with the caspase-1 dependent pyroptosis. Neuropharmacology 2018;128:63-75.
DOI: https://doi.org/10.1016/j.neuropharm.2017.09.035
Bennett GJ, Xie Yikuan. Peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988;33:87-107.
DOI: https://doi.org/10.1016/0304-3959(88)90209-6
Hao S, Mata M, Glorioso JC, Fink DJ. Gene transfer to interfere with TNFalpha signaling in neuropathic pain. Gene Ther 2007;14:1010-6.
DOI: https://doi.org/10.1038/sj.gt.3302950
Wu Z, Wang S, Wu I, Mata M, Fink DJ. Activation of TLR-4 to produce tumour necrosis factor-α in neuropathic pain caused by paclitaxel. Eur J Pain 2015;19:889-98.
DOI: https://doi.org/10.1002/ejp.613
Yu HM, Wang Q, Sun WB. Silencing of FKBP51 alleviates the mechanical pain threshold, inhibits DRG inflammatory factors and pain mediators through the NF-kappaB signaling pathway. Gene 2017;627:169-75.
DOI: https://doi.org/10.1016/j.gene.2017.06.029
Hartung JE, Eskew O, Wong T, Tchivileva IE, Oladosu FA, O'Buckley SC, et al. Nuclear factor-kappa B regulates pain and COMT expression in a rodent model of inflammation. Brain Behav Immun 2015;50:196-202.
DOI: https://doi.org/10.1016/j.bbi.2015.07.014
Meffert MK, Baltimore D. Physiological functions for brain NF-kappaB. Trends Neurosci 2005;28:37-43.
DOI: https://doi.org/10.1016/j.tins.2004.11.002
Shin MS, You S, Kang Y, Lee N, Yoo SA, Park K, et al. DNA methylation regulates the differential expression of CX3CR1 on human IL-7Rαlow and IL-7Rαhigh effector memory CD8+ T cells with distinct migratory capacities to the fractalkine. J Immunol 2015;195:2861-9.
DOI: https://doi.org/10.4049/jimmunol.1500877
Sun JL, Xiao C, Lu B, Zhang J, Yuan XZ, Chen W, et al. CX3CL1/CX3CR1 regulates nerve injury-induced pain hypersensitivity through the ERK5 signaling pathway. J Neurosci Res 2013;91:545-53.
DOI: https://doi.org/10.1002/jnr.23168
Ijaz T, Wakamiya M, Sun H, Recinos A 3rd, Tilton RG, Brasier AR. Generation and characterization of a novel transgenic mouse harboring conditional nuclear factor-kappa B/RelA knockout alleles. BMC Dev Biol 2016;16:32.
DOI: https://doi.org/10.1186/s12861-016-0135-8
Kim SH, MacIntyre DA, Firmino Da Silva M, Blanks AM, Lee YS, Thornton S, et al. Oxytocin activates NF-κB-mediated inflammatory pathways in human gestational tissues. Mol Cell Endocrinol 2015;403:64-77.
DOI: https://doi.org/10.1016/j.mce.2014.11.008
How to Cite
Li, X. ., Ye, Z. ., Guo, Q. ., Wang, E. ., & Pan, Y. (2021). PDTC ameliorates neuropathic pain by inhibiting microglial activation <em>via</em> blockage of the TNFα-CX3CR1 pathway. European Journal of Histochemistry, 65(1). https://doi.org/10.4081/ejh.2021.3184
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- Liqin Xi, Chen Wang, Pengyu Chen, Qi Yang, Ruiqi Hu, Haolin Zhang, Qiang Weng, Meiyu Xu, Expressions of IL-6, TNF-α and NF-κB in the skin of Chinese brown frog (Rana dybowskii) , European Journal of Histochemistry: Vol. 61 No. 4 (2017)
- F. Rappa, E. Unti, P. Baiamonte, F. Cappello, N. Scibetta, Different immunohistochemical levels of Hsp60 and Hsp70 in a subset of brain tumors and putative role of Hsp60 in neuroepithelial tumorigenesis , European Journal of Histochemistry: Vol. 57 No. 2 (2013)
- Kazuhiko Hashimoto, Shunji Nishimura, Tomohiko Ito, Ryosuke Kakinoki, Masao Akagi, Immunohistochemical expression and clinicopathological assessment of PD-1, PD-L1, NY-ESO-1, and MAGE-A4 expression in highly aggressive soft tissue sarcomas , European Journal of Histochemistry: Vol. 66 No. 2 (2022)
- Zhanshu Ma, Qi Gao, Wenjing Xin, Lei Wang, Yan Chen, Chang Su, Songyan Gao, Ruiling Sun, The role of miR-143-3p/FNDC1 axis on the progression of non-small cell lung cancer , European Journal of Histochemistry: Vol. 67 No. 2 (2023)
- J.M. Ou, Z.Y. Yu, M.K. Qiu, Y.X. Dai, Q. Dong, J. Shen, X.F. Wang, Y.B. Liu, Z.W. Quan, Z.W. Fei, Knockdown of VEGFR2 inhibits proliferation and induces apoptosis in hemangioma-derived endothelial cells , European Journal of Histochemistry: Vol. 58 No. 1 (2014)
- S. Gurzu, M. Krause, I. Ember, L. Azamfirei, G. Gobel, K. Feher, I. Jung, Mena, a new available marker in tumors of salivary glands? , European Journal of Histochemistry: Vol. 56 No. 1 (2012)
- D.G.B. Araújo, L. Nakao, P. Gozzo, C.D.A. Souza, V. Balderrama, E.S. Gugelmin, A.P. Kuczynski, M. Olandoski, L. de Noronha, Expression level of quiescin sulfhydryl oxidase 1 (QSOX1) in neuroblastomas , European Journal of Histochemistry: Vol. 58 No. 1 (2014)
- T. Bujas, Z. Marusic, M. Peric Balja, A. Mijic, B. Kruslin, D. Tomas, MAGE-A3/4 and NY-ESO-1 antigens expression in metastatic esophageal squamous cell carcinoma , European Journal of Histochemistry: Vol. 55 No. 1 (2011)
- Jacopo J.V. Branca, Donatello Carrino, Ferdinando Paternostro, Massimo Gulisano, Matteo Becatti, Lorenzo Di Cesare Mannelli, Alessandra Pacini, Antioxidant support to ameliorate the oxaliplatin-dependent microglial alteration: morphological and molecular study , European Journal of Histochemistry: Vol. 65 No. s1 (2021): Special Collection on Advances in Neuromorphology in Health and Disease
- Y. Zhang, Y.J. Tang, Z.H. Li, F. Pan, K. Huang, G.H. Xu, KiSS1 inhibits growth and invasion of osteosarcoma cells through inhibition of the MAPK pathway , European Journal of Histochemistry: Vol. 57 No. 4 (2013)
<< < 1 2 3 4 5 6 7 8 9 10 > >>
You may also start an advanced similarity search for this article.
