期刊
MEDICAL PRINCIPLES AND PRACTICE
卷 25, 期 5, 页码 423-428出版社
KARGER
DOI: 10.1159/000447775
关键词
Allodynia; gamma-Amino butyric acid; Anterior cingulate cortex; Enaminone; Field excitatory postsynaptic potentials; Paclitaxel-induced neuropathic pain
Objective: The aim of this study was to elucidate any electrophysiological changes that may contribute to the development of neuropathic pain during treatment with the anticancer drug paclitaxel, particularly in the gamma-aminobutyric acid (GABA) system. Materials and Methods: One hundred and eight Sprague-Dawley rats were used (untreated control: 43; vehicle-treated: 21, and paclitaxel-treated: 44). Paclitaxel (8 mg/kg) was administered intraperitoneally on 2 alternate days to induce mechanical allodynia. The rats were sacrificed 7 days after treatment to obtain slices of the anterior cingulate cortex (ACC), a brain region involved in the central processing of pain. Field excitatory postsynaptic potentials (fEPSPs) were recorded in layer II/III of ACC slices, and stimulus-response curves were constructed. The observed effects were pharmacologically characterized by bath application of GABA and appropriate drugs to the slices. Results: The paclitaxel- treated rats developed mechanical allodynia (i.e. reduced withdrawal threshold to mechanical stimuli). Slices from paclitaxel- treated rats produced a significantly higher maximal response (E-max) than those from untreated rats (p < 0.001). Bath application of GABA (0.4 mu M) reversed this effect and returned the excitability to a level similar to control. Pretreatment of the slices with the GABA(B) receptor blocker CGP 55845 ( 50 mu M) increased E-max in slices from untreated rats ( p < 0.01) but not from paclitaxel-treated rats. Conclusion: In this study, there was a GABA deficit in paclitaxel-treated rats compared to untreated ones. Such a deficit could contribute to the pathophysiology of paclitaxel-induced neuropathic pain ( PINP). Thus, the GABAergic system might be a potential therapeutic target for managing PINP. (C) 2016 S. Karger AG, Basel
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