Highlights
- •Integrin β1 transduces signals from extracellular matrix in a model of chronic pain.
- •Membrane lipid rafts also contribute to mechanisms of hyperalgesia in a model of chronic pain.
- •Our findings help define plasma membrane mechanisms in a preclinical model of chronic pain.
Abstract
We have recently shown that the prolongation of prostaglandin E2 hyperalgesia in a preclinical model of chronic pain—hyperalgesic priming—is mediated
by release of cyclic adenosine monophosphate from isolectin B4–positive nociceptors
and its metabolism by ectonucleotidases to produce adenosine. The adenosine, in turn,
acts in an autocrine mechanism at an A1 adenosine receptor whose downstream signaling
mechanisms in the nociceptor are altered to produce nociceptor sensitization. We previously
showed that antisense against an extracellular matrix molecule, versican, which defines
the population of nociceptors involved in hyperalgesic priming, eliminated the prolongation
of prostaglandin E2 hyperalgesia. To further evaluate the mechanisms at the interface between the extracellular
matrix and the nociceptor's plasma membrane involved in hyperalgesia prolongation,
we interrupted a plasma membrane molecule involved in versican signaling, integrin
β1, with an antisense oligodeoxynucleotide. Integrin β1 antisense eliminated mechanical
hyperalgesia induced by an adenosine A1 receptor agonist, cyclopentyladenosine, in
the primed rat. We also disrupted a molecular complex of signaling molecules that
contains integrin β1, lipid rafts, with methyl-β-cyclodextrin, which attenuated the
prolongation without affecting the acute phase of prostaglandin E2 hyperalgesia, while having no effect on cyclopentyladenosine hyperalgesia. Our findings
help to define the plasma membrane mechanisms involved in a preclinical model of chronic
pain.
Perspective
The present study contributes to a further understanding of mechanisms involved in
the organization of messengers at the plasma membrane that participate in the transition
from acute to chronic pain.
Key words
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Article info
Publication history
Published online: November 04, 2014
Accepted:
October 21,
2014
Received in revised form:
October 8,
2014
Received:
July 14,
2014
Footnotes
This study was funded by the National Institutes of Health (NIH), NS084545.
The authors declare no conflict of interest.
Identification
Copyright
© 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.
