title: Intrathecal administration of cyclic AMP response element-binding protein-antisense oligonucleotide attenuates neuropathic pain after peripheral nerve injury and decreases the expression of N-methyl-D-aspartic receptors in mice.
abstract: The aim of the present study was to determine whether the cAMP response element binding protein (CREB) contributes to neuropathic pain during development stage. Adult (7-8 weeks old) male C57BL/6 mice weighing 20-25 g were used. Intrathecal catheter implantation and chronic constriction of the sciatic nerve of the animals were performed. Western blotting and reverse transcription PCR experiments were carried out. Our study demonstrated that the expression of spinal NMDAR after peripheral nerve injury was modulated by central CREB. Chronic constriction nerve injury (CCI) in mice induced thermal hyperalgesia and mechanical allodynia. The increase of NR1 and NR2B subunits of the NMDAR was significantly diminished by intrathecal administration of the CREB antisense oligonucleotide against CREB and pCREB. Additionally, nociceptive behavior induced by CCI was attenuated by intrathecal administration of the CREB antisense oligonucleotide during the period of injection, and the above effects of relieving pain lasted at least 12 days following the last injection. Our results suggested that central functional pCREB may contribute to the development of neuropathic pain and regulate the expression of the NR1 and NR2B subunits of the NMDAR in the process.
authors: Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical Department of Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
authors: Xiaoping
authors: X
authors: Gu
authors: Jinhua
authors: J
authors: Bo
authors: Wei
authors: W
authors: Zhang
authors: Xiaofeng
authors: X
authors: Sun
authors: Juan
authors: J
authors: Zhang
authors: Yan
authors: Y
authors: Yang
authors: Zhengliang
authors: Z
authors: Ma
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism; D006930:Hyperalgesia; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics*; D059348:Peripheral Nerve Injuries / Q000628:therapy; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000378:metabolism*; D012584:Sciatic Nerve / Q000601:surgery; D020426:Sciatic Neuropathy / Q000503:physiopathology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D016376:Oligonucleotides, Antisense; D016194:Receptors, N-Methyl-D-Aspartate