Effects of intrathecai Na_V 1.8 antisense oligonucleotide on chronic neuropathic pain in rats / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effects of intrathecal (IT) NaV 1.8 antisense oligonucleotide on the chronic neuropathic pain induced by chronic constrictive injury (CCI) to the sciatic nerve.Methods Twenty-four male SD rats were randomly divided into 4 groups ( n = 6 each) group Ⅰ CCI + NS 5 ?l; group Ⅱ CCI + mismatch oligonucleotide 45 ?g; group ⅢCCI + antisense oligonucleotide 45 ?g and group Ⅳ CCI + antisense oligonucleotide 90 ?g. CCI was produced by placing 4 loose ligatures on the left sciatic nerve at 1 mm interval with 4-0 chromic catgut as described by Bennett. On the 5th day after CCI IT catheter was inserted at the level of lumbar spine and identified by free flow of CSF. On the 8th day after CCI normal saline or mismatch or antisense oligonucleotide was injected IT twice a day for 5 consecutive days. Threshold to noxious thermal and mechanical stimuli was measured before CCI (baseline) and on the 1st, 3rd, 5th, 7th, 9th, 11th and 13th day after CCI. On the 14th day after CCI the lumbar segment of spinal cord was removed for determination of NaV 1.8 sodium channel expression in L4-6 dorsal root ganglion (DRG) by semi-reverse transcriptase-PCR.Results The threshold to von Frey hair stimulation and noxious thermal stimuli on the operated side was significantly lowered after CCI. On the 11th and 13th day after CCI the threshold to mechanical and thermal stimuli were significantly higher in group Ⅲand Ⅳ than in group I and H . Conclusion IT NaV 1. 8 antisense oligonucleotide can reduce the neuropathic pain by down-regulating NaV 1.8 mRNA expression.