Painful neuropathy alters the effect of gabapentin on sensory neuron excitability in rats

被引:21
作者
Kanai, A
Sarantopoulos, C
McCallum, JB
Hogan, Q
机构
[1] Kitasato Univ Med, Dept Anesthesiol, Sagamihara, Kanagawa, Japan
[2] Med Coll Wisconsin, Dept Anesthesiol, Milwaukee, WI 53226 USA
关键词
gabapentin; nerve injury; neuronal excitability; neuropathic pain;
D O I
10.1111/j.1399-6576.2004.00356.x
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Background: Pain following peripheral nerve injury is associated with increased excitability of sensory neurons. Gabapentin (GBP), a novel anticonvulsant with an uncertain mechanism of action, is an effective treatment for neuropathic pain. We therefore investigated the effect of GBP on dorsal root ganglion (DRG) neurons from normal rats and those with painful peripheral nerve injury. Methods: Dorsal root ganglions were excised from rats with neuropathic pain behaviour following chronic constriction injury (CCI) of the-sciatic nerve, and from normal rats. Intercellular recordings were made from myelinated sensory neuron somata using a microelectrode technique from DRGs bathed in artificial CSF with or without GBP (100 muM). Results: Compared with normal neurons, injury decreased the refractory interval (RI) for repeat action potential (AP) generation increased the number of APs during sustained depolarization, and shortened the after hyperpolarization following an AP In normal neurons, GBP decreased the RI and increased the AP number during sustained depolarization. In an opposite fashion, the result of GBP application to injured neurons was a decreased number of APs during depolarization and no change in RI. In injured neurons only, GBP increased the time-to-peak for AP depolarization. Conclusions: Nerve injury by CCI is associated with increased sensory neuron excitability, associated with a decreased AHP. In normal peripheral sensory neurons, GBP has pro-excitatory effects, whereas GBP decreases excitability in injured neurons, possibly on the basis of altered sodium channel function.
引用
收藏
页码:507 / 512
页数:6
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