Chemotherapy Induced Peripheral Neurotoxicity (CIPN) is a long-lasting/permanent adverse event of many anticancer drugs. No cure is available. One reason is uncomplete pathogenesis knowledge: preclinical studies are warranted. However, it is not easy to translate preclinical data into clinical trials; human readouts are needed. Neurophysiology could be a translational outcome measure. Our study was aimed to implement more accurate sensory recordings. Forty female BALB/c mice were divided into 4 groups: naïve (group A, n=10), oxaliplatin-treated (group B, n=10), paclitaxel-treated (group C, n=10), bortezomib-treated (group D, n=10). Neurophysiology was performed at base line and at chemotherapy completion in all groups. At the end of chemotherapy group C and D were sacrificed for histopathological determinations. Group A and D underwent a prolonged period of observation; neurophysiology was repeated at 3, 6, 9 weeks of follow-up. Animals were then sacrificed for neuropathological determinations. Nerve conduction studies were performed for caudal and digital nerves under deep isoflurane anesthesia (body temperature was monitored and kept constant). At the end of treatment all groups showed a significant decrease in SAP amplitudes compared to controls (p-values for caudal and digital nerves respectively in group B:0.0012 and <0.0001; group C:0.0002 and <0.0001; group D: 0.0006 and <0.0001); also, NCV was decreased (p-values for caudal and digital nerves respectively in: group B 0.002 and<0.0001; group C 0.001 and <0.0001; group D 0.0001 and <0.0001). At 3 week follow-up SAP amplitudes between controls and group B showed these p-values for caudal and digital nerves respectively: 0.0020 and 0.0041; NCV showed these p-values for caudal and digital nerves respectively: 0.0002 and 0.022. At 6 week follow-up SAP amplitudes between controls and group B showed these p-values for caudal and digital nerves respectively: 0.0553 and 0.0015; NCV showed these p-values for caudal and digital nerves respectively: 0.0001 and 0.4967. At 9 week follow-up SAP amplitudes between controls and group B showed these p-values for caudal and digital nerves respectively: 0.0053 and 0.6691; NCV showed these p-values for caudal and digital nerves respectively: 0.0031and 0.4002. Data were like natural history in CIPN patients; recordings were consistent with an axonal length-dependent sensory polyneuropathy, since parameters (in particular amplitude) of the most distal nerve, digital one, were the most involved. Oxaliplatin group was observed over time; a moderate recovery was present as known from clinical practice. Our neurophysiological protocol was confirmed to have a high translational potential
Alberti, P., Fumagalli, G., Monza, L., Pozzi, E., Cavaletti, G. (2017). ACCURATE NEUROPHYSIOLOGICAL MONITORING FOR SENSORY NEUROPATHY IN MOUSE MODELS OF CHEMOTHERAPY INDUCED PERIPHERAL NEUROTOXICITY. In Special Issue: Abstracts of the Seventh Annual Meeting of the Associazione Italiana Sistema Nervoso Periferico (ASNP) April 20–22, 2017 Bergamo, Italy (pp.S5-S5).
ACCURATE NEUROPHYSIOLOGICAL MONITORING FOR SENSORY NEUROPATHY IN MOUSE MODELS OF CHEMOTHERAPY INDUCED PERIPHERAL NEUROTOXICITY
ALBERTI, PAOLA;FUMAGALLI, GIULIA;MONZA, LAURA;POZZI, ELEONORA;CAVALETTI, GUIDO ANGELO
2017
Abstract
Chemotherapy Induced Peripheral Neurotoxicity (CIPN) is a long-lasting/permanent adverse event of many anticancer drugs. No cure is available. One reason is uncomplete pathogenesis knowledge: preclinical studies are warranted. However, it is not easy to translate preclinical data into clinical trials; human readouts are needed. Neurophysiology could be a translational outcome measure. Our study was aimed to implement more accurate sensory recordings. Forty female BALB/c mice were divided into 4 groups: naïve (group A, n=10), oxaliplatin-treated (group B, n=10), paclitaxel-treated (group C, n=10), bortezomib-treated (group D, n=10). Neurophysiology was performed at base line and at chemotherapy completion in all groups. At the end of chemotherapy group C and D were sacrificed for histopathological determinations. Group A and D underwent a prolonged period of observation; neurophysiology was repeated at 3, 6, 9 weeks of follow-up. Animals were then sacrificed for neuropathological determinations. Nerve conduction studies were performed for caudal and digital nerves under deep isoflurane anesthesia (body temperature was monitored and kept constant). At the end of treatment all groups showed a significant decrease in SAP amplitudes compared to controls (p-values for caudal and digital nerves respectively in group B:0.0012 and <0.0001; group C:0.0002 and <0.0001; group D: 0.0006 and <0.0001); also, NCV was decreased (p-values for caudal and digital nerves respectively in: group B 0.002 and<0.0001; group C 0.001 and <0.0001; group D 0.0001 and <0.0001). At 3 week follow-up SAP amplitudes between controls and group B showed these p-values for caudal and digital nerves respectively: 0.0020 and 0.0041; NCV showed these p-values for caudal and digital nerves respectively: 0.0002 and 0.022. At 6 week follow-up SAP amplitudes between controls and group B showed these p-values for caudal and digital nerves respectively: 0.0553 and 0.0015; NCV showed these p-values for caudal and digital nerves respectively: 0.0001 and 0.4967. At 9 week follow-up SAP amplitudes between controls and group B showed these p-values for caudal and digital nerves respectively: 0.0053 and 0.6691; NCV showed these p-values for caudal and digital nerves respectively: 0.0031and 0.4002. Data were like natural history in CIPN patients; recordings were consistent with an axonal length-dependent sensory polyneuropathy, since parameters (in particular amplitude) of the most distal nerve, digital one, were the most involved. Oxaliplatin group was observed over time; a moderate recovery was present as known from clinical practice. Our neurophysiological protocol was confirmed to have a high translational potential
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