Multimodal assessment of painful peripheral neuropathy induced by chronic oxaliplatin-based chemotherapy in mice
| Autor: | Guido Cavaletti, Danisha Gallop, Valentina Alda Carozzi, Peter Rhee, Cynthia L. Renn, Susan G. Dorsey |
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| Přispěvatelé: | Renn, C, Carozzi, V, Rhee, P, Gallop, D, Dorsey, S, Cavaletti, G |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
peripheral neuropathy
Organoplatinum Compounds Neural Conduction Pharmacology Mice 0302 clinical medicine Ganglia Spinal Medicine Mice Inbred BALB C Peripheral Nervous System Diseases dorsal root ganglia Sciatic Nerve 3. Good health Posterior Horn Cells Oxaliplatin medicine.anatomical_structure Hyperalgesia 030220 oncology & carcinogenesis Peripheral nervous system Anesthesia Neuropathic pain Molecular Medicine Female Sciatic nerve medicine.symptom Cell Nucleolus medicine.drug mechanical allodynia lcsh:RB1-214 Central nervous system Pain cold hyperalgesia Axon 03 medical and health sciences Cellular and Molecular Neuroscience lcsh:Pathology Animals spinal dorsal horn Animal business.industry Research Body Weight Organoplatinum Compound Neurotoxicity medicine.disease electrophysiology digestive system diseases Axons Rats Posterior Horn Cell Cell Nucleolu Anesthesiology and Pain Medicine Peripheral neuropathy Rat Peripheral Nervous System Disease business 030217 neurology & neurosurgery |
| Zdroj: | Molecular Pain, Vol 7, Iss 1, p 29 (2011) Molecular Pain |
| ISSN: | 1744-8069 |
| Popis: | Background: A major clinical issue affecting 10-40% of cancer patients treated with oxaliplatin is severe peripheral neuropathy with symptoms including cold sensitivity and neuropathic pain. Rat models have been used to describe the pathological features of oxaliplatin-induced peripheral neuropathy; however, they are inadequate for parallel studies of oxaliplatin's antineoplastic activity and neurotoxicity because most cancer models are developed in mice. Thus, we characterized the effects of chronic, bi-weekly administration of oxaliplatin in BALB/c mice. We first studied oxaliplatin's effects on the peripheral nervous system by measuring caudal and digital nerve conduction velocities (NCV) followed by ultrastructural and morphometric analyses of dorsal root ganglia (DRG) and sciatic nerves. To further characterize the model, we examined nocifensive behavior and central nervous system excitability by in vivo electrophysiological recording of spinal dorsal horn (SDH) wide dynamic range neurons in oxaliplatin-treated mice Results: We found significantly decreased NCV and action potential amplitude after oxaliplatin treatment along with neuronal atrophy and multinucleolated DRG neurons that have eccentric nucleoli. Oxaliplatin also induced significant mechanical allodynia and cold hyperalgesia, starting from the first week of treatment, and a significant increase in the activity of wide dynamic range neurons in the SDH. Conclusions: Our findings demonstrate that chronic treatment with oxaliplatin produces neurotoxic changes in BALB/c mice, confirming that this model is a suitable tool to conduct further mechanistic studies of oxaliplatin-related antineoplastic activity, peripheral neurotoxicity and pain. Further, this model can be used for the preclinical discovery of new neuroprotective and analgesic compounds. |
| Databáze: | OpenAIRE |
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