Paclitaxel Causes Electrophysiological Changes in the Anterior Cingulate Cortex via Modulation of the γ-Aminobutyric Acid-ergic System.
| Autor: | Nashawi H; Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Health Sciences Centre, Kuwait University, Jabriya, Kuwait., Masocha W, Edafiogho IO, Kombian SB |
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| Jazyk: | angličtina |
| Zdroj: | Medical principles and practice : international journal of the Kuwait University, Health Science Centre [Med Princ Pract] 2016; Vol. 25 (5), pp. 423-8. Date of Electronic Publication: 2016 Jun 23. |
| DOI: | 10.1159/000447775 |
| Abstrakt: | 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 γ-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 (Emax) than those from untreated rats (p < 0.001). Bath application of GABA (0.4 µM) reversed this effect and returned the excitability to a level similar to control. Pretreatment of the slices with the GABAB receptor blocker CGP 55845 (50 µM) increased Emax 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. (© 2016 S. Karger AG, Basel.) |
| Databáze: | MEDLINE |
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