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

NEUROSCIENCE LETTERS

卷:676

Article

Hayashida, Ken-ichiro^1,2  Kimuram, Masafumi²  Eisenach, James C.² 

[1] Akita Univ, Dept Neurophysiol, Sch Med, Akita 0108543, Japan

[2] Wake Forest Sch Med, Dept Anesthesiol, Pain Mech Lab, Winston Salem, NC 27157 USA

关键词: Locus coeruleus;    Endogenous analgesia;    Descending inhibition;    Glutamate;    Noradrenaline;   

DOI  :  10.1016/j.neulet.2018.04.011

来源: Elsevier

【 摘 要 】

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 alpha 2 adrenoceptor antagonist idazoxan or the group 2 metabotropic glutamate receptor (mGluR) antagonist (RS)-alpha-Methyl-4-tetra-zolylphenylglycine (MTPG) increased withdrawal thresholds in SNL animals and this was reversed by the blockade of a-amino-3-hydroxy-5-methyl- 4-isoxazolepropionic acid (AMPA) receptors in the LC or alpha 2-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.

【 授权许可】

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