title: Effects of intrathecally administerd NaV1. 8 antisense oligonucleotide on the expression of sodium channel mRNA in dorsal root ganglion.
abstract: Neuropathic pain has been hypothesized to be the result of aberrant expression and function of sodium channels at the site of injury. To investigate the effects of NaV1. 8 antisense oligonucleotide on the expression of sodium channel mRNA in dorsal root ganglion (DRG) neurons in chronic neuropathic pain. 24 Sprague-Dawley rats weighing 200-260 g were anesthetized with the intraperitoneal injection of 300 mg x kg(-1) choral hydrate. The CCI model was made by loose ligation of sciatic nerve trunk by 4-0 chromic gut. The mechanical and thermal pain threshold were measured before operation and 1, 3, 5, 7, 9, 11, 13 days after operation. A PE-10 catheter was implanted in subarachnoid space at lumbar region. On the 7th postoperative day the animals were randomly divided into 4 groups. The drugs were injected intrathecally twice a day for 5 consecutive days in group 2-4. The animals were decapitated 14 days after the surgery. The L4-L6 DRG of the operated side was removed and crushed, and total RNA was extracted with Trizol reagent. The contralateral side was used as control. The change of NaV1. 8 sodium channel transcripts was determined by RT-PCR. Pain threshold was significantly lowered after CCI as compared with that in control group and was elevated 3 days after antisense oligonucleotide injection. Sensory neuron specific TTX-R sodium channel NaV1. 8 transcript was down-regulated after antisense oligonucleotide injection at the dosage of 45 microg as compared with that in CCI group (P < 0.01), and it was even greater at the dosage of 90 microg. The intrathecally injected NaV1. 8 antisense oligonucleotide can reduce the mechanical allodynia and thermal hyperalgesia partially by downregulating the SNS transcript expression.
authors.affiliation: Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Liu
authors.forename: Shanglong
authors.initials: S
authors.lastname: Yao
authors.forename: Wenge
authors.initials: W
authors.lastname: Song
authors.forename: Yuelan
authors.initials: Y
authors.lastname: Wang
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.forename: Lian
authors.initials: L
authors.lastname: Zen
mesh_terms: D000818:Animals; D005727:Ganglia, Spinal / Q000378:metabolism*; D007278:Injections, Spinal; D008297:Male; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism*; D009619:Nociceptors / Q000503:physiopathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D017288:Pain Threshold; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries / Q000503:physiopathology; D015222:Sodium Channels / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology
chemical_list: D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; C568319:Scn10a protein, rat; D015222:Sodium Channels