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

Choi BM, Lee SH, An SM, Park do Y, Lee GW, Noh GJ - Korean J Anesthesiol (2015)

Bottom Line: Behavioral tests and levels of the cytokine mRNAs and proteins as well as glial cell activity were following the L5 SNT.In the behavioral tests, allodynia and hyperalgesia were significantly lower in the COCK group from 2 d after SNT (P < 0.05).RNA interference may be a method of reducing the development of mechanical allodynia and hyperalgesia in response to nerve injury.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

ABSTRACT

Background: The objective of this study was to investigate the time-course of the expression of TNF-α, IL-6, and IL-1β 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-α and IL-1β mRNA levels increased immediately after SNT and remained high for 6 d, while IL-6 transcripts only began to increase after 12 h. TNF-α and IL-1β 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-α, IL-6 and IL-1β 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.

No MeSH data available.


Related in: MedlinePlus

The time course of mechanical allodynia (A) and hyperalgesia (B) in the ipsilateral hind paw of rats undergoing L5 spinal nerve transection (SNT) after the administration of control siRNA (CON group) or a cocktail of small interfering RNAs (siRNA) targeting TNF-α, IL-6 and IL1-β (COCK group). The data on the rats surviving for 6 d after SNT are expressed as mean ± SE. -1: 1 d prior to SNT, 0: the day of L5 SNT, 1, 2, 4 and 6: 1, 2, 4 and 6 d after L5 SNT. *P < 0.05 vs. CON group at each time point. MPE: maximal possible effect. The cut-off values for mechanical allodynia and hyperalgesia are 30 g and 250 g, respectively.
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Figure 2: The time course of mechanical allodynia (A) and hyperalgesia (B) in the ipsilateral hind paw of rats undergoing L5 spinal nerve transection (SNT) after the administration of control siRNA (CON group) or a cocktail of small interfering RNAs (siRNA) targeting TNF-α, IL-6 and IL1-β (COCK group). The data on the rats surviving for 6 d after SNT are expressed as mean ± SE. -1: 1 d prior to SNT, 0: the day of L5 SNT, 1, 2, 4 and 6: 1, 2, 4 and 6 d after L5 SNT. *P < 0.05 vs. CON group at each time point. MPE: maximal possible effect. The cut-off values for mechanical allodynia and hyperalgesia are 30 g and 250 g, respectively.

Mentions: The changes in mechanically induced allodynia and hyperalgesia in the rats surviving for 6 d after SNT are shown in Fig. 2. Allodynia and hyperalgesia were lower in the COCK group than in the CON group by 2 d after SNT (P < 0.05) and the difference was maintained for the duration of the experiment.


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

Choi BM, Lee SH, An SM, Park do Y, Lee GW, Noh GJ - Korean J Anesthesiol (2015)

The time course of mechanical allodynia (A) and hyperalgesia (B) in the ipsilateral hind paw of rats undergoing L5 spinal nerve transection (SNT) after the administration of control siRNA (CON group) or a cocktail of small interfering RNAs (siRNA) targeting TNF-α, IL-6 and IL1-β (COCK group). The data on the rats surviving for 6 d after SNT are expressed as mean ± SE. -1: 1 d prior to SNT, 0: the day of L5 SNT, 1, 2, 4 and 6: 1, 2, 4 and 6 d after L5 SNT. *P < 0.05 vs. CON group at each time point. MPE: maximal possible effect. The cut-off values for mechanical allodynia and hyperalgesia are 30 g and 250 g, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4384404&req=5

Figure 2: The time course of mechanical allodynia (A) and hyperalgesia (B) in the ipsilateral hind paw of rats undergoing L5 spinal nerve transection (SNT) after the administration of control siRNA (CON group) or a cocktail of small interfering RNAs (siRNA) targeting TNF-α, IL-6 and IL1-β (COCK group). The data on the rats surviving for 6 d after SNT are expressed as mean ± SE. -1: 1 d prior to SNT, 0: the day of L5 SNT, 1, 2, 4 and 6: 1, 2, 4 and 6 d after L5 SNT. *P < 0.05 vs. CON group at each time point. MPE: maximal possible effect. The cut-off values for mechanical allodynia and hyperalgesia are 30 g and 250 g, respectively.
Mentions: The changes in mechanically induced allodynia and hyperalgesia in the rats surviving for 6 d after SNT are shown in Fig. 2. Allodynia and hyperalgesia were lower in the COCK group than in the CON group by 2 d after SNT (P < 0.05) and the difference was maintained for the duration of the experiment.

Bottom Line: Behavioral tests and levels of the cytokine mRNAs and proteins as well as glial cell activity were following the L5 SNT.In the behavioral tests, allodynia and hyperalgesia were significantly lower in the COCK group from 2 d after SNT (P < 0.05).RNA interference may be a method of reducing the development of mechanical allodynia and hyperalgesia in response to nerve injury.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

ABSTRACT

Background: The objective of this study was to investigate the time-course of the expression of TNF-α, IL-6, and IL-1β 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-α and IL-1β mRNA levels increased immediately after SNT and remained high for 6 d, while IL-6 transcripts only began to increase after 12 h. TNF-α and IL-1β 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-α, IL-6 and IL-1β 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.

No MeSH data available.


Related in: MedlinePlus