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Molecular Pain
Published in: Molecular Pain 1/2015

Open Access 01-12-2015 | Research

Paclitaxel induces acute pain via directly activating toll like receptor 4

Authors: Xisheng Yan, Dylan W Maixner, Ruchi Yadav, Mei Gao, Pei Li, Michael G Bartlett, Han-Rong Weng

Published in: Molecular Pain | Issue 1/2015

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Abstract

Paclitaxel, a powerful anti-neoplastic drug, often causes pathological pain, which significantly reduces the quality of life in patients. Paclitaxel-induced pain includes pain that occurs immediately after paclitaxel treatment (paclitaxel-associated acute pain syndrome, P-APS) and pain that persists for weeks to years after cessation of paclitaxel treatment (paclitaxel induced chronic neuropathic pain). Mechanisms underlying P-APS remain unknown. In this study, we found that paclitaxel causes acute pain in rodents in a dose-dependent manner. The paclitaxel-induced acute pain occurs within 2 hrs after a single intravenous injection of paclitaxel. This is accompanied by low levels of paclitaxel penetrating into the cerebral spinal fluid and spinal dorsal horn. We demonstrated that an intrathecal injection of paclitaxel induces mechanical allodynia in a dose-dependent manner. Paclitaxel causes activation of toll like receptor 4 (TLR4) in the spinal dorsal horn and dorsal root ganglions. Through activating TLR4, paclitaxel increases glutamatergic synaptic activities and reduces glial glutamate transporter activities in the dorsal horn. Activations of TLR4 are necessary in the genesis of paclitaxel-induced acute pain. The cellular and molecular signaling pathways revealed in this study could provide rationales for the development of analgesics and management strategies for P-APS in patients.
Literature
1.
Reeves BN, Dakhil SR, Sloan JA, Wolf SL, Burger KN, Kamal A, et al. Further data supporting that paclitaxel-associated acute pain syndrome is associated with development of peripheral neuropathy: North Central Cancer Treatment Group trial N08C1. Cancer. 2012;118:5171–8.CrossRefPubMedCentralPubMed
2.
Loprinzi CL, Reeves BN, Dakhil SR, Sloan JA, Wolf SL, Burger KN, et al. Natural history of paclitaxel-associated acute pain syndrome: prospective cohort study NCCTG N08C1. J Clin Oncol. 2011;29:1472–8.CrossRefPubMedCentralPubMed
3.
Cata JP, Weng HR, Dougherty PM. Clinical and experimental findings in humans and animals with chemotherapy-induced peripheral neuropathy. Minerva Anes. 2006;72:151–69.
4.
Dougherty PM, Cata JP, Cordella JV, Burton A, Weng HR. Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients. Pain. 2004;109:132–42.CrossRefPubMed
5.
Rowinsky EK, Eisenhauer EA, Chaudhry V, Arbuck SG, Donehower RC. Clinical toxicities encountered with paclitaxel (Taxol). Semin Oncol. 1993;20:1–15.PubMed
6.
Garrison JA, McCune JS, Livingston RB, Linden HM, Gralow JR, Ellis GK, et al. Myalgias and arthralgias associated with paclitaxel. Oncology (Williston Park). 2003;17:271–7. discussion 281–272, 286–278.
7.
White CM, Martin BK, Lee LF, Haskill JS, Ting JPY. Effects of paclitaxel on cytokine synthesis by unprimed human monocytes, T lymphocytes, and breast cancer cells. Cancer Immunol Immunother. 1998;46:104–12.CrossRefPubMed
8.
Manthey CL, Brandes ME, Perera PY, Vogel SN. Taxol increases steady-state levels of lipopolysaccharide-inducible genes and protein-tyrosine phosphorylation in murine macrophages. J Immunol. 1992;149:2459–65.PubMed
9.
Wang AC, Su QB, Wu FX, Zhang XL, Liu PS. Role of TLR4 for paclitaxel chemotherapy in human epithelial ovarian cancer cells. Eur J Clin Invest. 2009;39:157–64.CrossRefPubMed
10.
Moos PJ, Fitzpatrick FA. Taxane-mediated gene induction is independent of microtubule stabilization: Induction of trancription regulators and enzymes that modulate inflammation and apoptosis. Proc Natl Acad Sci U S A. 1998;95:3896–901.CrossRefPubMedCentralPubMed
11.
Lehnardt S, Lachance C, Patrizi S, Lefebvre S, Follett PL, Jensen FE, et al. The toll-like receptor TLR4 is necessary for lipopolysaccharide-induced oligodendrocyte injury in the CNS. J Neurosci Off J Soc Neurosci. 2002;22:2478–86.
12.
Olson JK, Miller SD. Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J Immunol. 2004;173:3916–24.CrossRefPubMed
13.
Bettoni I, Comelli F, Rossini C, Granucci F, Giagnoni G, Peri F, et al. Glial TLR4 receptor as new target to treat neuropathic pain: efficacy of a new receptor antagonist in a model of peripheral nerve injury in mice. Glia. 2008;56:1312–9.CrossRefPubMed
14.
Tanga FY, Nutile-McMenemy N, DeLeo JA. The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy. Proc Natl Acad Sci U S A. 2005;102:5856–61.CrossRefPubMedCentralPubMed
15.
Wu FX, Bian JJ, Miao XR, Huang SD, Xu XW, Gong DJ, et al. Intrathecal siRNA against Toll-like receptor 4 reduces nociception in a rat model of neuropathic pain. Int J Med Sci. 2010;7:251–9.CrossRefPubMedCentralPubMed
16.
Glantz MJ, Choy H, Kearns CM, Mills PC, Wahlberg LU, Zuhowski EG, et al. Paclitaxel disposition in plasma and central nervous systems of humans and rats with brain tumors. J Natl Cancer Inst. 1995;87:1077–81.CrossRefPubMed
17.
Chen J, Balmaceda C, Bruce JN, Sisti MB, Huang M, Cheung YK, et al. Tamoxifen paradoxically decreases paclitaxel deposition into cerebrospinal fluid of brain tumor patients. J Neurooncol. 2006;76:85–92.CrossRefPubMed
18.
Cavaletti G, Cavalletti E, Oggioni N, Sottani C, Minoia C, D”Incalci M, et al. Distribution of paclitaxel within the nervous system of the rat after repeated intravenous administration. Neurotoxicology. 2000;21:389–93.PubMed
19.
Kemper EM, van Zandbergen AE, Cleypool C, Mos HA, Boogerd W, Beijnen JH, et al. Increased penetration of paclitaxel into the brain by inhibition of P-Glycoprotein. Clin Cancer Res. 2003;9:2849–55.PubMed
20.
Fellner S, Bauer B, Miller DS, Schaffrik M, Fankhanel M, Spruss T, et al. Transport of paclitaxel (Taxol) across the blood–brain barrier in vitro and in vivo. J Clin Invest. 2002;110:1309–18.CrossRefPubMedCentralPubMed
21.
22.
23.
24.
25.
Tanaka K, Watase K, Manabe T, Yamada K, Watanabe M, Takahashi K, et al. Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science. 1997;276:1699–702.CrossRefPubMed
26.
Weng HR, Aravindan N, Cata JP, Chen JH, Shaw AD, Dougherty PM. Spinal glial glutamate transporters downregulate in rats with taxol-induced hyperalgesia. Neurosci Lett. 2005;386:18–22.CrossRefPubMed
27.
Mao J, Sung B, Ji RR, Lim G. Chronic morphine induces downregulation of spinal glutamate transporters: implications in morphine tolerance and abnormal pain sensitivity. J Neurosci. 2002;22:8312–23.PubMed
28.
Doyle T, Chen Z, Muscoli C, Bryant L, Esposito E, Cuzzocrea S, et al. Targeting the overproduction of peroxynitrite for the prevention and reversal of paclitaxel-induced neuropathic pain. J Neurosci Off J Soc Neurosci. 2012;32:6149–60.CrossRef
29.
Nie H, Weng HR. Impaired glial glutamate uptake induces extrasynaptic glutamate spillover in the spinal sensory synapses of neuropathic rats. J Neurophysiol. 2010;103:2570–80.CrossRefPubMedCentralPubMed
30.
Nie H, Zhang H, Weng HR. Minocycline prevents impaired glial glutamate uptake in the spinal sensory synapses of neuropathic rats. Neuroscience. 2010;170:901–12.CrossRefPubMedCentralPubMed
31.
Sung B, Lim G, Mao J. Altered expression and uptake activity of spinal glutamate transporters after nerve injury contribute to the pathogenesis of neuropathic pain in rats. J Neurosci. 2003;23:2899–910.PubMed
32.
Dina OA, Chen X, Reichling D, Levine JD. Role of protein kinase C[epsi] and protein kinase A in a model of paclitaxel-induced painful peripheral neuropathy in the rat. Neuroscience. 2001;108:507–15.CrossRefPubMed
33.
Rutten K, Robens A, Read S, Christoph T. Pharmacological validation of a refined burrowing paradigm for prediction of analgesic efficacy in a rat model of sub‐chronic knee joint inflammation. Eur J Pain. 2014;18:213–22.CrossRefPubMed
34.
Andrews N, Legg E, Lisak D, Issop Y, Richardson D, Harper S, et al. Spontaneous burrowing behaviour in the rat is reduced by peripheral nerve injury or inflammation associated pain. Eur J Pain. 2012;16:485–95.CrossRefPubMed
35.
Ding AH, Porteu F, Sanchez E, Nathan CF. Shared actions of endotoxin and taxol on TNF receptors and TNF release. Science. 2002;248:370–2.CrossRef
36.
Zaks-Zilberman M, Zaks TZ, Vogel SN. Induction of proinflammatory and chemokine genes by lipopolysaccharide and paclitaxel (Taxol) in murine and human breast cancer cell lines. Cytokine+. 2001;15:156–65.PubMed
37.
Chen LY, Zuraw BL, Zhao M, Liu FT, Huang S, Pan ZK. Involvement of protein tyrosine kinase in Toll-like receptor 4-mediated NF-kappa B activation in human peripheral blood monocytes. Am J Physiol Lung Cell Mol Physiol. 2003;284:L607–13.CrossRefPubMed
38.
Medvedev AE, Piao W, Shoenfelt J, Rhee SH, Chen H, Basu S, et al. Role of TLR4 tyrosine phosphorylation in signal transduction and endotoxin tolerance. J Biol Chem. 2007;282:16042–53.CrossRefPubMedCentralPubMed
39.
Christianson CA, Dumlao DS, Stokes JA, Dennis EA, Svensson CI, Corr M, et al. Spinal TLR4 mediates the transition to a persistent mechanical hypersensitivity after the resolution of inflammation in serum-transferred arthritis. Pain. 2011;152:2881–91.CrossRefPubMedCentralPubMed
40.
Li X, Wang XW, Feng XM, Zhou WJ, Wang YQ, Mao-Ying QL. Stage-dependent anti-allodynic effects of intrathecal Toll-like receptor 4 antagonists in a rat model of cancer induced bone pain. J Physiol Sci. 2013;63:203–9.CrossRefPubMed
41.
Lewis SS, Hutchinson MR, Zhang Y, Hund DK, Maier SF, Rice KC, et al. Glucuronic acid and the ethanol metabolite ethyl-glucuronide cause toll-like receptor 4 activation and enhanced pain. Brain Behav Immun. 2013;30:24–32.CrossRefPubMedCentralPubMed
42.
Salter MW, Pitcher GM. Dysregulated Src upregulation of NMDA receptor activity: a common link in chronic pain and schizophrenia. Febs J. 2012;279:2–11.CrossRefPubMedCentralPubMed
43.
Grace PM, Hutchinson MR, Maier SF, Watkins LR. Pathological pain and the neuroimmune interface. Nat Rev Immunol. 2014;14:217–31.CrossRefPubMed
44.
Yan X, Weng HR. Endogenous interleukin-1b in neuropathic rats enhances glutamate release from the primary afferents in the spinal dorsal horn through coupling with presynaptic NMDA receptors. J Biol Chem. 2013;288:30544–57.CrossRefPubMed
45.
Yan X, Jiang E, Gao M, Weng HR. Endogenous activation of presynaptic NMDA receptors enhances glutamate release from the primary afferents in the spinal dorsal horn in a rat model of neuropathic pain. J Physiol. 2013;591:2001–19.CrossRefPubMedCentralPubMed
46.
Lissin DV, Carroll RC, Nicoll RA, Malenka RC, von Zastrow M. Rapid, activation-induced redistribution of ionotropic glutamate receptors in cultured hippocampal neurons. J Neurosci. 1999;19:1263–72.PubMed
47.
Kumazawa T, Perl ER. Primate cutaneous receptors with unmyelinated (C) fibres and their projection to the substantia gelatinosa. J Physiol. 1977;73:287–304.
48.
Nie H, Weng HR. Glutamate transporters prevent excessive activation of NMDA receptors and extrasynaptic glutamate spillover in the spinal dorsal horn. J Neurophysiol. 2009;101:2041–51.CrossRefPubMed
49.
Weng HR, Chen JH, Pan ZZ, Nie H. Glial glutamate transporter 1 regulates the spatial and temporal coding of glutamatergic synaptic transmission in spinal lamina II neurons. Neuroscience. 2007;149:898–907.CrossRefPubMed
50.
Mitrovic AD, Maddison JE, Johnston GA. Influence of the oestrous cycle on L-glutamate and L-aspartate transport in rat brain synaptosomes. Neurochem Int. 1999;34:101–8.CrossRefPubMed
51.
Yan X, Yadav R, Gao M, Weng HR. Interleukin-1 beta enhances endocytosis of glial glutamate transporters in the spinal dorsal horn through activating protein kinase C. Glia. 2014;62(7):1093–109.CrossRefPubMed
52.
Levy LM, Warr O, Attwell D. Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na + −dependent glutamate uptake. J Neurosci. 1998;18:9620–8.PubMed
53.
Wadiche JI, Arriza JL, Amara SG, Kavanaugh MP. Kinetics of a human glutamate transporter. Neuron. 1995;14:1019–27.CrossRefPubMed
54.
Tegeder I, Adolph J, Schmidt H, Woolf CJ, Geisslinger G, Lotsch J. Reduced hyperalgesia in homozygous carriers of a GTP cyclohydrolase 1 haplotype. Eur J Pain. 2008;12:1069–77.CrossRefPubMed
55.
Adolph O, Koster S, Rath M, Georgieff M, Weigt HU, Engele J, et al. Rapid increase of glial glutamate uptake via blockade of the protein kinase A pathway. Glia. 2007;55:1699–707.CrossRefPubMed
56.
Bergles DE, Jahr CE. Synaptic activation of glutamate transporters in hippocampal astrocytes. Neuron. 1997;19:1297–308.CrossRefPubMed
57.
Fang H, Huang Y, Zuo Z. The different responses of rat glutamate transporter type 2 and its mutant (tyrosine 403 to histidine) activity to volatile anesthetics and activation of protein kinase C. Brain Res. 2002;953:255–64.CrossRefPubMed
58.
Chen N, Sugihara H, Sharma J, Perea G, Petravicz J, Le C, et al. Nucleus basalis-enabled stimulus-specific plasticity in the visual cortex is mediated by astrocytes. Proc Natl Acad Sci U S A. 2012;109:E2832–41.CrossRefPubMedCentralPubMed
59.
Schwendele B, Brawek B, Hermes M, Garaschuk O. High-resolution in vivo imaging of microglia using a versatile nongenetically encoded marker. Eur J Immunol. 2012;42:2193–6.CrossRefPubMed
60.
Shimamoto K, Sakai R, Takaoka K, Yumoto N, Nakajima T, Amara SG, et al. Characterization of novel L-threo-beta-benzyloxyaspartate derivatives, potent blockers of the glutamate transporters. Mol Pharmacol. 2004;65:1008–15.CrossRefPubMed
61.
Gouma E, Simos Y, Verginadis I, Lykoudis E, Evangelou A, Karkabounas S. A simple procedure for estimation of total body surface area and determination of a new value of Meeh’s constant in rats. Lab Anim. 2012;46:40–5.CrossRefPubMed
62.
Gilpin DA. Calculation of a new Meeh constant and experimental determination of burn size. Burns. 1996;22:607–11.CrossRefPubMed
63.
Choi SS, Koh WU, Nam JS, Shin JW, Leem JG, Suh JH. Effect of ethyl pyruvate on Paclitaxel-induced neuropathic pain in rats. Korean J Pain. 2013;26:135–41.CrossRefPubMedCentralPubMed
64.
Deng L, Guindon J, Vemuri VK, Thakur GA, White FA, Makriyannis A, et al. The maintenance of cisplatin- and paclitaxel-induced mechanical and cold allodynia is suppressed by cannabinoid CB(2) receptor activation and independent of CXCR4 signaling in models of chemotherapy-induced peripheral neuropathy. Mol Pain. 2012;8:71.CrossRefPubMedCentralPubMed
65.
Polomano RC, Mannes AJ, Clark US, Bennett GJ. A painful peripheral neuropathy in the rat produced by the chemotherapeutic drug, paclitaxel. Pain. 2001;94:293–304.CrossRefPubMed
66.
Tatsushima Y, Egashira N, Kawashiri T, Mihara Y, Yano T, Mishima K, et al. Involvement of substance P in peripheral neuropathy induced by paclitaxel but not oxaliplatin. J Pharmacol Exp Ther. 2011;337:226–35.CrossRefPubMed
67.
Peters CM, Jimenez-Andrade JM, Jonas BM, Sevcik MA, Koewler NJ, Ghilardi JR, et al. Intravenous paclitaxel administration in the rat induces a peripheral sensory neuropathy characterized by macrophage infiltration and injury to sensory neurons and their supporting cells. Exp Neurol. 2007;203:42–54.CrossRefPubMed
68.
Rushing DA. Phase I/II study of weekly irinotecan and paclitaxel in patients with SCLC. Oncology (Williston Park). 2000;14:63–6.
69.
Lokich J, Anderson N, Moore C, Bern M, Coco F, Sonneborn H, et al. Paclitaxel, cisplatin and etoposide combination chemotherapy: a comparison of dose intensity in two multifractionated dose schemas. Eur J Cancer. 1998;34:664–7.CrossRefPubMed
70.
Vahdat LT, Papadopoulos K, Balmaceda C, McGovern T, Dunleavy J, Kaufman E, et al. Phase I trial of sequential high-dose chemotherapy with escalating dose paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer. Clin Cancer Res. 1998;4:1689–95.PubMed
71.
Gluck S, Germond C, Lopez P, Cano P, Dorreen M, Koski T, et al. A phase I trial of high-dose paclitaxel, cyclophosphamide and mitoxantrone with autologous blood stem cell support for the treatment of metastatic breast cancer. Eur J Cancer. 1998;34:1008–14.CrossRefPubMed
72.
Somlo G, Doroshow JH, Synold T, Longmate J, Reardon D, Chow W, et al. High-dose paclitaxel in combination with doxorubicin, cyclophosphamide and peripheral blood progenitor cell rescue in patients with high-risk primary and responding metastatic breast carcinoma: toxicity profile, relationship to paclitaxel pharmacokinetics and short-term outcome. Br J Cancer. 2001;84:1591–8.CrossRefPubMedCentralPubMed
73.
Anderson CM, Swanson RA. Astrocyte glutamate transport: review of properties, regulation, and physiological functions. Glia. 2000;32:1–14.CrossRefPubMed
74.
Clements JD. Transmitter timecourse in the synaptic cleft: its role in central synaptic function. Trends Neurosci. 1996;19:163–71.CrossRefPubMed
75.
Sorge RE, LaCroix-Fralish ML, Tuttle AH, Sotocinal SG, Austin JS, Ritchie J, et al. Spinal cord Toll-like receptor 4 mediates inflammatory and neuropathic hypersensitivity in male but not female mice. J Neurosci Off J Soc Neurosci. 2011;31:15450–4.CrossRef
76.
Saito O, Svensson CI, Buczynski MW, Wegner K, Hua XY, Codeluppi S, et al. Spinal glial TLR4-mediated nociception and production of prostaglandin E(2) and TNF. Br J Pharmacol. 2010;160:1754–64.CrossRefPubMedCentralPubMed
77.
Yoon SY, Patel D, Dougherty PM. Minocycline blocks lipopolysaccharide induced hyperalgesia by suppression of microglia but not astrocytes. Neuroscience. 2012;221:214–24.CrossRefPubMedCentralPubMed
78.
Yaksh TL, Rudy TA. Analgesia mediated by a direct spinal action of narcotics. Science. 1976;192:1357–8.CrossRefPubMed
79.
Hylden JL, Wilcox GL. Intrathecal morphine in mice: a new technique. Eur J Pharmacol. 1980;67:313–6.CrossRefPubMed
80.
Xu JJ, Walla BC, Diaz MF, Fuller GN, Gutstein HB. Intermittent lumbar puncture in rats: a novel method for the experimental study of opioid tolerance. Anesth Analg. 2006;103:714–20.CrossRefPubMed
81.
Weng HR, Chen JH, Cata JP. Inhibition of glutamate uptake in the spinal cord induces hyperalgesia and increased responses of spinal dorsal horn neurons to peripheral afferent stimulation. Neuroscience. 2006;138:1351–60.CrossRefPubMed
82.
Weng HR, Cordella JV, Dougherty PM. Changes in sensory processing in the spinal dorsal horn accompany vincristine-induced hyperalgesia and allodynia. Pain. 2003;103:131–8.CrossRefPubMed
83.
Li P, Albrecht BJ, Yan X, Gao M, Weng HR, Bartlett MG. A rapid analytical method for the quantification of paclitaxel in rat plasma and brain tissue by high-performance liquid chromatography and tandem mass spectrometry. Rapid Commun Mass Spectrom. 2013;27:2127–34.CrossRefPubMed
84.
Nakatsuka T, Tsuzuki K, Ling JX, Sonobe H, Gu JG. Distinct roles of P2X receptors in modulatiing glutamate release at different primary sensory synapses in rat spinal cord. J Neurophysiol. 2003;89:3243–52.CrossRefPubMed
85.
Yoshimura M, Jessell TM. Primary afferent-evoked synaptic responses and slow potential generation in rat substantia gelatinosa neurons in vitro. J Neurophysiol. 1989;62:96–108.PubMed
86.
87.
Devaraju P, Sun MY, Myers TL, Lauderdale K, Fiacco TA. Astrocytic group I mGluR-dependent potentiation of astrocytic glutamate and potassium uptake. J Neurophysiol. 2013;109:2404–14.CrossRefPubMed
88.
Sung B, Wang S, Zhou B, Lim G, Yang L, Zeng Q, et al. Altered spinal arachidonic acid turnover after peripheral nerve injury regulates regional glutamate concentration and neuropathic pain behaviors in rats. Pain. 2007;131:121–31.CrossRefPubMedCentralPubMed
89.
Azbill RD, Mu X, Springer JE. Riluzole increases high-affinity glutamate uptake in rat spinal cord synaptosomes. Brain Res. 2000;871:175–80.CrossRefPubMed
90.
Matthias K, Kirchhoff F, Seifert G, Huttmann K, Matyash M, Kettenmann H, et al. Segregated expression of AMPA-type glutamate receptors and glutamate transporters defines distinct astrocyte populations in the mouse hippocampus. J Neurosci Off J Soc Neurosci. 2003;23:1750–8.
91.
Park CK, Lu N, Xu ZZ, Liu T, Serhan CN, Ji RR. Resolving TRPV1- and TNF-alpha-mediated spinal cord synaptic plasticity and inflammatory pain with neuroprotectin D1. J Neurosci Off J Soc Neurosci. 2011;31:15072–85.CrossRef
Metadata
Title
Paclitaxel induces acute pain via directly activating toll like receptor 4
Authors
Xisheng Yan
Dylan W Maixner
Ruchi Yadav
Mei Gao
Pei Li
Michael G Bartlett
Han-Rong Weng
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Molecular Pain / Issue 1/2015
Electronic ISSN: 1744-8069
DOI
https://doi.org/10.1186/s12990-015-0005-6

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