Spinal GABAA and GABAB receptor pharmacology in a rat model of neuropathic pain
Spinal GABAA and GABAB receptor pharmacology in a rat model of neuropathic pain
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DOI：
10.1097/00000542-200205000-00020
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发表时间：
2002-05-01
期刊：
影响因子：
8.8
通讯作者：
Porreca, F
中科院分区：
文献类型：
--
作者：
Malan, TP;Mata, HP;Porreca, F
背景资料：本研究测试的假设，脊髓活动的损失，T-氨基丁酸（GABA）有助于异常性疼痛和痛觉过敏后观察周围nerveinjure.Methods：鞘内导管植入雄性Sprague-Dawley大鼠。通过测量将尾部浸入52 ℃水浴中的退缩潜伏期来评估抗伤害感受。神经损伤，结扎L5和L 6脊神经产生的血管。在脊神经结扎后4-14天进行测试，此时建立了触觉异常性疼痛和热痛觉过敏。触觉异常性疼痛使用在用von Frey细丝探测时后爪缩回的阈值来定量。使用从辐射热中撤回后爪的潜伏期来定量热痛觉过敏。结果：正常大鼠脊髓注射GABA（A）受体拮抗剂荷包牡丹碱或GABA（B）受体拮抗剂法克氯芬可引起触觉异常性痛和热痛觉过敏。GABA（B）受体激动剂巴氯芬经脊髓给药，在尾-希克试验中产生抗伤害感受，而GABA（A）受体激动剂异谷瓦辛则没有。异古瓦辛和巴氯芬各自逆转脊神经结扎产生的触觉异常性疼痛和热痛觉过敏。巴氯芬而不是异古瓦辛延长热撤退潜伏期在神经损伤大鼠超过术前值。巴氯芬而非异古伐辛损害运动功能。在正常大鼠中，对固有GABA张力的Pliarmacologic抑制导致触觉异常性疼痛和热痛觉过敏，这与正在测试的假设一致。外源性GABA激动剂逆转脊神经结扎引起的异常性疼痛和痛觉过敏，也符合这一假设。异古伐辛产生特异性的抗痛觉过敏和抗异常性疼痛作用，而巴氯芬的作用的评估因运动功能障碍而复杂化。脊髓GABA（A）激动剂可能为神经性疼痛提供特异性治疗。
Background: This study tests the hypothesis that loss of spinal activity, of T-aminobutyric acid (GABA) contributes to the allodynia and hyperalgesia observed after peripheral nerve injury.Methods: Intrathecal catheters were implanted in male Sprague-Dawley rats. Antinociception was assessed by measuring withdrawal latency to immersion of the tail in a 52degreesC water bath. Nerve injury,vas produced by ligation of the L5 and L6 spinal nerves. Testing was performed 4-14 days after spinal nerve ligation, when tactile allodynia and thermal hyperalgesia were established. Tactile allodynia was quantitated using the threshold to withdrawal of the hind paw on probing with von Frey filaments. Thermal hyperalgesia was quantitated using the latency to withdrawal of the hind paw from radiant heat. Motor function was tested using a rotarod apparatus.Results: Spinal administration of the GABA(A) receptor antagonist bicuculline or the GABA(B) receptor antagonist phaclofen produced tactile allodynia and thermal hyperalgesia in normal rats. The GABA(B) receptor agonist baclofen, administered spinally, produced antinociception in the tail-Hick test, whereas the GABA(A) receptor agonist isoguvacine did not. Isoguvacine and baclofen each reversed tactile allodynia and thermal hyperalgesia produced by spinal nerve ligation. Baclofen but not isoguvacine prolonged thermal withdrawal latency in nerve-injured rats beyond preoperative values. Baclofen but not isoguvacine impaired motor function.Conclusions. Pliarmacologic inhibition of intrinsic GABA tone in normal rats resulted in tactile allodynia and thermal hyperalgesia, consistent with the hypothesis being tested. Exogenous administration of GABA agonists reversed spinal nerve ligation-induced allodynia and hyperalgesia, also consistent with this hypothesis. isoguvacine produced specific antihyperalgesic and antiallodynic effects, whereas assessment of the effects of baclofen was complicated by motor dysfunction. Spinal GABA(A) agonists may provide a specific therapy for neuropathic pain.