TY - JOUR
T1 - Altered discharges of spinal neurons parallel the behavioral phenotype shown by rats with bortezomib related chemotherapy induced peripheral neuropathy
AU - Robinson, Caleb R.
AU - Zhang, Hongmei
AU - Dougherty, Patrick M.
N1 - Funding Information:
This work was supported by NIH grant NS046606 and NCI grant CA124787 and the H-E-B Professorship in Cancer Research .
Publisher Copyright:
© 2014 Elsevier B.V. All rights reserved.
PY - 2014
Y1 - 2014
N2 - Bortezomib is a first generation proteasome inhibitor that is the frontline chemotherapy for multiple myeloma with the chief dose-limiting side effect of painful peripheral neuropathy. The goal of this study was to define the behavioral phenotype in a preclinical model of bortezomib chemotherapy-induced peripheral neuropathy (CIPN) and to test whether this is matched by changes in the physiological responses of spinal wide dynamic range neurons. Sprague-Dawley rats were treated with four injections of bortezomib at four doses, 0.05 mg/kg, 0.10 mg/kg, 0.15 mg/kg, 0.20 mg/kg, or equal volume of saline. All doses of bortezomib above 0.05 mg/kg produced showed significant dose-dependent mechanical hyperalgesia that was fully established at 30 days after treatment and that recovered to baseline levels by day 69 after treatment. Thermal, cold, and motor testing were all unaffected by treatment with bortezomib. Spinal wide dynamic range (WDR) neurons in rats with confirmed bortzomib-related CIPN showed an increase in number of evoked discharges to mechanical stimuli and exaggerated after-discharges in rats with bortezomib CIPN.
AB - Bortezomib is a first generation proteasome inhibitor that is the frontline chemotherapy for multiple myeloma with the chief dose-limiting side effect of painful peripheral neuropathy. The goal of this study was to define the behavioral phenotype in a preclinical model of bortezomib chemotherapy-induced peripheral neuropathy (CIPN) and to test whether this is matched by changes in the physiological responses of spinal wide dynamic range neurons. Sprague-Dawley rats were treated with four injections of bortezomib at four doses, 0.05 mg/kg, 0.10 mg/kg, 0.15 mg/kg, 0.20 mg/kg, or equal volume of saline. All doses of bortezomib above 0.05 mg/kg produced showed significant dose-dependent mechanical hyperalgesia that was fully established at 30 days after treatment and that recovered to baseline levels by day 69 after treatment. Thermal, cold, and motor testing were all unaffected by treatment with bortezomib. Spinal wide dynamic range (WDR) neurons in rats with confirmed bortzomib-related CIPN showed an increase in number of evoked discharges to mechanical stimuli and exaggerated after-discharges in rats with bortezomib CIPN.
KW - Bortezomib
KW - Chemotherapy-induced peripheral
KW - Neuropathy
KW - Wide dynamic range neurons
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U2 - 10.1016/j.brainres.2014.06.013
DO - 10.1016/j.brainres.2014.06.013
M3 - Article
C2 - 24949562
AN - SCOPUS:84925362222
SN - 0006-8993
VL - 1574
SP - 6
EP - 13
JO - Brain Research
JF - Brain Research
ER -