Abstract
Spinal glial cells contribute to the development of many types of inflammatory and
neuropathic pain. Here the contribution of spinal astrocytes and astrocyte gap junctions
to oxaliplatin-induced mechanical hypersensitivity was explored. The expression of
glial fibrillary acidic protein (GFAP) in spinal dorsal horn was significantly increased
at day 7 but recovered at day 14 after oxaliplatin treatment, suggesting a transient
activation of spinal astrocytes by chemotherapy. Astrocyte-specific gap junction protein
connexin 43 (Cx43) was significantly increased in dorsal horn at both day 7 and day
14 following chemotherapy, but neuronal (connexin 36 [Cx36]) and oligodendrocyte (connexin
32 [Cx32]) gap junction proteins did not show any change. Blockade of astrocyte gap
junction with carbenoxolone (CBX) prevented oxaliplatin-induced mechanical hypersensitivity
in a dose-dependent manner and the increase of spinal GFAP expression, but had no
effect once the mechanical hypersensitivity induced by oxaliplatin had fully developed.
These results suggest that oxaliplatin chemotherapy induces the activation of spinal
astrocytes and this is accompanied by increased expression of astrocyte-astrocyte
gap junction connections via Cx43. These alterations in spinal astrocytes appear to
contribute to the induction but not the maintenance of oxaliplatin-induced mechanical
hypersensitivity. Combined, these results suggest that targeting spinal astrocyte/astrocyte-specific
gap junction could be a new therapeutic strategy to prevent oxaliplatin-induced neuropathy.
Perspective
Spinal astrocytes but not microglia were recently shown to be recruited in paclitaxel-related
chemoneuropathy. Here, spinal astrocyte gap junctions are shown to play an important
role in the induction of oxaliplatin neuropathy.
Key words
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Article info
Publication history
Accepted:
November 7,
2012
Received in revised form:
October 29,
2012
Received:
August 23,
2012
Footnotes
This work was supported by National Institutes of Health grant NS46606 and National Cancer Institute grant CA124787.
The authors declare no conflicts of interest.
Identification
Copyright
© 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.
