Research:Wnt blockade a possible Double Whammy

R
Yuan S et al. Wnt Signaling in the Pathogenesis of Multiple Sclerosis-Associated Chronic PainJ Neuroimmune Pharmacol. 2012 May 2. [Epub ahead of print]

Many multiple sclerosis
(MS) patients develop chronic pain, but the underlying pathological
mechanism is unknown. Mice with experimental autoimmune
encephalomyelitis (EAE) have been widely used to model MS-related
neurological complications, including CNS demyelination,
neuroinflammation and motor impairments. Similar to MS patients, EAE
mice also develop pain. We are interested in elucidating the
potential involvement of Wnt signaling in the pathogenesis of chronic
pain in EAE mice. In this study, we characterized the expression of Wnt
signaling proteins in the spinal cord dorsal horn (SCDH) of EAE mice, by
immunoblotting and immunostaining.




The EAE model was created by
immunization of adult mice (C57BL/6, 10 weeks) with myelin
oligodendrocyte glycoprotein (MOG) 35-55. Robust mechanical hyperalgesia
(a painful sensation sucha nipping a toe, becomes more painful) and allodynia (a non painful stimulus becomes painful) were developed in both fore- and hindpaws of the EAE
mice. 



In my opinion this is not the same as neuropathic pain, pain generated by the action of the nerves, as occurs in MS and probably responds to a differnt set of drugs.


Wnt3a, a prototypical Wnt ligand for the canonical pathway, was
significantly increased in the SCDH of the EAE mice. Another key protein
in the canonical pathway, ß-catenin, was also significantly
up-regulated. In addition, Wnt5a, a prototypic Wnt ligand for the
non-canonical pathway, and its receptor (co-receptor) Ror2 were also
up-regulated in the SCDH of the EAE mice. We further found that Wnt5a
antagonist Box5 and β-catenin inhibitor indomethacin (actually it is better known as a prostaglandin inhibitor) attenuated
mechanical allodynia in the EAE mice. Our data collectively suggest that
Wnt signaling pathways are up-regulated in the SCDH of the EAE mice and
that aberrant activation of Wnt signaling contributes to the
development of EAE-related pain.




The Wnt (named after a gene that resulted in wingless fruitflies) signaling pathway is a network of protein that are involved in development of the embryo (embryogenesis ), The study here suggests that it may be involved in the developmnet of some aspects of altered sensation or pain. Whilst this may have some significance to MS,the reason I have highlighted this research paper is because of another interest in Wnt pathway is in myelination. It has been suggested that Wnt-beta-catenin signaling in oligodendrocyte precurosir cells can result in a profound delay of both developmental myelination and
remyelination. Therefore the stimulating wnt such as wnt3a is blocking repair via preventing immature oligodendrocytes from maturing into myelinating oligodendrocytes as shown in previous studies and the blocking of Wnt function may facilitate remyelination. Therefore as blocking Wnt may also have some beneficial effect on inhibiting pain responses, this target may give us a double Whammy to also stimulate remyelination. As ever this is just theorectical and proff in MS is lacking, but this data suggests a way to offer benefit in MS.

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