Ibudilast reduces oxaliplatin-induced tactile allodynia and cognitive impairments in rats

被引:24
作者
Johnston, Ian N. [1 ]
Tan, Manuela [1 ]
Cao, Jacob [1 ]
Matsos, Antigone [1 ]
Forrest, Daniel R. L. [1 ]
Si, Emily [1 ]
Fardell, Joanna E. [1 ,2 ]
Hutchinson, Mark R. [3 ,4 ]
机构
[1] Univ Sydney, Sch Psychol, A18, Sydney, NSW 2006, Australia
[2] Univ NSW, Sch Womens & Childrens Hlth, Discipline Paediat, Sydney, NSW, Australia
[3] Univ Adelaide, Adelaide Med Sch, Discipline Physiol, Adelaide, SA, Australia
[4] Australian Res Council, Ctr Excellence Nanoscale BioPhoton, Adelaide, SA, Australia
关键词
Oxaliplatin; Chemotherapy; Neuropathic pain; Memory impairment; Ibudilast; INDUCED PERIPHERAL NEUROPATHY; PHOSPHODIESTERASE INHIBITOR; DOUBLE-BLIND; MECHANICAL ALLODYNIA; MEMORY DEFICITS; INTRACELLULAR CALCIUM; MICROGLIAL ACTIVATION; INDUCED NEUROTOXICITY; PAINFUL NEUROPATHY; OPIOID WITHDRAWAL;
D O I
10.1016/j.bbr.2017.07.021
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
Chemotherapy can cause serious neurotoxic side effects, such as painful peripheral neuropathies and disabling cognitive impairments. Four experiments examined whether Ibudilast, a clinically approved neuroimmune therapy, would reduce tactile allodynia and memory impairments caused by oxaliplatin in laboratory rats. Rats received an intraperitoneal injection of oxaliplatin (6 mg/kg i.p.) or vehicle and were assessed for tactile allodynia 3 or 5 days after injection, memory impairments in the novel object and novel location recognition tests 10-12 days after injection, and fear conditioning 14 days after injection. Ibudilast (7.5 mg/kg) or vehicle was administered prior to oxaliplatin (Experiments 1 and 3) or prior to behavioural testing (Experiments 2 and 4). Ibudilast treatment prior to oxaliplatin prevented the development of tactile allodynia and memory impairments. Ibudilast treatment prior to behavioural testing reduced oxaliplatin-induced tactile allodynia, memory impairments, and impaired renewal of fear conditioning. These results suggest that Ibudilast could be an effective treatment against oxaliplatin-induced neuropathies and cognitive impairments.
引用
收藏
页码:109 / 118
页数:10
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