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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

Effects of AMG517, a TRPV1 antagonist, pretreatment on number of axons in the sciatic nerve 1 week after crush injury (toluidine blue staining).(A) Sciatic nerve cross-section at three sites around the injury. Proximal to the injury site, axons were sparsely distributed, with wide gaps between them. At the central injury site, there were also few axons, and mononuclear phagocytic cell infiltration and Schwann cell proliferation were visible. Distal to the injury site, marked myelin sheath disintegration and mononuclear phagocytic cell infiltration were observed. In rats pretreated with AMG517, Schwann cell proliferation and new myelin sheath formation were noted in particular at the central injury site, as well as proximal and distal to it. Scale bar: 20 μm; : Schwann cells; : mononuclear phagocytic cells; : new myelin sheath. (B) Significantly fewer axons were observed throughout the injury site (proximal, central, distal regions) and in both injury groups (treated, untreated) than in uninjured sciatic nerve; however, more axons were observed after AMG517 pretreatment. *P < 0.05, **P < 0.01, vs. uninjured side (mean ± SEM, n = 10; one-way analysis of variance and the least significant difference test); 1wk: 1 week; P: site proximal to injury; C: center of injury; D: site distal to injury; AMG: AMG517. I: Contralateral; II: 1 wk-P + vehicle; III: 1 wk-P-AMG; IV: 1 wk-C + vehicle; V: 1 wkc-AMG; VI: 1 wk-D + vehicle; VII: 1 wk-DAMG.
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Figure 3: Effects of AMG517, a TRPV1 antagonist, pretreatment on number of axons in the sciatic nerve 1 week after crush injury (toluidine blue staining).(A) Sciatic nerve cross-section at three sites around the injury. Proximal to the injury site, axons were sparsely distributed, with wide gaps between them. At the central injury site, there were also few axons, and mononuclear phagocytic cell infiltration and Schwann cell proliferation were visible. Distal to the injury site, marked myelin sheath disintegration and mononuclear phagocytic cell infiltration were observed. In rats pretreated with AMG517, Schwann cell proliferation and new myelin sheath formation were noted in particular at the central injury site, as well as proximal and distal to it. Scale bar: 20 μm; : Schwann cells; : mononuclear phagocytic cells; : new myelin sheath. (B) Significantly fewer axons were observed throughout the injury site (proximal, central, distal regions) and in both injury groups (treated, untreated) than in uninjured sciatic nerve; however, more axons were observed after AMG517 pretreatment. *P < 0.05, **P < 0.01, vs. uninjured side (mean ± SEM, n = 10; one-way analysis of variance and the least significant difference test); 1wk: 1 week; P: site proximal to injury; C: center of injury; D: site distal to injury; AMG: AMG517. I: Contralateral; II: 1 wk-P + vehicle; III: 1 wk-P-AMG; IV: 1 wk-C + vehicle; V: 1 wkc-AMG; VI: 1 wk-D + vehicle; VII: 1 wk-DAMG.

Mentions: Toluidine blue staining of semithin sciatic nerve sections revealed that, 1 week after injury, few axons and little myelin sheath remained at the injury site and in the region distal to it (Figure 3A). A large number of phagocytic cells had infiltrated into the region, and the number of cells at the center of the injury site was markedly elevated. Schwann cell nuclei were large, with distinct nucleoli. The histological characteristics of neurites were absent. Schwann cells had proliferated and surrounded regenerating axons in the tissue proximal to the injury site. Compared with the contralateral nerve, fewer neurites were observed across all three sites. In rats pretreated with AMG517, notable Schwann cell proliferation was seen, and the number of axons was elevated. There was no significant difference in axon number between the injury with vehicle and injury + AMG517 groups in any of the three regions (P > 0.05); however, a trend for AMG517 pretreatment to accelerate axon regeneration was observed (Figure 3B).


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)

Effects of AMG517, a TRPV1 antagonist, pretreatment on number of axons in the sciatic nerve 1 week after crush injury (toluidine blue staining).(A) Sciatic nerve cross-section at three sites around the injury. Proximal to the injury site, axons were sparsely distributed, with wide gaps between them. At the central injury site, there were also few axons, and mononuclear phagocytic cell infiltration and Schwann cell proliferation were visible. Distal to the injury site, marked myelin sheath disintegration and mononuclear phagocytic cell infiltration were observed. In rats pretreated with AMG517, Schwann cell proliferation and new myelin sheath formation were noted in particular at the central injury site, as well as proximal and distal to it. Scale bar: 20 μm; : Schwann cells; : mononuclear phagocytic cells; : new myelin sheath. (B) Significantly fewer axons were observed throughout the injury site (proximal, central, distal regions) and in both injury groups (treated, untreated) than in uninjured sciatic nerve; however, more axons were observed after AMG517 pretreatment. *P < 0.05, **P < 0.01, vs. uninjured side (mean ± SEM, n = 10; one-way analysis of variance and the least significant difference test); 1wk: 1 week; P: site proximal to injury; C: center of injury; D: site distal to injury; AMG: AMG517. I: Contralateral; II: 1 wk-P + vehicle; III: 1 wk-P-AMG; IV: 1 wk-C + vehicle; V: 1 wkc-AMG; VI: 1 wk-D + vehicle; VII: 1 wk-DAMG.
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Figure 3: Effects of AMG517, a TRPV1 antagonist, pretreatment on number of axons in the sciatic nerve 1 week after crush injury (toluidine blue staining).(A) Sciatic nerve cross-section at three sites around the injury. Proximal to the injury site, axons were sparsely distributed, with wide gaps between them. At the central injury site, there were also few axons, and mononuclear phagocytic cell infiltration and Schwann cell proliferation were visible. Distal to the injury site, marked myelin sheath disintegration and mononuclear phagocytic cell infiltration were observed. In rats pretreated with AMG517, Schwann cell proliferation and new myelin sheath formation were noted in particular at the central injury site, as well as proximal and distal to it. Scale bar: 20 μm; : Schwann cells; : mononuclear phagocytic cells; : new myelin sheath. (B) Significantly fewer axons were observed throughout the injury site (proximal, central, distal regions) and in both injury groups (treated, untreated) than in uninjured sciatic nerve; however, more axons were observed after AMG517 pretreatment. *P < 0.05, **P < 0.01, vs. uninjured side (mean ± SEM, n = 10; one-way analysis of variance and the least significant difference test); 1wk: 1 week; P: site proximal to injury; C: center of injury; D: site distal to injury; AMG: AMG517. I: Contralateral; II: 1 wk-P + vehicle; III: 1 wk-P-AMG; IV: 1 wk-C + vehicle; V: 1 wkc-AMG; VI: 1 wk-D + vehicle; VII: 1 wk-DAMG.
Mentions: Toluidine blue staining of semithin sciatic nerve sections revealed that, 1 week after injury, few axons and little myelin sheath remained at the injury site and in the region distal to it (Figure 3A). A large number of phagocytic cells had infiltrated into the region, and the number of cells at the center of the injury site was markedly elevated. Schwann cell nuclei were large, with distinct nucleoli. The histological characteristics of neurites were absent. Schwann cells had proliferated and surrounded regenerating axons in the tissue proximal to the injury site. Compared with the contralateral nerve, fewer neurites were observed across all three sites. In rats pretreated with AMG517, notable Schwann cell proliferation was seen, and the number of axons was elevated. There was no significant difference in axon number between the injury with vehicle and injury + AMG517 groups in any of the three regions (P > 0.05); however, a trend for AMG517 pretreatment to accelerate axon regeneration was observed (Figure 3B).

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