Biphasic activation of extracellular signal-regulated kinase in anterior cingulate cortex distinctly regulates the development of pain-related anxiety and mechanical hypersensitivity in rats after incision
Date
2011
Authors
Dai, R.
Li, C.Q.
Zhang, J.W.
Li, F.
Shi, X.
Zhang, J.
Zhou, X.F.
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Advisors
Journal Title
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Journal article
Citation
Anesthesiology, 2011; 115(3):604-613
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Abstract
Background: A recent study has demonstrated that surgical incision induces an anxiety-like behavior but its relationship with incision-evoked mechanical hypersensitivity remains elusive. Extracellular signal-regulated kinase (ERK) activity in the anterior cingulate cortex (ACC) is important for the affective pain. The current study aims to explore ERK1/2 activity in the ACC and its role in the development of anxiety and mechanical hypersensitivity after incision.
Conclusions: These data suggest that in the early phase of postoperative pain, pain-related anxiety and mechanical hypersensitivity are tightly linked and regulated by the ERK activation in the ACC. However, in the late phase of postoperative pain, ERK activation in the ACC is only required for the expression of pain-related anxiety but not mechanical hypersensitivity.
Methods: Anxiety-like behavior was measured by elevated plus maze experiment and open field test after hind paw incision. ERK1/2 phosphorylation was determined by immunohistochemistry and Western blot. Cannulae were implanted into the bilateral ACC for the intra-ACC injection of ERK inhibitors PD98059 and U0126. Brushing (innocuous stimulus) was used to investigate its effect on ERK activation under the incision-evoked painful condition.
Results: The anxiety-like behavior induced by the hind paw incision persisted longer than mechanical hypersensitivity. One hind paw incision resulted in a biphasic ERK activation in bilateral ACC. Inhibiting ERK activation in the early phase attenuated pain-related anxiety and mechanical hypersensitivity whereas inhibiting ERK activation in the late phase only reduced the anxiety-like behavior. During the time interval between two phases of ERK activation, brushing the incised skin dramatically increased ERK phosphorylation in the ACC.
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Dissertation Note
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Link to a related website: http://anesthesiology.pubs.asahq.org/data/journals/jasa/931109/0000542-201109000-00027.pdf, Open Access via Unpaywall
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Copyright 2011 the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins.