Abstract
Cancer patients often suffer from pain and most will be prescribed μ-opioids. μ-opioids
are not satisfactory in treating cancer pain and are associated with multiple debilitating
side effects. Recent studies show that μ and δ opioid receptors are separately expressed
on IB4 (−) and IB4 (+) neurons, which control thermal and mechanical pain, respectively.
In this study we investigated IB4 (+) and IB4 (−) neurons in mechanical and thermal
hypersensitivity in an orthotopic mouse oral cancer model. We used a δ opioid receptor
agonist and a P2X3 antagonist to target IB4 (+) neurons and to demonstrate that this subset plays a
key role in cancer-induced mechanical allodynia, but not in thermal hyperalgesia.
Moreover, selective removal of IB4 (+) neurons using IB4-saporin impacts cancer-induced
mechanical but not thermal hypersensitivity. Our results demonstrate that peripherally
administered pharmacological agents targeting IB4 (+) neurons, such as a selective
δ-opioid receptor agonist or P2X3 antagonist, might be useful in treating oral cancer pain.
Perspective
To clarify the mechanisms of oral cancer pain, we examined the differential role of
IB4 (+) and IB4 (−) neurons. Characterization of these 2 subsets of putative nociceptors
is important for further development of effective clinical cancer pain relief.
Key words
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Article Info
Publication History
Published online: April 09, 2012
Accepted:
January 16,
2012
Received in revised form:
January 2,
2012
Received:
August 2,
2011
Footnotes
This work was funded by NIH/NIDCR R21DE01856 .
The authors have no conflicts of interest to declare.
Identification
Copyright
© 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.
