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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

mRNA expression of TNF-α, IL-6, and IL-1β in rats undergoing L5 spinal nerve transection (SNT) after the administration of the cocktail of small interfering RNA (siRNA) targeting TNF-α, IL-6 and IL-1β (COCK group). See legend to Fig. 3 for further details. The mRNA levels for TNF-α, IL-6 and IL-1β at 4 h after SNT are not determined because of a technical error which occurred during the analysis process.
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Figure 4: mRNA expression of TNF-α, IL-6, and IL-1β in rats undergoing L5 spinal nerve transection (SNT) after the administration of the cocktail of small interfering RNA (siRNA) targeting TNF-α, IL-6 and IL-1β (COCK group). See legend to Fig. 3 for further details. The mRNA levels for TNF-α, IL-6 and IL-1β at 4 h after SNT are not determined because of a technical error which occurred during the analysis process.

Mentions: The levels of expression of TNF-α, IL-6, and IL-1β transcripts in the CON and COCK groups are depicted in Figs. 3 and 4, respectively, and the time-course of expression in both groups is shown in Fig. 5. TNF-α level in the CON group increased rapidly after SNT, reaching a maximum (approximately 4.1 fold) at 12 h, and remained high for 6 d (maximum increase ~6.4 fold). IL-6 mRNA in the CON group increased by 12 h after SNT and continued to rise over the 6 d, with considerable variability at 6 d after SNT. A similar increase was observed for IL-1β mRNAs in the CON group. TNF-α and IL-1β mRNA levels at all time points were lower in the COCK group than the CON group (P < 0.05), and the levels of IL-6 mRNA levels at 12 h, 1 and 2 d after L5 SNT in the COCK group were lower than in the CON group (P < 0.05). Overall the administration of siRNA resulted in ~42-64% inhibition of the expression of the proinflammatory cytokines over 6 days.


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)

mRNA expression of TNF-α, IL-6, and IL-1β in rats undergoing L5 spinal nerve transection (SNT) after the administration of the cocktail of small interfering RNA (siRNA) targeting TNF-α, IL-6 and IL-1β (COCK group). See legend to Fig. 3 for further details. The mRNA levels for TNF-α, IL-6 and IL-1β at 4 h after SNT are not determined because of a technical error which occurred during the analysis process.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: mRNA expression of TNF-α, IL-6, and IL-1β in rats undergoing L5 spinal nerve transection (SNT) after the administration of the cocktail of small interfering RNA (siRNA) targeting TNF-α, IL-6 and IL-1β (COCK group). See legend to Fig. 3 for further details. The mRNA levels for TNF-α, IL-6 and IL-1β at 4 h after SNT are not determined because of a technical error which occurred during the analysis process.
Mentions: The levels of expression of TNF-α, IL-6, and IL-1β transcripts in the CON and COCK groups are depicted in Figs. 3 and 4, respectively, and the time-course of expression in both groups is shown in Fig. 5. TNF-α level in the CON group increased rapidly after SNT, reaching a maximum (approximately 4.1 fold) at 12 h, and remained high for 6 d (maximum increase ~6.4 fold). IL-6 mRNA in the CON group increased by 12 h after SNT and continued to rise over the 6 d, with considerable variability at 6 d after SNT. A similar increase was observed for IL-1β mRNAs in the CON group. TNF-α and IL-1β mRNA levels at all time points were lower in the COCK group than the CON group (P < 0.05), and the levels of IL-6 mRNA levels at 12 h, 1 and 2 d after L5 SNT in the COCK group were lower than in the CON group (P < 0.05). Overall the administration of siRNA resulted in ~42-64% inhibition of the expression of the proinflammatory cytokines over 6 days.

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