The role of kainic acid/AMPA and metabotropic glutamate receptors in the regulation of opioid mRNA expression and the onset of pain-related behavior following excitotoxic spinal cord injury
The role of kainic acid/AMPA and metabotropic glutamate receptors in the regulation of opioid mRNA expression and the onset of pain-related behavior following excitotoxic spinal cord injury
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DOI：
10.1016/s0306-4522(01)00134-8
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发表时间：
2001-01-01
期刊：
影响因子：
3.3
通讯作者：
Brewer, KL
中科院分区：
文献类型：
--
作者：
Abraham, KE;McGinty, JF;Brewer, KL
使君子酸椎管内注射。混合红藻氨酸/2-氨基-3-（3-羟基-5-甲基异噻唑-4-基）丙酸和代谢型谷氨酸受体激动剂，产生兴奋性毒性损伤，导致自发性和诱发性疼痛行为的发作以及阿片肽mRNA、前强啡肽原和前脑啡肽原的脊髓和皮质表达的变化。使君子酸诱导的损伤的哪些特征可归因于每种受体亚型的激活尚不清楚。本研究试图确定红藻氨酸/2-氨基-3-甲基-β-D-半乳糖苷酶的激活作用，通过比较使君子酸诱导的变化与共同注射使君子酸和红藻氨酸产生的变化，研究3-羟基-5-甲基异恶唑-4-基）酸（AMPA）和代谢型谷氨酸受体亚型在兴奋性毒性脊髓损伤后阿片肽表达和自发性及诱发性疼痛相关行为发生中的调节作用。AMPA拮抗剂2，3-二羟基-6-硝基-7-氨磺酰基苯并[f]喹喔啉（NBQX）或代谢型拮抗剂IRS）-1-氨基茚满-1，5-二羧酸（AIDA）。因此，将42只雄性Long Evans成年大鼠分为7个治疗组，并接受脊柱内微量注射生理盐水（假手术）。0.5%二甲亚砜（假）、使君子酸（1.2穆尔，125 mM）、NBQX（1.2穆尔，125 mM）。60 μ M）。AIDA（1.2穆尔。250 μ M）、使君子酸/ NBQX（1.2穆尔. 125 mM/60 μ M），或使君子酸/AIDA（1.2穆尔，125 mM/250 μ M），直接作用于脊髓水平胸12-腰2。自发性和诱发性疼痛反应的行为观察在手术后完成。10天存活期后，处死动物，取出脑和脊髓组织，进行组织学分析和原位杂交。AIDA和NBQX均影响使君子酸诱导的总病变体积，但仅AIDA引起病变中心组织损伤百分比降低。前强啡肽原和前脑啡肽原的表达增加，在脊髓和皮质区使君子酸注射的动物与假，NBQX或艾滋病注射的动物。NBQX不影响使君子酸诱导的脊髓或皮质的前强啡肽原或前脑啡肽原的表达，除了在脊髓前脑啡肽原的表达显着减少。与此相反，AIDA显着降低使君子酸诱导的前强啡肽原和前脑啡肽原在脊髓和皮质内的表达。艾达从这些数据中，我们认为红藻氨酸/AMPA和代谢型谷氨酸受体亚型都参与了使君子酸诱导的神经元损伤和阿片肽mRNA表达变化的兴奋性毒性级联反应的诱导，而代谢型谷氨酸受体可能在损伤后疼痛相关行为的发生中起更重要的作用。(C)2001年IBRO。由Elsevier Science Ltd.出版，版权所有。
Intraspinal injection of quisqualic acid. a mixed kainic acid/2-amino-3(3-hydroxy-5-methylisonazol-4-yl) pionic acid and metabotropic glutamate receptor agonist, produces an excitotoxic injury that leads to the onset of both spontaneous and evoked pain behavior as well as changes in spinal and cortical expression of opioid peptide mRNA, preprodynorphin and preproenkephalin. What characteristics of the quisqualic acid-induced injury are attributable to activation of each receptor subtype is unknown. This study attempted to define the role of activation of the kainic acid/2-amino-3(3-hydroxy-5-methylisoxazol-4-yl) acid (AMPA) and metabotropic glutamate receptor subtypes in the regulation of opioid peptide expression and the onset of spontaneous and evoked pain-related behavior following excitotoxic spinal cord injury by comparing quisqualic acid-induced changes with those created by co-injection of quisqualic acid and the kainic acid/AMPA antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo[f]quinoxaline, (NBQX) or the metabotropic antagonist, IRS)-1-aminoindan-1,5-dicarboxylic acid (AIDA). Therefore, 42 male Long Evans adult rats were divided into seven treatment groups and received intraspinal microinjections of saline (sham). 0.5% dimethylsulphoxide (sham), quisqualic acid (1.2 mul, 125 mM), NBQX (1.2 mul. 60 muM). AIDA (1.2 mul. 250 muM), quisqualic acid/ NBQX (1.2 mul. 125 mM/60 muM), or quisqualic acid/AIDA (1.2 mul, 125 mM/250 muM) directed at spinal levels thoracic 12-lumbar 2. Behavioral observations of spontaneous and evoked pain responses were completed following surgery. After a 10-day survival period, animals were killed and brain and spinal cord tissues were removed and processed for histologic analysis and in situ hybridization. Both AIDA and NBQX affected the quisqualic acid-induced total lesion volume but only AIDA caused a decrease in the percent tissue damage at the lesion epicenter. Preprodynorphin and preproenkephalin expression is increased in both spinal and cortical areas in quisqualic acid-injected animals versus sham-, NBQX or AIDA-injected animals. NBQX did not affect quisqualic acid-induced spinal or cortical expression of preprodynorphin or preproenkephalin except for a significant decrease in preproenkephalin expression in the spinal cord. In contrast, AIDA significantly decreases quisqualic acid-induced preprodynorphin and preproenkephalin expression within the spinal cord and cortex. AIDA. but not NBQX, significantly reduced the frequency of, and delayed the onset of, quisqualic acid-induced spontaneous pain-related behavior.From these data we suggest that both the kainic acid/AMPA and metabotropic glutamate receptor subtypes are involved in the induction of the excitotoxic cascade responsible for quisqualic acid-induced neuronal damage and changes in opioid peptide mRNA expression, while metabotropic glutamate receptors may play a more significant role in the onset of post-injury pain-related behavior. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.