Effects of Oxaliplatin and Cisplatin on Peripheral Nerve Excitability and Conduction
AbstractObjective: This study examines and compares the level of neurotoxicity of oxaliplatin and cisplatin in terms of excitability and conduction parameters over rats’ caudal and sciatic nerves. Methods: Twenty-seven Wistar rats were divided into three groups labeled as oxaliplatin (OXA), cisplatin (CIS) and control (CON). OXA and CIS groups were administered oxaliplatin (8 mg/kg/week, i.p) and cisplatin (4 mg/kg/week, i.p) respectively, for a 4.5 week follow-up period. Shortly after, threshold tracking recordings from tail caudal nerve and compound action potential recordings from isolated sciatic nerve were performed, in order to obtain the corresponding excitability and conduction parameters. Results: Cisplatin is found more neurotoxic than oxaliplatin with regards to nerve excitability and conduction. Cisplatin is more effective on fibers having small radius (slowly conducting). The partial blockade of Na+ channels (mostly persistent) and an increment in the activity of inward rectifier K+ conductance due to cisplatin are noteworthy. Conclusion: In terms of neurotoxicity, oxaliplatin may be more preferable compared to cisplatin clinically.
Gamelin E, Gamelin L, Bossi L, Quasthoff S. Clinical aspects and molecular basis of oxaliplatin neurotoxicity: current management and development of preventive measures. Semin Oncol. 2002;29:21-33.
Holmes J, Stanko J, Varchenko M, Ding H, Madden VJ, Bagnell CR et al. Comparative neurotoxicity of oxaliplatin, cisplatin, and ormaplatin in a wistar rat model. Toxicol Sci. 1998;46(2):342-51.
Amptoulach S, Tsavaris N. Neurotoxicity caused by treatment with platinum analogues. Chemoter Res Pract. 2011;843019.
Park SB, Lin CSY, Krishnan AV, Goldstein D, Friedlander ML, Kiernan MC. Utilizing natural activity to dissect to pathophysiology of acute oxaliplatin-induced neuropathy. J Expneurol. 2011;227(1):120-7.
Tuncer S, Dalkilic N, Dunbar MA, Keles B. Comperative effects of alphalipoic acid and melatonin on cisplatin-induced neurotoxicity. Int Jour Neuro. 2010;120(10):655-63.
Bostock H, Cikurel K, Burke D. Threshold tracking techniques in the study of human peripheral nerve. Muscle Nerve. 1998;21:137–58.
Nodera H, Kaji R. Nerve excitability testing and its clinical application to neuromuscular diseases. Clin Neurophysiol. 2006;117:1902–1916.
Dalkilic N, Pehlivan F. Comparison of fiber diameter distribution deduced by modelling compound action potentials recorded by extracellular and suction techniques. Int J Neurosci. 2002;112(8):913-30a.
Stys PK, Ransom BR, Waxman SG. Compound action potential of nerve recorded by suction electrode: A theoretical and experimental analysis. Brain Res. 1991;12;546(1):18-32.
Krishnan AV, Lin CSY, Park SB, Kiernan MC. Axonal ion channel from bench to bedside: A translational neuroscience perspective. Prog Neurobiol. 2009;89(3):288-313.
Burke D, Kiernan MC, Bostock H. Excitability of human axons. Clin Neurophysiol. 2001;112:1575-1585.
Clay JR. On the persistent sodium current in squid giant axons. J Neurophysiol. 2003;89(1):640-4.
Meisler MH, Kearney JA. Sodium channel mutations in epilepsy and other neurological disorders. J Clin Invest. 2005;115(8):2010-7.
Mogyoros I, Kiernan M, Burke D, Bostock H. Strength-duration properties of sensory and motor axons in amyotrophic lateral sclerosis. Brain. 1998;121;851-859.
George A, Bostock H. Multiple measures of axonal excitability in peripheral sensory nerves: An in vivo rat model. Muscle Nerve. 2007;36(5):628-36.
Bostock H, Lin CS, Howells J, Trevillion L, Jankelowitz S, Burke D. After-effects of near- threshold stimulation in single human motor axons. J Physiol. 2005;1;564(Pt3):931-40.
Tuncer S, Dalkilic N, Esen HH, Avunduk MC. An early diagnostic tool for diabetic neuropathy: Conduction velocity distribution. Muscle Nerve. 2011;43(2):237-44.
Dalkilic N, Pehlivan F. A correction procedure for the volume conductor effect in the compound action potential recorded from isolated nerve trunk. Int J Neurosci. 2002;112:1013–1026b.
Cummins KL, Dorfman LJ, Perkel DH. Nerve fiber conduction-velocity distribution. II. Estimation based on two compound action potentials. Electroencephalogr Clin Neurophysiol. 1979;46:647-658a.
Cummins KL, Perkel DH, Dorfman LJ. Nerve fiber conduction-velocity distribution. I. Estimation based on the single-fiber and compound action potentials. Electroencephalogr Clin Neurophysiol. 1979;46:634-646b.
Pehlivan F. Biyofizik, 8th ed. Ankara : Pelikan Press; 2015.
Vasilescu V, Margineanu DG. Introduction to neurobiophysics. Abacus Press, Kent; 1982.
Huynh W, Kiernan MC. Peripheral nerve axonal excitability studies: expanding the neurophysiologist's armamentarium. Cerebellum Ataxias. 2015;3;2:4.
Tuncer S, Peker TT, Burat I, Kiziltan E, Ilhan B, Dalkilic N. Axonal excitability and conduction alterations caused by levobupivacaine in rat. Acta Pharmaceutica. 2017;xx:xx (in press).
Taddese A, Bean BP. Subthreshold sodium current from rapidly inactivating sodium channels drives spontaneous firing of tuberomammillary neurons. Neuron. 2002;14;33(4):587-600.
Farrar MA, Vucic S, Lin CS, Park SB, Johnston HM, du Sart D et al. Dysfunction of axonal membrane conductances in adolescents and young adults with spinal muscular atrophy. Brain. 2011;134:3185-97.
Tomaszewski A, Busselberg D. Cisplatin modulates voltage gated channel currents of dorsal root ganglion neurons of rats. Neurotoxicology 2007;28(1):49-58.
Franssen H. Relation between symptoms and pathophysiology in inflammatory neuropathies: Controversies and hypotheses. Neurosci Lett. 2015;2;596:84-9.
Ta LE, Espeset L, Podratz J, Windebank AJ. Neurotoxicity of oxaliplatin and cisplatin for dorsal root ganglion neurons correlates with platinum-DNA binding. Neurotoxicology. 2006;27(6):992-1002.
New P, Barohn R, O’Rourke T, Seharaseyan J, Mendell JR, Sahenk Z. Neuropathy following ormaplatin administration: human and laboratory studies. Procasco. 1993;12,155.
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(5):266-78.
Bostock H. Nerve excitability studies: past, present, future? Suppl Clin Neurophysiol. 2004;57:85-90.