Abstract
Therapeutic management of chronic pain has not been widely successful owing to a lack
of understanding of factors that initiate and maintain the chronic pain condition.
Efforts to delineate the mechanisms underlying pain long have focused on neuronal
elements of pain pathways, and both opiate- and non–opiate-based therapeutics are
thought largely to target neurons. Abnormal neuronal activity at the level of spinal
cord “pain centers” in the dorsal horn leads to hypersensitivity or a hyperalgesic
response subsequent to the initial painful stimulus. Only recently has the experimental
literature implicated nonneuronal elements in pain because of the realization that
glial-derived signaling molecules can contribute to and modulate pain signaling in
the spinal cord. Most notably, glial proinflammatory mediators within the dorsal horn
of the spinal cord appear to contribute to self-perpetuating pain. Chronic pain is
modeled experimentally through a variety of manipulations of sensory nerves including
cutting, crushing, resection, and ligation. The cellular and molecular responses in
the spinal cord due to these manipulations often reveal activation of 2 types of glia:
microglia and astrocytes. The activation states of both microglia and astrocytes are
complex and may be driven by underlying chronic neuropathology and/or a chronically
“primed” condition that accounts for their contribution to chronic pain. Recent evidence
even suggests that opioid tolerance and withdrawal hyperalgesia may be initiated and
maintained via actions of microglia and astroglia. Together, these recent findings
suggest that glia will serve as novel therapeutic targets for the treatment of chronic
pain. To fully exploit glia as novel therapeutic targets will require a greater understanding
of glial biology, as well as the identification of agents able to control the glial
reactions involved in chronic pain, without interfering with beneficial glial functions.
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Article info
Footnotes
Publication of this article was supported by the Collège International de Recherche Servier (CIRS).
STATEMENT OF CONFLICT OF INTEREST: The authors have nothing to disclose.
Identification
Copyright
© 2010 Published by Elsevier Inc.
