Effects of gabapentin on high-voltage-activated calcium currents in dorsal root ganglion neurons in mice with oxaliplatin-induced neuropathic pain
10.3760/cma.j.issn.0254-1416.2011.06.016
- VernacularTitle:加巴喷丁对奥沙利铂诱发神经病理性痛小鼠背根神经节神经元高电压激活钙通道的影响
- Author:
Jian ZONG
;
Qiang WANG
;
Dan LI
;
Yaomei CUI
;
Hang XIAO
;
Manlin DUAN
- Publication Type:Journal Article
- Keywords:
Cyclohexanecarboxylic acids;
Antineoplastic combined chemotherapy protocols;
Neuralgia;
Calcium channels;
Ganglia,spinal
- From:
Chinese Journal of Anesthesiology
2011;31(6):706-709
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of gabapentin on high-voltage-activated calcium currents in dorsal root ganglion (DRG) neurons in mice with oxaliplatin-induced neuropathic pain (NP). Methods Pathogen-free male Kunming mice aged 6 weeks weighing 20-25 g were used in this study. NP was induced by injection of intraperitoneal oxaliplatin 3 mg/kg. Successful induction of NP was defined as the mechanical paw withdrawal threshold (MWT) measured at 3 d after oxaliplatin administration decreased to 40% of the baseline ( before administration of oxaliplatin). Forty-one mice in which NP was successfully induced were randomly divided into 2 groups: NP group ( n = 20) and gabapentin group (group G, n = 21 ). Another 10 normal mice served as control group (group C). At 3 days after oxaliplatin administration, gabapentin 100 mg/kg was injected intraperitoneally once a day for 3 consecutive days in group G, while C and NP groups received the equal volume of normal saline.MWT to von Fray filament stimulation was measured immediately before and 1-3 days after gabapentin administration (T1-4). After the last measurement of MWT, bilateral L4.5 DRG was collected and neurons were isolated. The high-voltage-activated calcium currents were recorded using whole-cell patch-clamp technique. The peak current density and the voltage where half of the current was activated ( Va1/2 ) or inactivated ( Vi 1/2 ) were calculated. Results Compared with group C, MWT at T1-4 was decreased, the peak current density and Vi1/2 were significantly increased in group NP, and MWT at T1 was decreased in group G ( P ＜ 0.05). There was no significant difference in the peak current density, Vi1/2 and Va1/2 between C and G groups ( P ＞ 0.05). MWT at T2-4 was significantly increased, while the peak current density and Vi1/2 were significantly decreased in group G compared with group NP (P ＜ 0.05). Conclusion Gabapentin can reduce oxaliplatin-induced NP in mice through inhibiting high-voltage-activated calcium currents and promoting the inactivation of the channels in DRG neurons.
