Blockade of α2-adrenergic or metabotropic glutamate receptors induces glutamate release in the locus coeruleus to activate descending inhibition in rats with chronic neuropathic hypersensitivity.
Blockade of α2-adrenergic or metabotropic glutamate receptors induces glutamate release in the locus coeruleus to activate descending inhibition in rats with chronic neuropathic hypersensitivity.
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DOI：
10.1016/j.neulet.2018.04.011
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发表时间：
2018-05-29
影响因子：
2.5
通讯作者：
Eisenach JC
中科院分区：
文献类型：
--
作者：
Hayashida KI;Kimuram M;Eisenach JC
蓝斑(LC)-脊髓去甲肾上腺素能投射在内源性镇痛机制中起重要作用，并可被LC内的局部谷氨酸信号激活。本研究观察了局部谷氨酸能、GABA能和去甲肾上腺素能对大鼠脊髓神经结扎(SNL)后6周LC谷氨酸释放和去甲肾上腺素下行抑制的影响。LC内注射AMPA-2受体拮抗剂咪唑克生或代谢型谷氨酸受体拮抗剂(RS)-α-甲基-4-四唑苯甘氨酸可提高SNL动物的戒断阈值，这种作用可被阻断脊髓LC或α-2受体的AMPA受体所逆转，但对正常动物无影响。阻断LC中的GABA-A和GABA-B受体均不影响正常和SNL动物的戒断阈值。在SNL动物LC内灌流咪唑克生可增加LC中细胞外谷氨酸的含量，但在正常动物中无此作用。在正常和SNL动物中，LC内灌流MTPG均可增加LC细胞外谷氨酸的含量。这些结果表明，局部去甲肾上腺素和谷氨酸可抑制周围神经损伤后LC内谷氨酸的释放，这可能有助于减轻慢性神经病理性疼痛时对伤害性输入的下行抑制。
Locus coeruleus (LC)-spinal noradrenergic projections are important to endogenous analgesic mechanisms and can be activated by local glutamate signaling in the LC. The current study examined the local glutamatergic, GABAergic, and noradrenergic influences on glutamate release in the LC and noradrenergic descending inhibition in rats 6 weeks after spinal nerve ligation (SNL). Intra-LC injection of the α2 adrenoceptor antagonist idazoxan or the group 2 metabotropic glutamate receptor (mGluR) antagonist (RS)-α-Methyl-4-tetrazolylphenylglycine (MTPG) increased withdrawal thresholds in SNL animals and this was reversed by the blockade of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the LC or α2-adrenoceptors in the spinal cord, but not in normal animals. Neither blockade of GABA-A nor GABA-B receptors in the LC affected withdrawal thresholds in normal and SNL animals. Intra-LC perfusion of idazoxan increased extracellular glutamate in the LC in SNL animals but not in normal animals. Intra-LC perfusion of MTPG increased extracellular glutamate in the LC in both normal and SNL animals. These results suggest that local noradrenaline and glutamate tonically inhibit glutamate release in the LC after peripheral nerve injury and this may contribute to reduced descending inhibition in response to noxious input during chronic neuropathic pain.
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影响因子：
2.5
作者：
Kimura M;Suto T;Eisenach JC;Hayashida K
通讯作者：
Hayashida K
影响因子：
8.8
作者：
Hayashida K;Kimura M;Yoshizumi M;Hobo S;Obata H;Eisenach JC
通讯作者：
Eisenach JC
影响因子：
10.6
作者：
Alba-Delgado, Cristina;Llorca-Torralba, Meritxell;Berrocoso, Esther
通讯作者：
Berrocoso, Esther
影响因子：
1.6
作者：
Mirzaii-Dizgah, Iraj;Karimian, Seyed Morteza;Ghasemi, Tayeb
通讯作者：
Ghasemi, Tayeb
影响因子：
4.7
作者：
Suto, Takashi;Severino, Amie L.;Hayashida, Ken-ichiro
通讯作者：
Hayashida, Ken-ichiro