Intraspinal transplantation of GABAergic neural progenitors attenuates neuropathic pain in rats: a pharmacologic and neurophysiological evaluation.
Intraspinal transplantation of GABAergic neural progenitors attenuates neuropathic pain in rats: a pharmacologic and neurophysiological evaluation.
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DOI：
10.1016/j.expneurol.2011.12.005
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发表时间：
2012-03
影响因子：
5.3
通讯作者：
Sagen, Jacqueline
中科院分区：
文献类型：
--
作者：
Jergova, Stanislava;Hentall, Ian D.;Gajavelli, Shyam;Varghese, Mathew S.;Sagen, Jacqueline
功能障碍的γ-氨基丁酸（GABA）能抑制性神经传递被假设为慢性神经病理性疼痛的基础。GABA能神经前体细胞（NPC）椎管内移植可通过恢复背角抑制来减轻神经病理性疼痛。将预分化为GABA能表型的大鼠NPC移植到单侧坐骨神经慢性压迫性损伤（CCI）大鼠的背角。用GABAA受体拮抗剂荷包牡丹碱（BIC）、GABAB受体拮抗剂CGP 35348（CGP）和GABA再摄取抑制剂SKF 89976 A（SKF）检测了GABA信号通路在NPC移植物抗伤害感受效应中的作用。移植后1-3周，NPC治疗的动物显示出减少的痛觉过敏和异常性疼痛;注射载体的CCI大鼠继续显示疼痛行为。鞘内应用BIC或CGP减弱NPC移植物的抗伤害效应，而对照大鼠注射SKF诱导镇痛。NPC治疗大鼠的电生理记录显示，与对照组相比，宽动态范围（WDR）神经元对外周刺激的反应降低。脊髓应用BIC或CGP增加了NPC治疗动物的WDR神经元的发条反应和后放电。结果表明，GABA能NPC移植减轻疼痛行为，减少CCI诱导的过度背角神经元放电。GABA受体抑制剂的作用表明持续释放的GABA参与移植动物。
Dysfunctional γ-aminobutyric acid (GABA)-ergic inhibitory neurotransmission is hypothesized to underlie chronic neuropathic pain. Intraspinal transplantation of GABAergic neural progenitor cells (NPCs) may reduce neuropathic pain by restoring dorsal horn inhibition. Rat NPCs pre-differentiated to a GABAergic phenotype were transplanted into the dorsal horn of rats with unilateral chronic constriction injury (CCI) of the sciatic nerve. GABA signaling in antinociceptive effects of NPC grafts was tested with the GABAA receptor antagonist bicuculline (BIC), GABAB receptor antagonist CGP35348 (CGP) and GABA reuptake inhibitor SKF 89976A (SKF). NPC-treated animals showed decreased hyperalgesia and allodynia 1-3 week post-transplantation; vehicle-injected CCI rats continued displaying pain behaviors. Intrathecal application of BIC or CGP attenuated the antinociceptive effects of the NPC transplants while SKF injection induced analgesia in control rats. Electrophysiological recordings in NPC treated rats showed reduced responses of wide dynamic range (WDR) neurons to peripheral stimulation compared to controls. A spinal application of BIC or CGP increased wind-up response and post-discharges of WDR neurons in NPC treated animals. Results suggest that transplantation of GABAergic NPCs attenuate pain behaviors and reduce exaggerated dorsal horn neuronal firing induced by CCI. The effects of GABA receptor inhibitors suggest participation of continuously released GABA in the grafted animals.
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