Abstract
Stimulation of peripheral nociceptors results in increased c-Fos labeling in spinal
cord regions associated with nociceptive processing. Accordingly, intracolonic capsaicin,
which generates robust secondary (referred) allodynia on the abdomen of mice, also
causes an increased spinal c-Fos labeling. In naïve rodents, low intensity innocuous
stimulation does not affect c-Fos labeling in spinal nociceptive regions. However,
after persistent noxious input, low intensity stimulation of the inflamed region further
enhances c-Fos labeling, suggesting that low threshold mechanosensitive fibers gain
access to the nociceptive channel after persistent inflammation. We have previously
proposed that afferent activity in low threshold sensory fibers activates nociceptive
sensory fibers through Na+-K+-Cl− cotransporter 1 (NKCC1) -mediated enhanced primary afferent depolarization. Here,
we show that intracolonic capsaicin enhances spinal c-Fos labeling and secondary allodynia
in an NKCC1-dependent manner. Furthermore, we demonstrate that gently brushing the
abdomen, the region of secondary allodynia, further increased spinal c-Fos levels,
an effect that can be prevented by spinal NKCC1 blockade. These findings provide evidence
that increased NKCC1 activity contributes to secondary allodynia and that innocuous
touch can access the nociceptive channel in part through enhanced NKCC1 activity.
Perspective
While touch normally soothes acute pain, we demonstrate that following peripheral
inflammation, touch evokes pain (allodynia) through the switching of a normally inhibitory
spinal pathway into an excitatory pathway. Activation of low threshold mechanoreceptors
activates spinal nociceptive neurons following inflammation-induced enhancement of
NKCC1 expression, as measured by spinal c-Fos labeling.
Key words
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Article info
Publication history
Published online: November 29, 2012
Accepted:
October 4,
2012
Received in revised form:
October 1,
2012
Received:
June 8,
2012
Footnotes
Supported by the Louise & Alan Edwards Foundation. M.H. Pitcher was supported by a McGill University Faculty of Medicine Internal Fellowship. F.R. Nieto was supported by an FPU grant from the Spanish Ministry of Education and Science (MEC).
There is no conflict of interest among authors.
Identification
Copyright
© 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.
