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Upregulation of ERK phosphorylation in rat dorsal root ganglion neurons contributes to oxaliplatin-induced chronic neuropathic pain


Autoři: Toyoaki Maruta aff001;  Takayuki Nemoto aff002;  Koutaro Hidaka aff001;  Tomohiro Koshida aff001;  Tetsuro Shirasaka aff001;  Toshihiko Yanagita aff003;  Ryu Takeya aff004;  Isao Tsuneyoshi aff001
Působiště autorů: Department of Anesthesiology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan aff001;  Department of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan aff002;  Department of Clinical Pharmacology, School of Nursing, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan aff003;  Department of Pharmacology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan aff004
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0225586

Souhrn

Oxaliplatin is the first-line chemotherapy for metastatic colorectal cancer. Unlike other platinum anticancer agents, oxaliplatin does not result in significant renal impairment and ototoxicity. Oxaliplatin, however, has been associated with acute and chronic peripheral neuropathies. Despite the awareness of these side-effects, the underlying mechanisms are yet to be clearly established. Therefore, in this study, we aimed to understand the factors involved in the generation of chronic neuropathy elicited by oxaliplatin treatment. We established a rat model of oxaliplatin-induced neuropathic pain (4 mg kg-1 intraperitoneally). The paw withdrawal thresholds were assessed at different time-points after the treatment, and a significant decrease was observed 3 and 4 weeks after oxaliplatin treatment as compared to the vehicle treatment (4.4 ± 1.0 vs. 16.0 ± 4.1 g; P < 0.05 and 4.4 ± 0.7 vs. 14.8 ± 3.1 g; P < 0.05, respectively). We further evaluated the role of different mitogen-activated protein kinases (MAPKs) pathways in the pathophysiology of neuropathic pain. Although the levels of total extracellular signal-regulated kinase (ERK) 1/2 in the dorsal root ganglia (DRG) were not different between oxaliplatin and vehicle treatment groups, phosphorylated ERK (p-ERK) 1/2 was up-regulated up to 4.5-fold in the oxaliplatin group. Administration of ERK inhibitor PD98059 (6 μg day-1 intrathecally) inhibited oxaliplatin-induced ERK phosphorylation and neuropathic pain. Therefore, upregulation of p-ERK by oxaliplatin in rat DRG and inhibition of mechanical allodynia by an ERK inhibitor in the present study may provide a better understanding of intracellular molecular alterations associated with oxaliplatin-induced neuropathic pain and help in the development of potential therapeutics.

Klíčová slova:

Allodynia – Apoptosis – Neurons – Neuropathic pain – Neuropathy – Peripheral neuropathy – Phosphorylation – Platinum


Zdroje

1. Extra JM, Marty M, Brienza S, Misset JL. Pharmacokinetics and safety profile of oxaliplatin. Semin Oncol. 1998;25(2 Suppl 5): 13–22.

2. Lehky TJ, Leonard GD, Wilson RH, Grem JL, Floeter MK. Oxaliplatin-induced neurotoxicity: acute hyperexcitability and chronic neuropathy. Muscle Nerve. 2004;29: 387–392. doi: 10.1002/mus.10559 14981738

3. Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol. 2010;9:807–819. doi: 10.1016/S1474-4422(10)70143-5 20650402

4. St John Smith E. Advances in understanding nociception and neuropathic pain. J Neurol. 2018;265:231–238. doi: 10.1007/s00415-017-8641-6 29032407

5. Grolleau F, Gamelin L, Boisdron-Celle M, Lapied B, Pelhate M, Gamelin E. A possible explanation for a neurotoxic effect of the anticancer agent oxaliplatin on neuronal voltage-gated sodium channels. J Neurophysiol. 2001;85: 2293–2297. doi: 10.1152/jn.2001.85.5.2293 11353042

6. Sittl R, Lampert A, Huth T, Schuy ET, Link AS, Fleckenstein J, et al. Anticancer drug oxaliplatin induces acute cooling-aggravated neuropathy via sodium channel subtype Na(V)1.6-resurgent and persistent current. Proc Natl Acad Sci U S A. 2012;109: 6704–6709. doi: 10.1073/pnas.1118058109 22493249

7. Deuis JR, Zimmermann K, Romanovsky AA, Possani LD, Cabot PJ, Lewis RJ, et al. An animal model of oxaliplatin-induced cold allodynia reveals a crucial role for Nav1.6 in peripheral pain pathways. Pain. 2013;154: 1749–175 doi: 10.1016/j.pain.2013.05.032 23711479

8. Gauchan P, Andoh T, Kato A, Kuraishi Y. Involvement of increased expression of transient receptor potential melastatin 8 in oxaliplatin-induced cold allodynia in mice. Neurosci Lett. 2009;458: 93–95. doi: 10.1016/j.neulet.2009.04.029 19375484

9. Nassini R, Gees M, Harrison S, De Siena G, Materazzi S, Moretto N, et al. Oxaliplatin elicits mechanical and cold allodynia in rodents via TRPA1 receptor stimulation. Pain. 2011;152: 1621–1631. doi: 10.1016/j.pain.2011.02.051 21481532

10. Descoeur J, Pereira V, Pizzoccaro A, Francois A, Ling B, Maffre V, et al. Oxaliplatin-induced cold hypersensitivity is due to remodelling of ion channel expression in nociceptors. EMBO Mol Med. 2011;3:266–278. doi: 10.1002/emmm.201100134 21438154

11. Kono T, Satomi M, Suno M, Kimura N, Yamazaki H, Furukawa H, et al. Oxaliplatin-induced neurotoxicity involves TRPM8 in the mechanism of acute hypersensitivity to cold sensation. Brain Behav. 2012;2: 68–73. doi: 10.1002/brb3.34 22574275

12. Obata K, Noguchi K. MAPK activation in nociceptive neurons and pain hypersensitivity. Life Sci. 2004;74: 2643–2653. doi: 10.1016/j.lfs.2004.01.007 15041446

13. Ji RR, Gereau RW 4th, Malcangio M, Strichartz GR. MAP kinase and pain. Brain Res Rev. 2009;60: 135–148. doi: 10.1016/j.brainresrev.2008.12.011 19150373

14. Scuteri A, Galimberti A, Maggioni D, Ravasi M, Pasini S, Nicolini G, et al. Role of MAPKs in platinum-induced neuronal apoptosis. Neurotoxicology. 2009;30: 312–319. doi: 10.1016/j.neuro.2009.01.003 19428505

15. Scuteri A, Galimberti A, Ravasi M, Pasini S, Donzelli E, Cavaletti G, et al. NGF protects dorsal root ganglion neurons from oxaliplatin by modulating JNK/Sapk and ERK1/2. Neurosci Lett. 2010;486: 141–145. doi: 10.1016/j.neulet.2010.09.028 20850503

16. Kawashiri T, Egashira N, Watanabe H, Ikegami Y, Hirakawa S, Mihara Y, et al. Prevention of oxaliplatin-induced mechanical allodynia and neurodegeneration by neurotropin in the rat model. Eur J Pain. 2011;15:344–350. doi: 10.1016/j.ejpain.2010.08.006 20829082

17. Lee Y, Pai M, Brederson JD, Wilcox D, Hsieh G, Jarvis MF, et al. Monosodium iodoacetate-induced joint pain is associated with increased phosphorylation of mitogen activated protein kinases in the rat spinal cord. Mol Pain. 2011;7: 39. doi: 10.1186/1744-8069-7-39 21599960

18. Kobayashi A, Shinoda M, Sessle BJ, Honda K, Imamura Y, Hitomi S, et al. Mechanisms involved in extraterritorial facial pain following cervical spinal nerve injury in rats. Mol Pain. 2011;7: 12. doi: 10.1186/1744-8069-7-12 21310020

19. Tanaka N, Yamaga M, Tateyama S, Uno T, Tsuneyoshi I, Takasaki M. The effect of pulsed radiofrequency current on mechanical allodynia induced with resiniferatoxin in rats. Anesth Analg. 2010;111: 784–790. doi: 10.1213/ANE.0b013e3181e9f62f 20601454

20. Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9: 671–675. doi: 10.1038/nmeth.2089 22930834

21. Siniscalco D, Giordano C, Rossi F, Maione S, de Novellis V. Role of neurotrophins in neuropathic pain. Curr Neuropharmacol. 2011;9: 523–529. doi: 10.2174/157015911798376208 22654713

22. Tsubaki M, Takeda T, Tani T, Shimaoka H, Suzuyama N, Sakamoto K, et al. PKC/MEK inhibitors suppress oxaliplatin-induced neuropathy and potentiate the antitumor effects. Int J Cancer. 2015;137: 243–250. doi: 10.1002/ijc.29367 25430564

23. Yeo JH, Yoon SY, Kim SJ, Oh SB, Lee JH, Beitz AJ, et al. Clonidine, an alpha-2 adrenoceptor agonist relieves mechanical allodynia in oxaliplatin-induced neuropathic mice; potentiation by spinal p38 MAPK inhibition without motor dysfunction and hypotension. Int J Cancer. 2016;138: 2466–2476. doi: 10.1002/ijc.29980 26704560

24. Lehky TJ, Leonard GD, Wilson RH, Grem JL, Floeter MK. Oxaliplatin-induced neurotoxicity: acute hyperexcitability and chronic neuropathy. Muscle Nerve. 2004;29: 387–392. doi: 10.1002/mus.10559 14981738

25. Park SB, Goldstein D, Lin CS, Krishnan AV, Friedlander ML, Kiernan MC. Acute abnormalities of sensory nerve function associated with oxaliplatin-induced neurotoxicity. J Clin Oncol. 2009;27: 1243–1239. doi: 10.1200/JCO.2008.19.3425 19164207

26. Adelsberger H, Quasthoff S, Grosskreutz J, Lepier A, Eckel F, Lersch C. The chemotherapeutic oxaliplatin alters voltage-gated Na+ channel kinetics on rat sensory neurons. Eur J Pharmacol. 2000;40: 25–32.

27. Webster RG, Brain KL, Wilson RH, Grem JL, Vincent A. Oxaliplatin induces hyperexcitability at motor and autonomic neuromuscular junctions through effects on voltage-gated sodium channels. Br J Pharmacol. 2005;146: 1027–39. doi: 10.1038/sj.bjp.0706407 16231011

28. Kagiava A, Tsingotjidou A, Emmanouilides C, Theophilidis G. The effects of oxaliplatin, an anticancer drug, on potassium channels of the peripheral myelinated nerve fibres of the adult rat. Neurotoxicology. 2008;29: 1100–1106. doi: 10.1016/j.neuro.2008.09.005 18845186

29. Sittl R, Carr RW, Fleckenstein J, Grafe P. Enhancement of axonal potassium conductance reduces nerve hyperexcitability in an in vitro model of oxaliplatin-induced acute neuropathy. Neurotoxicology. 2010;31: 694–700. doi: 10.1016/j.neuro.2010.07.006 20670646

30. Benoit E, Brienza S, Dubois JM. Oxaliplatin an anticancer agent that affects both Na+ and K+ channels in frog peripheral myelinated axons. Gen Physiol Biophys. 2006;25: 263–276. 17197725

31. Wu SN, Chen BS, Wu YH, Peng H, Chen LT. The mechanism of the actions of oxaliplatin on ion currents and action potentials in differentiated NG108-15 neuronal cells. Neurotoxicology. 2009;30: 677–685. doi: 10.1016/j.neuro.2009.04.010 19422847

32. Minett MS, Falk S, Santana-Varela S, Bogdanov YD, Nassar MA, Heegaard AM, et al. Pain without nociceptors? Nav1.7-independent pain mechanisms. Cell Rep. 2014;6: 301–312. doi: 10.1016/j.celrep.2013.12.033 24440715

33. Li L, Shao J, Wang J, Liu Y, Zhang Y, Zhang M, et al. MiR-30b-5p attenuates oxaliplatin-induced peripheral neuropathic pain through the voltage-gated sodium channel Nav1.6 in rats. Neuropharmacology. 2019;153:111–120. doi: 10.1016/j.neuropharm.2019.04.024 31054938

34. Wang YS, Li YY, Cui W, Li LB, Zhang ZC, Tian BP, et al. Melatonin Attenuates Pain Hypersensitivity and Decreases Astrocyte-Mediated Spinal Neuroinflammation in a Rat Model of Oxaliplatin-Induced Pain. Inflammation. 2017;40: 2052–2061. doi: 10.1007/s10753-017-0645-y 28812173

35. Illias AM, Gist AC, Zhang H, Kosturakis AK, Dougherty PM. Chemokine CCL2 and its receptor CCR2 in the dorsal root ganglion contribute to oxaliplatin-induced mechanical hypersensitivity. Pain. 2018;159:1308–1316. doi: 10.1097/j.pain.0000000000001212 29554018

36. Huang W, Huang J, Jiang Y, Huang X, Xing W, He Y, et al. Oxaliplatin regulates chemotherapy induced peripheral neuropathic pain in the dorsal horn and dorsal root ganglion via the calcineurin/NFAT Pathway. Anticancer Agents Med Chem. 2018;18:1197–1207. doi: 10.2174/1871520618666180525091158 29793414

37. Wang J, Zhang XS, Tao R, Zhang J, Liu L, Jiang YH, et al. Upregulation of CX3CL1 mediated by NF-κB activation in dorsal root ganglion contributes to peripheral sensitization and chronic pain induced by oxaliplatin administration. Mol Pain. 2017;13: 1744806917726256. doi: 10.1177/1744806917726256 28849713

38. Duan Z, Su Z, Wang H, Pang X. Involvement of pro-inflammation signal pathway in inhibitory effects of rapamycin on oxaliplatin-induced neuropathic pain. Mol Pain. 2018;14: 1744806918769426. doi: 10.1177/1744806918769426 29587559

39. Xu D, Zhao H, Gao H, Zhao H, Liu D, Li J. Participation of pro-inflammatory cytokines in neuropathic pain evoked by chemotherapeutic oxaliplatin via central GABAergic pathway. Mol Pain. 2018;14: 1744806918783535. doi: 10.1177/1744806918783535 29900804

40. Liu ZH, Miao GS, Wang JN, Yang CX, Fu ZJ, Sun T. Resolvin D1 Inhibits Mechanical Hypersensitivity in Sciatica by Modulating the Expression of Nuclear Factor-κB, Phospho-extracellular Signal-regulated Kinase, and Pro- and Anti-inflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion. Anesthesiology. 2016;124: 934–944. doi: 10.1097/ALN.0000000000001010 26808633

41. Jin X, Gereau RW 4th. Acute p38-mediated modulation of tetrodotoxin-resistant sodium channels in mouse sensory neurons by tumor necrosis factor-α. J Neurosci. 2006;26: 246–255. doi: 10.1523/JNEUROSCI.3858-05.2006 16399694

42. Xu JT, Xin WJ, Wei XH, Wu CY, Ge YX, Liu YL, et al. p38 activation in uninjured primary afferent neurons and in spinal microglia contributes to the development of neuropathic pain induced by selective motor fiber injury. Exp Neurol. 2007;204: 355–365. doi: 10.1016/j.expneurol.2006.11.016 17258708

43. Stamboulian S, Choi JS, Ahn HS, Chang YW, Tyrrell L, Black JA, et al. ERK1/2 mitogen-activated protein kinase phosphorylates sodium channel Na(v)1.7 and alters its gating properties. J Neurosci. 2010;30: 1637–1647. doi: 10.1523/JNEUROSCI.4872-09.2010 20130174

44. Nemoto T, Miyazaki S, Kanai T, Maruta T, Satoh S, Yoshikawa N, et al. NaV1.7-Ca2+ influx-induced increased phosphorylations of extracellular signal-regulated kinase (ERK) and p38 attenuate tau phosphorylation via glycogen synthase kinase-3β: priming of NaV1.7 gating by ERK and p38. Eur J Pharmacol. 2010;640: 20–28. doi: 10.1016/j.ejphar.2010.04.048 20470771


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