Activation of spinal GABAB receptors normalizes N-methyl-D-aspartate receptor in diabetic neuropathy.
N-methyl-D-aspartate receptor (NMDAR) activity is increased, while GABAB receptor is downregulated in the spinal cord dorsal horn in diabetic neuropathy. In this study, we determined the interaction of NMDARs and GABAB receptors in streptozotocin (STZ)-induced diabetic neuropathy. The paw withdrawal threshold (PWT) was significantly lower in STZ-treated rats than in vehicle-treated rats. Intrathecal injection of baclofen, a GABAB receptor agonist, significantly increased the PWT in STZ-treated rats, an effect that was abolished by pre-administration of the GABAB receptor specific antagonist CGP55845. Spinal NR2B, an NMDA receptor subunit, protein and mRNA expression levels were significantly higher in STZ-treated rats than in vehicle-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 NR2B protein and mRNA levels in STZ-treated rats. In addition, the phosphorylated cAMP response element-binding (CREB) protein level was significantly higher in the spinal cord dorsal horn in STZ-treated rats compared with vehicle-treated rats. Intrathecal injection of baclofen significantly decreased phosphorylated CREB protein level in STZ-treated rats; an effect was blocked by CGP55845. These data suggest that activation of GABAB receptors in the spinal cord dorsal horn normalizes NMDAR expression level in diabetic neuropathic pain.
Department of Anesthesiology, The Third Hospital of Hebei Medical University, China.
Hui-Ping
HP
Bai
Department of Anesthesiology, The Third Hospital of Hebei Medical University, China.
Peng
P
Liu
Department of Physiology, Hebei Medical University, China.
Yu-Ming
YM
Wu
Department of Anesthesiology, The Third Hospital of Hebei Medical University, China.
Wen-Ya
WY
Guo
Department of Urology, The Third Hospital of Hebei Medical University, China.
Yue-Xian
YX
Guo
Department of Anesthesiology, The Third Hospital of Hebei Medical University, China. Electronic address: wangxl311@126.com.
Xiu-Li
XL
Wang
D000704:Analysis of Variance; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001418:Baclofen / Q000494:pharmacology; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D018756:GABA Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D010721:Phosphinic Acids / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013311:Streptozocin / Q000633:toxicity; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; C121001:NR2B NMDA receptor; D010721:Phosphinic Acids; D011412:Propanolamines; D018080:Receptors, GABA-B; D016194:Receptors, N-Methyl-D-Aspartate; C085075:CGP 55845A; D013311:Streptozocin; D050882:CREB-Binding Protein; D001418:Baclofen
Diabetic neuropathic pain; GABA(B) receptor; Glutamate receptors; Spinal dorsal horn