Bortezomib is a proteasome inhibitor that shows a high antineoplastic effects mainly in the treatment of a multiple myeloma. Painful bortezomib-induced peripheral neuropathy represents the dose-limiting factors in its use in clinical practice. To reproduce the clinical pain symptoms, we have established an animal model of bortezomib-induced nociceptive sensory neuropathy. This study was performed by repeated administration of bortezomib in Wistar rats at doses of 0.15-0.20 mg/kg [3q7d] for eight weeks, followed-up by an observation period of 4 weeks. Bortezomib-treated rats had a reduced weight gain at the end of treatment if compared to controls, that recovered after the follow-up period. A significant decrease in the nerve conduction velocity in both doses group was observed after the treatment period. The sensory behavioural assessment, demonstrated the onset of mechanical allodynia after the eight weeks of treatment. Sciatic nerve and DRG specimens, collected at the end of treatment and after the follow-up period, were processed for light and electron microscope analysis to evaluated any pathological alteration on fibers and on dorsal root ganglions (DRG). Morphological evaluation described a dose-dependent axonopathy in treated rats’ sciatic nerves vs. control rats, involving also the unmyelinated fibers. No pathological alteration in most of DRG satellite cells or neurons was observed. This model can be useful for the study on the neurotoxicity and pain onset mechanisms related to the treatment with bortezomib. Supported by grants from the “Fondazione Banca del Monte di Lombardia” and the “Italian Ministry of Health”(Assessment and rehabilitation in patients with chemotherapy-induced peripheral neuropathy)

Meregalli, C., Canta, A., Chiorazzi, A., Gilardini, A., RODRIGUEZ MENENDEZ, V., Bossi, M., et al. (2009). BEHAVIOURAL AND MORPHOLOGICAL DESCRIPTION OF BORTEZOMIB-INDUCED PAINFUL NEUROPATHY IN RATS. In JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM (pp.100-100).

BEHAVIOURAL AND MORPHOLOGICAL DESCRIPTION OF BORTEZOMIB-INDUCED PAINFUL NEUROPATHY IN RATS

MEREGALLI, CRISTINA
;
CANTA, ANNALISA ROSANNA
Secondo
;
CHIORAZZI, ALESSIA;GILARDINI, ALESSANDRA;RODRIGUEZ MENENDEZ, VIRGINIA;BOSSI, MARIO;MARMIROLI, PAOLA LORENA
Penultimo
;
CAVALETTI, GUIDO ANGELO
Primo
2009

Abstract

Bortezomib is a proteasome inhibitor that shows a high antineoplastic effects mainly in the treatment of a multiple myeloma. Painful bortezomib-induced peripheral neuropathy represents the dose-limiting factors in its use in clinical practice. To reproduce the clinical pain symptoms, we have established an animal model of bortezomib-induced nociceptive sensory neuropathy. This study was performed by repeated administration of bortezomib in Wistar rats at doses of 0.15-0.20 mg/kg [3q7d] for eight weeks, followed-up by an observation period of 4 weeks. Bortezomib-treated rats had a reduced weight gain at the end of treatment if compared to controls, that recovered after the follow-up period. A significant decrease in the nerve conduction velocity in both doses group was observed after the treatment period. The sensory behavioural assessment, demonstrated the onset of mechanical allodynia after the eight weeks of treatment. Sciatic nerve and DRG specimens, collected at the end of treatment and after the follow-up period, were processed for light and electron microscope analysis to evaluated any pathological alteration on fibers and on dorsal root ganglions (DRG). Morphological evaluation described a dose-dependent axonopathy in treated rats’ sciatic nerves vs. control rats, involving also the unmyelinated fibers. No pathological alteration in most of DRG satellite cells or neurons was observed. This model can be useful for the study on the neurotoxicity and pain onset mechanisms related to the treatment with bortezomib. Supported by grants from the “Fondazione Banca del Monte di Lombardia” and the “Italian Ministry of Health”(Assessment and rehabilitation in patients with chemotherapy-induced peripheral neuropathy)
abstract + poster
painful neuropathy, bortezomib, rats, morphological and behavioural evaluation
English
Annual Meeting of the Peripheral-Nerve-Society JUL 04-08
2009
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
2009
14
100
100
open
Meregalli, C., Canta, A., Chiorazzi, A., Gilardini, A., RODRIGUEZ MENENDEZ, V., Bossi, M., et al. (2009). BEHAVIOURAL AND MORPHOLOGICAL DESCRIPTION OF BORTEZOMIB-INDUCED PAINFUL NEUROPATHY IN RATS. In JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM (pp.100-100).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/59206
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