The analgesic effect of intrathecal PKC? antisense oligonucleotide in a rat model of chronic neuropathic pain
- VernacularTitle:鞘内注射反义蛋白激酶C?寡核苷酸对慢性神经痛大鼠的镇痛作用
- Author:
Li WAN
;
Ailin WO
;
Yuke TIAN
- Publication Type:Journal Article
- Keywords:
Protein kinase C;
Oligonucleotides,antisense;
Pain mesurement
- From:
Chinese Journal of Anesthesiology
1994;0(01):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the effect of PKC? antisense oligonucleotide (ASODN) administered intrathecally on the hyperalgesia induced by chronic constructive injury (CCI) and to investigate the underlying mechanism.Methods Twenty four female SD rats weighing 150-180 g were used. CCI was produced by 4 loose ligatures placed on the right sciatic nerve. A catheter was inserted into subarachnoid space at L3-4 for intrathecal drug or normal saline(NS) administration. Three days after intrathecal catheter implantation when the function of the animal's lower limbs recovered, NS or drug was injected through the catheter every day for 6 days. Then the animals were decapitated and the lumbar segment (L2-6 ) of the spinal cord was removed. The animals were randomly divided into 4 groups of 6 animals : Ⅰ CCI + NS (group C); Ⅱ CCI + PKC? sense oligonucleotide (SOON) 20 ?g (group S); Ⅲ CCI + ASODN 5 ?g (group A1) and Ⅳ CCI + ASODN 20 ?g(group A2). The mechanical withdrawal threshold was assessed by Von Frey hair stimulation. The expression of PKC? and PKCa protein in the spinal cord was determined using Western blot. Results The threshold to Von Frey hair stimulation was significantly reduced after sciatic nerve ligation. Intrathecal ASODN administration significantly reduced the hyperalgesia induced by CCI in group A1 and A2 in a dose-dependent manner as compared with group C. The expression of PKCy protein in lumbar spinal cord was significantly lower in group A1 and A2 than in group C. There was no significant difference in PKCa protein expression among the four groups. Conclusion The hyperalgesia induced by CCI can be decreased by intrathecal administration of PKCy antisense oligonucleotide. The reduction in expression of PKCy protein may be involved in the mechanism.
