Effects of intrathecally administerd NaV1. 8 antisense oligonucleotide on the expression of sodium channel mRNA in dorsal root ganglion.
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.
Liu
Yongmin
Y
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Yao
Shanglong
S
Song
Wenge
W
Wang
Yuelan
Y
Liu
Dong
D
Zen
Lian
L
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
D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; C568319:Scn10a protein, rat; D015222:Sodium Channels