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Blockade of transient receptor potential cation channel subfamily V member 1 promotes regeneration after sciatic nerve injury.

Ren F, Zhang H, Qi C, Gao ML, Wang H, Li XQ - Neural Regen Res (2015)

Bottom Line: TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side.Pretreatment with AMG517 blocked this effect.These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi Province, China.

ABSTRACT
The transient receptor potential cation channel subfamily V member 1 (TRPV1) provides the sensation of pain (nociception). However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517 (300 mg/kg), a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immunofluorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clusters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve.

No MeSH data available.


Related in: MedlinePlus

Number of axons in sciatic nerve transverse section 1 and 2 weeks after crush injury, with or without AMG517, a TRPV1 antagonist, pretreatment.**P < 0.01, 1 vs. 2 weeks, with AMG517 pretreatment; ***P < 0.001, central vs. distal injury site (one-way analysis of variance and the least significant difference test). Data are expressed as the mean ± SD; n = 10. AMG: AMG517.
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Figure 5: Number of axons in sciatic nerve transverse section 1 and 2 weeks after crush injury, with or without AMG517, a TRPV1 antagonist, pretreatment.**P < 0.01, 1 vs. 2 weeks, with AMG517 pretreatment; ***P < 0.001, central vs. distal injury site (one-way analysis of variance and the least significant difference test). Data are expressed as the mean ± SD; n = 10. AMG: AMG517.

Mentions: Two weeks after injury, regeneration was evident. Compared with the contralateral side, the number of axons was notably elevated in the region proximal to the injury site, and the number of cells was also greater in the center of the injury site and distal to it. Numerous new myelinated axons surrounded by Schwann cells were visible. These changes, indicative of regeneration, were particularly prominent in rats pretreated with AMG517, at the proximal to the injury site, more neurites were observed than in control nerves; there were more fine, focal, unmyelinated nerve clusters (aggregates of more than five unmyelinated fibers) in the AMG517-pretreated injured nerves than in contralateral or vehicle-pretreated injured nerves (P < 0.001), exceeding 10 fibers in most clusters (Figure 4). Schwann cells proliferated noticeably at, and distal to, the injury site. Single or multiple new myelin sheaths with thin walls were found in Schwann cells. There were fewer phagocytic cells within foci in the AMG 517-pretreated injury groups than the vehicle-pretreated injury groups, but phagocytosis was still evident (Figure 4). Furthermore, in the AMG517-pretreated group, the total number of axons was greater 2 weeks after injury than at 1 week with vehicle-pretreatment (P < 0.01; Figure 5).


Blockade of transient receptor potential cation channel subfamily V member 1 promotes regeneration after sciatic nerve injury.

Ren F, Zhang H, Qi C, Gao ML, Wang H, Li XQ - Neural Regen Res (2015)

Number of axons in sciatic nerve transverse section 1 and 2 weeks after crush injury, with or without AMG517, a TRPV1 antagonist, pretreatment.**P < 0.01, 1 vs. 2 weeks, with AMG517 pretreatment; ***P < 0.001, central vs. distal injury site (one-way analysis of variance and the least significant difference test). Data are expressed as the mean ± SD; n = 10. AMG: AMG517.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 5: Number of axons in sciatic nerve transverse section 1 and 2 weeks after crush injury, with or without AMG517, a TRPV1 antagonist, pretreatment.**P < 0.01, 1 vs. 2 weeks, with AMG517 pretreatment; ***P < 0.001, central vs. distal injury site (one-way analysis of variance and the least significant difference test). Data are expressed as the mean ± SD; n = 10. AMG: AMG517.
Mentions: Two weeks after injury, regeneration was evident. Compared with the contralateral side, the number of axons was notably elevated in the region proximal to the injury site, and the number of cells was also greater in the center of the injury site and distal to it. Numerous new myelinated axons surrounded by Schwann cells were visible. These changes, indicative of regeneration, were particularly prominent in rats pretreated with AMG517, at the proximal to the injury site, more neurites were observed than in control nerves; there were more fine, focal, unmyelinated nerve clusters (aggregates of more than five unmyelinated fibers) in the AMG517-pretreated injured nerves than in contralateral or vehicle-pretreated injured nerves (P < 0.001), exceeding 10 fibers in most clusters (Figure 4). Schwann cells proliferated noticeably at, and distal to, the injury site. Single or multiple new myelin sheaths with thin walls were found in Schwann cells. There were fewer phagocytic cells within foci in the AMG 517-pretreated injury groups than the vehicle-pretreated injury groups, but phagocytosis was still evident (Figure 4). Furthermore, in the AMG517-pretreated group, the total number of axons was greater 2 weeks after injury than at 1 week with vehicle-pretreatment (P < 0.01; Figure 5).

Bottom Line: TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side.Pretreatment with AMG517 blocked this effect.These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi Province, China.

ABSTRACT
The transient receptor potential cation channel subfamily V member 1 (TRPV1) provides the sensation of pain (nociception). However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517 (300 mg/kg), a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immunofluorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clusters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve.

No MeSH data available.


Related in: MedlinePlus