Regulation of Wnt signaling by nociceptive input in animal models.
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.


CONCLUSIONS
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.
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Yuqiang
Y
Shi
Subo
S
Yuan
Bei
B
Li
Jigong
J
Wang
Susan M
SM
Carlton
Kyungsoon
K
Chung
Jin Mo
JM
Chung
Shao-Jun
SJ
Tang
D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000378:metabolism / Q000473:pathology; D059225:Nociception; D020671:Posterior Horn Cells / Q000378:metabolism / Q000473:pathology; D021381:Protein Transport; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D000071818:Wnt-5a Protein; D060509:Wnt3A Protein / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D015699:HIV Envelope Protein gp120; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; C438615:Wnt5a protein, mouse; D051176:beta Catenin; D002211:Capsaicin