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Regulation of Wnt signaling by nociceptive input in animal models.

Shi Y, Yuan S, Li B, Wang J, Carlton SM, Chung K, Chung JM, Tang SJ - Mol Pain (2012)

Bottom Line: In addition, Wnt3a, a prototypic Wnt ligand that activates the canonical pathway, is also enriched in the superficial layers.Furthermore, Wnt5a, a prototypic Wnt ligand for non-canonical pathways, and its receptor Ror2 are also up-regulated in the SCDH of these models.Our results suggest that Wnt signaling pathways are regulated by nociceptive input.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.

ABSTRACT

Background: Central sensitization-associated synaptic plasticity in the spinal cord dorsal horn (SCDH) critically contributes to the development of chronic pain, but understanding of the underlying molecular pathways is still incomplete. Emerging evidence suggests that Wnt signaling plays a crucial role in regulation of synaptic plasticity. Little is known about the potential function of the Wnt signaling cascades in chronic pain development.

Results: Fluorescent immunostaining results indicate that β-catenin, an essential protein in the canonical Wnt signaling pathway, is expressed in the superficial layers of the mouse SCDH with enrichment at synapses in lamina II. In addition, Wnt3a, a prototypic Wnt ligand that activates the canonical pathway, is also enriched in the superficial layers. Immunoblotting analysis indicates that both Wnt3a a β-catenin are up-regulated in the SCDH of various mouse pain models created by hind-paw injection of capsaicin, intrathecal (i.t.) injection of HIV-gp120 protein or spinal nerve ligation (SNL). Furthermore, Wnt5a, a prototypic Wnt ligand for non-canonical pathways, and its receptor Ror2 are also up-regulated in the SCDH of these models.

Conclusion: Our results suggest that Wnt signaling pathways are regulated by nociceptive input. The activation of Wnt signaling may regulate the expression of spinal central sensitization during the development of acute and chronic pain.

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Expression profiles of Wnt signaling proteins in the HIV-gp120 pain model.A. Time course of mechanical allodynia induced by intrathecal (i.t.) HIV-gp120 injection (vehicle controls: saline injection). Following gp120 administration, mice developed mechanical hypersensitivity. B-D. Protein levels of Wnt3a (B), ABC (C), and TBC (D) at different time points after HIV-gp120 injection. The proteins were gradually up-regulated after the injection. E-F. Expression of Wnt5a (E) and Ror2 (F) proteins at different time points after gp120 injection. Wnt5a rapidly increased, peaked at 15–30 min after injection, and returned to baseline by 2 h. Ror2 was also up-regulated and persisted at a high level at 3 h after injection. Data from at least three independent experiments are summarized in graphs at right (*, p < 0.05; one-way ANOVA).
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Figure 7: Expression profiles of Wnt signaling proteins in the HIV-gp120 pain model.A. Time course of mechanical allodynia induced by intrathecal (i.t.) HIV-gp120 injection (vehicle controls: saline injection). Following gp120 administration, mice developed mechanical hypersensitivity. B-D. Protein levels of Wnt3a (B), ABC (C), and TBC (D) at different time points after HIV-gp120 injection. The proteins were gradually up-regulated after the injection. E-F. Expression of Wnt5a (E) and Ror2 (F) proteins at different time points after gp120 injection. Wnt5a rapidly increased, peaked at 15–30 min after injection, and returned to baseline by 2 h. Ror2 was also up-regulated and persisted at a high level at 3 h after injection. Data from at least three independent experiments are summarized in graphs at right (*, p < 0.05; one-way ANOVA).

Mentions: We next determined the regulated expression of Wnt proteins in the HIV gp120 pain model. Previous work established that intrathecal injection (i.t.) of HIV-gp120 protein induces hyperalgesia and mechanical allodynia in animals [56-59]. Indeed, following gp120 administration, mice showed a progressive decrease in PWT evoked by von Frey filaments (Figure 7 A). The mechanical allodynia was observed at 1 h after gp120 injection, and fully developed by 2–5 h. Immunoblotting results showed that Wnt3a, ABC and TBC progressively increased in the SCDH during the development of allodynia (Figure 7 B-D). The protein levels started increasing within 1 h after gp120 injection and peaked at 2–3 h (Figure 7 B-D). Although the magnitudes of the peak increases differed among Wnt3a (1.4 fold, p < 0.05), ABC (2.2 fold, p < 0.05) and TBC (1.9 fold, p < 0.05), the proteins displayed similar temporal profiles of up-regulation. The progressive up-regulation of the proteins seemed to be parallel to the temporal profile of allodynic expression (Figure 7 A).


Regulation of Wnt signaling by nociceptive input in animal models.

Shi Y, Yuan S, Li B, Wang J, Carlton SM, Chung K, Chung JM, Tang SJ - Mol Pain (2012)

Expression profiles of Wnt signaling proteins in the HIV-gp120 pain model.A. Time course of mechanical allodynia induced by intrathecal (i.t.) HIV-gp120 injection (vehicle controls: saline injection). Following gp120 administration, mice developed mechanical hypersensitivity. B-D. Protein levels of Wnt3a (B), ABC (C), and TBC (D) at different time points after HIV-gp120 injection. The proteins were gradually up-regulated after the injection. E-F. Expression of Wnt5a (E) and Ror2 (F) proteins at different time points after gp120 injection. Wnt5a rapidly increased, peaked at 15–30 min after injection, and returned to baseline by 2 h. Ror2 was also up-regulated and persisted at a high level at 3 h after injection. Data from at least three independent experiments are summarized in graphs at right (*, p < 0.05; one-way ANOVA).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 7: Expression profiles of Wnt signaling proteins in the HIV-gp120 pain model.A. Time course of mechanical allodynia induced by intrathecal (i.t.) HIV-gp120 injection (vehicle controls: saline injection). Following gp120 administration, mice developed mechanical hypersensitivity. B-D. Protein levels of Wnt3a (B), ABC (C), and TBC (D) at different time points after HIV-gp120 injection. The proteins were gradually up-regulated after the injection. E-F. Expression of Wnt5a (E) and Ror2 (F) proteins at different time points after gp120 injection. Wnt5a rapidly increased, peaked at 15–30 min after injection, and returned to baseline by 2 h. Ror2 was also up-regulated and persisted at a high level at 3 h after injection. Data from at least three independent experiments are summarized in graphs at right (*, p < 0.05; one-way ANOVA).
Mentions: We next determined the regulated expression of Wnt proteins in the HIV gp120 pain model. Previous work established that intrathecal injection (i.t.) of HIV-gp120 protein induces hyperalgesia and mechanical allodynia in animals [56-59]. Indeed, following gp120 administration, mice showed a progressive decrease in PWT evoked by von Frey filaments (Figure 7 A). The mechanical allodynia was observed at 1 h after gp120 injection, and fully developed by 2–5 h. Immunoblotting results showed that Wnt3a, ABC and TBC progressively increased in the SCDH during the development of allodynia (Figure 7 B-D). The protein levels started increasing within 1 h after gp120 injection and peaked at 2–3 h (Figure 7 B-D). Although the magnitudes of the peak increases differed among Wnt3a (1.4 fold, p < 0.05), ABC (2.2 fold, p < 0.05) and TBC (1.9 fold, p < 0.05), the proteins displayed similar temporal profiles of up-regulation. The progressive up-regulation of the proteins seemed to be parallel to the temporal profile of allodynic expression (Figure 7 A).

Bottom Line: In addition, Wnt3a, a prototypic Wnt ligand that activates the canonical pathway, is also enriched in the superficial layers.Furthermore, Wnt5a, a prototypic Wnt ligand for non-canonical pathways, and its receptor Ror2 are also up-regulated in the SCDH of these models.Our results suggest that Wnt signaling pathways are regulated by nociceptive input.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.

ABSTRACT

Background: Central sensitization-associated synaptic plasticity in the spinal cord dorsal horn (SCDH) critically contributes to the development of chronic pain, but understanding of the underlying molecular pathways is still incomplete. Emerging evidence suggests that Wnt signaling plays a crucial role in regulation of synaptic plasticity. Little is known about the potential function of the Wnt signaling cascades in chronic pain development.

Results: Fluorescent immunostaining results indicate that β-catenin, an essential protein in the canonical Wnt signaling pathway, is expressed in the superficial layers of the mouse SCDH with enrichment at synapses in lamina II. In addition, Wnt3a, a prototypic Wnt ligand that activates the canonical pathway, is also enriched in the superficial layers. Immunoblotting analysis indicates that both Wnt3a a β-catenin are up-regulated in the SCDH of various mouse pain models created by hind-paw injection of capsaicin, intrathecal (i.t.) injection of HIV-gp120 protein or spinal nerve ligation (SNL). Furthermore, Wnt5a, a prototypic Wnt ligand for non-canonical pathways, and its receptor Ror2 are also up-regulated in the SCDH of these models.

Conclusion: Our results suggest that Wnt signaling pathways are regulated by nociceptive input. The activation of Wnt signaling may regulate the expression of spinal central sensitization during the development of acute and chronic pain.

Show MeSH
Related in: MedlinePlus