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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

Immunofluorescence staining for TRPV1 in the L4 dorsal root ganglion following sciatic nerve crush injury.Some small TRPV1-positive neurons were visible in the uninjured nerve. At 1 and 2 weeks after injury + vehicle, the number of TRPV1-positive neurons in L4 dorsal root ganglion (green fluorescence) was greater in the injured side than the control side. Moreover, some large-diameter neurons showed positive immunofluorescence. Fewer TRPV1-positive neurons were observed in AMG517 (TRPV1 antagonist)-pretreated groups than in the non-pretreated injury groups. Blue fluorescence (4′,6-diamidino-2-phenylindole, DAPI), nuclei. TRPV1: Transient receptor potential cation channel subfamily V member 1; AMG: AMG517. Scale bar: 50 μm.
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Figure 8: Immunofluorescence staining for TRPV1 in the L4 dorsal root ganglion following sciatic nerve crush injury.Some small TRPV1-positive neurons were visible in the uninjured nerve. At 1 and 2 weeks after injury + vehicle, the number of TRPV1-positive neurons in L4 dorsal root ganglion (green fluorescence) was greater in the injured side than the control side. Moreover, some large-diameter neurons showed positive immunofluorescence. Fewer TRPV1-positive neurons were observed in AMG517 (TRPV1 antagonist)-pretreated groups than in the non-pretreated injury groups. Blue fluorescence (4′,6-diamidino-2-phenylindole, DAPI), nuclei. TRPV1: Transient receptor potential cation channel subfamily V member 1; AMG: AMG517. Scale bar: 50 μm.

Mentions: On the ipsilateral side, 1 and 2 weeks after injury, the number of TRPV1-positive cells in L4 DRGs was noticeably greater than on the contralateral side. Moreover, TRPV1-positive cells were large, medium-sized and small (Figure 8). Following AMG517 pretreatment, there were fewer TRPV1-positive cells on the injured side than the uninjured side (P < 0.05). No significant difference was observed in the percentage of TRPV1-positive neurons between the AMG 517-pretreated and vehicle-pretreated groups (P > 0.05; Table 2).


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)

Immunofluorescence staining for TRPV1 in the L4 dorsal root ganglion following sciatic nerve crush injury.Some small TRPV1-positive neurons were visible in the uninjured nerve. At 1 and 2 weeks after injury + vehicle, the number of TRPV1-positive neurons in L4 dorsal root ganglion (green fluorescence) was greater in the injured side than the control side. Moreover, some large-diameter neurons showed positive immunofluorescence. Fewer TRPV1-positive neurons were observed in AMG517 (TRPV1 antagonist)-pretreated groups than in the non-pretreated injury groups. Blue fluorescence (4′,6-diamidino-2-phenylindole, DAPI), nuclei. TRPV1: Transient receptor potential cation channel subfamily V member 1; AMG: AMG517. Scale bar: 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590249&req=5

Figure 8: Immunofluorescence staining for TRPV1 in the L4 dorsal root ganglion following sciatic nerve crush injury.Some small TRPV1-positive neurons were visible in the uninjured nerve. At 1 and 2 weeks after injury + vehicle, the number of TRPV1-positive neurons in L4 dorsal root ganglion (green fluorescence) was greater in the injured side than the control side. Moreover, some large-diameter neurons showed positive immunofluorescence. Fewer TRPV1-positive neurons were observed in AMG517 (TRPV1 antagonist)-pretreated groups than in the non-pretreated injury groups. Blue fluorescence (4′,6-diamidino-2-phenylindole, DAPI), nuclei. TRPV1: Transient receptor potential cation channel subfamily V member 1; AMG: AMG517. Scale bar: 50 μm.
Mentions: On the ipsilateral side, 1 and 2 weeks after injury, the number of TRPV1-positive cells in L4 DRGs was noticeably greater than on the contralateral side. Moreover, TRPV1-positive cells were large, medium-sized and small (Figure 8). Following AMG517 pretreatment, there were fewer TRPV1-positive cells on the injured side than the uninjured side (P < 0.05). No significant difference was observed in the percentage of TRPV1-positive neurons between the AMG 517-pretreated and vehicle-pretreated groups (P > 0.05; Table 2).

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