title: Intrathecal baclofen, a GABAB receptor agonist, inhibits the expression of p-CREB and NR2B in the spinal dorsal horn in rats with diabetic neuropathic pain.
abstract: This study aimed to investigate the effect of baclofen, a γ-aminobutyric acid B (GABAB) receptor agonist, on the expression of p-CREB and NR2B in the spinal dorsal horn of rats with diabetic neuropathic pain (DNP). The DNP rats, which were successfully induced with streptozocin, were distributed among 3 groups that were treated with saline (D1 group), baclofen (D2 group), or CGP55845 + baclofen (D3 group) continuously for 4 days. The rats induced with saline and subsequently treated with saline were used as controls (C group). The times for the paw withdrawal threshold and thermal withdrawal latency of the D1 group were lower than those for the C group, and were significantly increased after baclofen treatment, but not when GABA receptor was pre-blocked with CGP55845 (D3 group). Increased protein expression levels of NR2B and p-CREB and mRNA levels of NR2B were found in the D1 group when compared with the controls. Baclofen treatment significantly suppressed their expression, bringing it close to the levels of controls. However, in the D3 group, the expression of p-CREB and NR2B were still significantly higher than that of the controls. Activation of GABAB receptor by baclofen attenuates diabetic neuropathic pain, which may partly be accomplished via down-regulating the expression of p-CREB and NR2B.
authors.affiliation: a Department of Anesthesiology, The Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Wen-Ya
authors.initials: WY
authors.lastname: Guo
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Zhao
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Bai
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Wang
authors.forename: Ying-Ze
authors.initials: YZ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology* / Q000627:therapeutic use; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000378:metabolism* / Q000503:physiopathology; D058786:GABA-B Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology; D015870:Gene Expression; D007278:Injections, Spinal; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010147:Pain Measurement; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects* / Q000378:metabolism
chemical_list: D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D050882:CREB-Binding Protein; D001418:Baclofen
keywords: N-methyl-d-aspartate receptor; cyclic adenosine monophosphate response element binding protein; diabetic neuropathic pain; douleur neuropathique diabétique; protéine liant l’élément de réponse à l’adénosine monophosphate cyclique; récepteur de l’acide γ-aminobutyrique; récepteur du N-méthyl-d-aspartate; γ-aminobutyric acid receptor