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Targeting anti-inflammatory treatment can ameliorate injury-induced neuropathic pain.

Iwatsuki K, Arai T, Ota H, Kato S, Natsume T, Kurimoto S, Yamamoto M, Hirata H - PLoS ONE (2013)

Bottom Line: Etanercept treatment improved recovery of motor nerve conduction velocity, muscle weight loss, and sciatic functional index.Etanercept reduced expression of interleukin-6 and monocyte chemotactic and activating factor-1 at the crushed sciatic nerve.Etanercept does not impede the onset or progression of Wallerian degeneration, but optimizes the involvement of macrophages and the secretion of inflammatory mediators.

View Article: PubMed Central - PubMed

Affiliation: Department of Hand Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan. kiwatsuki@med.nagoya-u.ac.jp

ABSTRACT
Tumor necrosis factor-α plays important roles in immune system development, immune response regulation, and T-cell-mediated tissue injury. The present study assessed the net value of anti-tumor necrosis factor-α treatment in terms of functional recovery and inhibition of hypersensitivity after peripheral nerve crush injury. We created a right sciatic nerve crush injury model using a Sugita aneurysm clip. Animals were separated into 3 groups: the first group received only a skin incision; the second group received nerve crush injury and intraperitoneal vehicle injection; and the third group received nerve crush injury and intraperitoneal etanercept (6 mg/kg). Etanercept treatment improved recovery of motor nerve conduction velocity, muscle weight loss, and sciatic functional index. Plantar thermal and von Frey mechanical withdrawal thresholds recovered faster in the etanercept group than in the control group. On day 7 after crush injury, the numbers of ED-1-positive cells in crushed nerves of the control and etanercept groups were increased compared to that in the sham-treated group. After 21 days, ED-1-positive cells had nearly disappeared from the etanercept group. Etanercept reduced expression of interleukin-6 and monocyte chemotactic and activating factor-1 at the crushed sciatic nerve. These findings demonstrate the utility of etanercept, in terms of both enhancing functional recovery and suppressing hypersensitivity after nerve crush. Etanercept does not impede the onset or progression of Wallerian degeneration, but optimizes the involvement of macrophages and the secretion of inflammatory mediators.

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Effect of etanercept on mRNA expressions.The baseline was drawn at a value of 1 (average for the sham group) (**p<0.01; *p<0.05; ‡p<0.01; †p<0.05, compared to sham group). A) Expressions of TNF-α mRNA at the crushed nerve. B) Expression of IL-6 mRNA at the crushed nerve. C) Expression of MCP-1 mRNA at the crushed nerve. D) Expression of IL-1 mRNA at the crushed nerve. E) Expression of P2RX7 mRNA at the crushed nerve. F) Expression of Nav1.3 mRNA at the L5 DRG. G) Expression of Nav1.8 mRNA at the L5 DRG. H) Expression of Nav1.9 mRNA at the L5 DRG.
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pone-0057721-g005: Effect of etanercept on mRNA expressions.The baseline was drawn at a value of 1 (average for the sham group) (**p<0.01; *p<0.05; ‡p<0.01; †p<0.05, compared to sham group). A) Expressions of TNF-α mRNA at the crushed nerve. B) Expression of IL-6 mRNA at the crushed nerve. C) Expression of MCP-1 mRNA at the crushed nerve. D) Expression of IL-1 mRNA at the crushed nerve. E) Expression of P2RX7 mRNA at the crushed nerve. F) Expression of Nav1.3 mRNA at the L5 DRG. G) Expression of Nav1.8 mRNA at the L5 DRG. H) Expression of Nav1.9 mRNA at the L5 DRG.

Mentions: The mRNA levels of TNF-α and IL-6 after crush injury were determined by real-time polymerase chain reaction. Expression of TNF-α mRNA in the control and etanercept groups was increased on day 2, but the difference between the 2 groups was not significant, and expression returned to baseline levels by day 7 (Fig. 5A). Expressions of IL-6 mRNA were significantly higher in the control and etanercept groups and remained elevated over 35 days, but etanercept treatment reduced expression of IL-6 mRNA compared to the control group on day 7 (Fig. 5B). Expression of MCP-1 mRNA was significantly higher in the control and etanercept groups on day 2, but etanercept treatment reduced expression of MCP-1 mRNA on days 7 (Fig. 5C). Expression of IL-1β mRNA was upregulated on day 7 after nerve crush, but no significant differences between the control and etanercept groups were identified (Fig. 5D). Expression of P2RX7 mRNA was upregulated after crush injury, and etanercept reduced the P2RX7 expression (Fig. 5E). Crush injury appeared to change the types of sodium channel expressed at the DRG, and etanercept reduced these changes (Fig. 5F–H).


Targeting anti-inflammatory treatment can ameliorate injury-induced neuropathic pain.

Iwatsuki K, Arai T, Ota H, Kato S, Natsume T, Kurimoto S, Yamamoto M, Hirata H - PLoS ONE (2013)

Effect of etanercept on mRNA expressions.The baseline was drawn at a value of 1 (average for the sham group) (**p<0.01; *p<0.05; ‡p<0.01; †p<0.05, compared to sham group). A) Expressions of TNF-α mRNA at the crushed nerve. B) Expression of IL-6 mRNA at the crushed nerve. C) Expression of MCP-1 mRNA at the crushed nerve. D) Expression of IL-1 mRNA at the crushed nerve. E) Expression of P2RX7 mRNA at the crushed nerve. F) Expression of Nav1.3 mRNA at the L5 DRG. G) Expression of Nav1.8 mRNA at the L5 DRG. H) Expression of Nav1.9 mRNA at the L5 DRG.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3585184&req=5

pone-0057721-g005: Effect of etanercept on mRNA expressions.The baseline was drawn at a value of 1 (average for the sham group) (**p<0.01; *p<0.05; ‡p<0.01; †p<0.05, compared to sham group). A) Expressions of TNF-α mRNA at the crushed nerve. B) Expression of IL-6 mRNA at the crushed nerve. C) Expression of MCP-1 mRNA at the crushed nerve. D) Expression of IL-1 mRNA at the crushed nerve. E) Expression of P2RX7 mRNA at the crushed nerve. F) Expression of Nav1.3 mRNA at the L5 DRG. G) Expression of Nav1.8 mRNA at the L5 DRG. H) Expression of Nav1.9 mRNA at the L5 DRG.
Mentions: The mRNA levels of TNF-α and IL-6 after crush injury were determined by real-time polymerase chain reaction. Expression of TNF-α mRNA in the control and etanercept groups was increased on day 2, but the difference between the 2 groups was not significant, and expression returned to baseline levels by day 7 (Fig. 5A). Expressions of IL-6 mRNA were significantly higher in the control and etanercept groups and remained elevated over 35 days, but etanercept treatment reduced expression of IL-6 mRNA compared to the control group on day 7 (Fig. 5B). Expression of MCP-1 mRNA was significantly higher in the control and etanercept groups on day 2, but etanercept treatment reduced expression of MCP-1 mRNA on days 7 (Fig. 5C). Expression of IL-1β mRNA was upregulated on day 7 after nerve crush, but no significant differences between the control and etanercept groups were identified (Fig. 5D). Expression of P2RX7 mRNA was upregulated after crush injury, and etanercept reduced the P2RX7 expression (Fig. 5E). Crush injury appeared to change the types of sodium channel expressed at the DRG, and etanercept reduced these changes (Fig. 5F–H).

Bottom Line: Etanercept treatment improved recovery of motor nerve conduction velocity, muscle weight loss, and sciatic functional index.Etanercept reduced expression of interleukin-6 and monocyte chemotactic and activating factor-1 at the crushed sciatic nerve.Etanercept does not impede the onset or progression of Wallerian degeneration, but optimizes the involvement of macrophages and the secretion of inflammatory mediators.

View Article: PubMed Central - PubMed

Affiliation: Department of Hand Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan. kiwatsuki@med.nagoya-u.ac.jp

ABSTRACT
Tumor necrosis factor-α plays important roles in immune system development, immune response regulation, and T-cell-mediated tissue injury. The present study assessed the net value of anti-tumor necrosis factor-α treatment in terms of functional recovery and inhibition of hypersensitivity after peripheral nerve crush injury. We created a right sciatic nerve crush injury model using a Sugita aneurysm clip. Animals were separated into 3 groups: the first group received only a skin incision; the second group received nerve crush injury and intraperitoneal vehicle injection; and the third group received nerve crush injury and intraperitoneal etanercept (6 mg/kg). Etanercept treatment improved recovery of motor nerve conduction velocity, muscle weight loss, and sciatic functional index. Plantar thermal and von Frey mechanical withdrawal thresholds recovered faster in the etanercept group than in the control group. On day 7 after crush injury, the numbers of ED-1-positive cells in crushed nerves of the control and etanercept groups were increased compared to that in the sham-treated group. After 21 days, ED-1-positive cells had nearly disappeared from the etanercept group. Etanercept reduced expression of interleukin-6 and monocyte chemotactic and activating factor-1 at the crushed sciatic nerve. These findings demonstrate the utility of etanercept, in terms of both enhancing functional recovery and suppressing hypersensitivity after nerve crush. Etanercept does not impede the onset or progression of Wallerian degeneration, but optimizes the involvement of macrophages and the secretion of inflammatory mediators.

Show MeSH
Related in: MedlinePlus