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Activation of Spinal GABAB Receptors Normalizes N‐methyl‐D‐Aspartate Receptor in Diabetic Neuropathy
Author(s) -
Wang XiuLi,
Zhao Xiaonan,
Liu Peng,
Li DePei,
Guo YueXian
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb732
Subject(s) - medicine , gabab receptor , endocrinology , baclofen , nmda receptor , spinal cord , receptor , streptozotocin , neuropathic pain , creb , receptor antagonist , chemistry , agonist , pharmacology , diabetes mellitus , antagonist , biochemistry , psychiatry , transcription factor , gene
N‐methyl‐D‐Aspartate receptor (NMDAR) is increased, while GABA B receptor is decreased in the spinal cord dorsal horn in diabetic neuropathy. In this study, we determined the interaction of NMDAR and GABA B receptors in streptozotocin (STZ)‐induced diabetic neuropathy. The paw withdrawal threshold (PWT) was significantly lower in STZ‐treated rats than in saline‐treated rats. Intrathecal baclofen significantly increased the PWT in STZ‐treated rats, an effect that is abolished by pre‐administration of GABA B receptor specific antagonist CGP55845. Spinal NR2B protein and mRNA expression levels were significantly higher in STZ‐treated rats than in saline‐treated rats. Intrathecal baclofen significantly reduced the NR2B protein and mRNA expression levels in STZ‐treated rats. Intrathecal administration of CGP55845 eliminated baclofen‐induced reduction of protein and mRNA levels in STZ‐treated rats. In addition, the phosphorylated cAMP response element‐binding (CREB) protein levels was significantly higher in spinal cord dorsal horn in STZ‐treated rats. Intrathecal baclofen significantly decreased phosphorylated CREB protein levels in STZ‐treated rats, an effect could be blocked by CGP55845. These data suggest that activation of GABA B receptors in the spinal cord dorsal horn suppresses NMDA receptor expression in diabetic neuropathic pain.