The time-course and RNA interference of TNF-alpha, IL-6, and IL-1 beta expression on neuropathic pain induced by L5 spinal nerve transection in rats

被引：22
作者：
Choi, Byung Moon [1 ]
Lee, Soo Han [2 ]
An, Sang Mee [1 ]
Park, Do Yang [2 ]
Lee, Gwan Woo [3 ]
Noh, Gyu-Jeong [1 ,2 ]
机构：
[1] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Anesthesiol & Pain Med, 88,Olympic Ro 43-Gil, Seoul 138736, South Korea
[2] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Clin Pharmacol & Therapeut, Seoul 138736, South Korea
[3] Dankook Univ, Coll Med, Dept Anesthesiol & Pain Med, Cheonan, South Korea
来源：
KOREAN JOURNAL OF ANESTHESIOLOGY | 2015年 / 68卷 / 02期
关键词：
Cytokine; Neuropathic pain; RNA interference;
D O I：
10.4097/kjae.2015.68.2.159
中图分类号：
R614 [麻醉学];
学科分类号：
100217 ;
摘要：
Background: The objective of this study was to investigate the time-course of the expression of TNF-alpha, IL-6, and IL-1 beta after L5 spinal nerve transection (SNT), and to determine the effect of small interfering RNA (siRNA) targeting these cytokines on neuropathic pain. Methods: Rats received control siRNA (CON group, n = 80) or a cocktail of siRNAs targeting these cytokines (COCK group, n = 70). The siRNAs were given via intrathecal catheter 1 d prior to SNT, on the operation day, and 1, 2 and 3 d postoperatively. Behavioral tests and levels of the cytokine mRNAs and proteins as well as glial cell activity were following the L5 SNT. Results: In the CON group, TNF-alpha and IL-1 beta mRNA levels increased immediately after SNT and remained high for 6 d, while IL-6 transcripts only began to increase after 12 h. TNF-alpha and IL-1 beta mRNA levels in the COCK group were lower than in the CON group at all time points (P < 0.05). In the behavioral tests, allodynia and hyperalgesia were significantly lower in the COCK group from 2 d after SNT (P < 0.05). Conclusions: The time courses of TNF-alpha, IL-6 and IL-1 beta mRNA expression after L5 SNT differ. RNA interference may be a method of reducing the development of mechanical allodynia and hyperalgesia in response to nerve injury.
引用
收藏
页码：159 / 169
页数：11
相关论文
共 28 条
[1]   Intrathecal anti-IL-6 antibody and IgG attenuates peripheral nerve injury-induced mechanical allodynia in the rat: possible immune modulation in neuropathic pain [J].
Arruda, JL ;
Sweitzer, SA ;
Rutkowski, MD ;
DeLeo, JA .
BRAIN RESEARCH, 2000, 879 (1-2) :216-225
[2]   3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets [J].
Birmingham, A ;
Anderson, EM ;
Reynolds, A ;
Ilsley-Tyree, D ;
Leake, D ;
Fedorov, Y ;
Baskerville, S ;
Maksimova, E ;
Robinson, K ;
Karpilow, J ;
Marshall, WS ;
Khvorova, A .
NATURE METHODS, 2006, 3 (03) :199-204
[3]   Short interfering RNA (siRNA): tool or therapeutic? [J].
Cejka, D ;
Losert, D ;
Wacheck, V .
CLINICAL SCIENCE, 2006, 110 (01) :47-58
[4]   Discordant protein and mRNA expression in lung adenocarcinomas [J].
Chen, GA ;
Gharib, TG ;
Huang, CC ;
Taylor, JMG ;
Misek, DE ;
Kardia, SLR ;
Giordano, TJ ;
Iannettoni, MD ;
Orringer, MB ;
Hanash, SM ;
Beer, DG .
MOLECULAR & CELLULAR PROTEOMICS, 2002, 1 (04) :304-313
[5]  
Chung JM, 2004, METH MOLEC MED, P35
[6]   The effect of site and type of nerve injury on spinal glial activation and neuropathic pain behavior [J].
Colburn, RW ;
Rickman, AJ ;
DeLeo, JA .
EXPERIMENTAL NEUROLOGY, 1999, 157 (02) :289-304
[7]   Interleukin-6-mediated hyperalgesia/allodynia and increased spinal IL-6 expression in a rat mononeuropathy model [J].
DeLeo, JA ;
Colburn, RW ;
Nichols, M ;
Malhotra, A .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 1996, 16 (09) :695-700
[8]  
Dorazil-Dudzik M, 2004, ANESTH ANALG, V98, P1566, DOI 10.1213/01.ANE.0000113235.88534.48
[9]   siRNA relieves chronic neuropathic pain [J].
Dorn, G ;
Patel, S ;
Wotherspoon, G ;
Hemmings-Mieszczak, M ;
Barclay, J ;
Natt, FJC ;
Martin, P ;
Bevan, S ;
Fox, A ;
Ganju, P ;
Wishart, W ;
Hall, J .
NUCLEIC ACIDS RESEARCH, 2004, 32 (05) :e49
[10]   CUTANEOUS HYPERALGESIA INDUCED BY PERIPHERAL INJECTION OF INTERLEUKIN-1-BETA IN THE RAT [J].
FUKUOKA, H ;
KAWATANI, M ;
HISAMITSU, T ;
TAKESHIGE, C .
BRAIN RESEARCH, 1994, 657 (1-2) :133-140
123