Stress Induces Pain Transition by Potentiation of AMPA Receptor Phosphorylation
- Changsheng Li1,5,*,
- Ya Yang1,2,*,
- Sufang Liu1,5,*,
- Huaqiang Fang3,
- Yong Zhang1,
- Orion Furmanski1,
- John Skinner1,
- Ying Xing5,6,
- Roger A. Johns1,
- Richard L. Huganir3,4, and
- Feng Tao1,7
- 1Department of Anesthesiology and Critical Care Medicine,
- 2The Russell H. Morgan Department of Radiology and Radiological Science,
- 3Solomon H. Snyder Department of Neuroscience, and
- 4Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205,
- 5Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, People's Republic of China,
- 6Basic Medical College, Xinxiang Medical University, Xinxiang, Henan 453003, People's Republic of China, and
- 7Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, Texas 75246
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Author contributions: R.L.H. and F.T. designed research; C.L., Y.Y., S.L., and F.T. performed research; C.L., Y.Y., S.L., H.F., Y.Z., O.F., J.S., Y.X., R.A.J., R.L.H., and F.T. analyzed data; R.L.H. and F.T. wrote the paper.
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↵*C.L., Y.Y., and S.L. contributed equally to this work.
Abstract
Chronic postsurgical pain is a serious issue in clinical practice. After surgery, patients experience ongoing pain or become sensitive to incident, normally nonpainful stimulation. The intensity and duration of postsurgical pain vary. However, it is unclear how the transition from acute to chronic pain occurs. Here we showed that social defeat stress enhanced plantar incision-induced AMPA receptor GluA1 phosphorylation at the Ser831 site in the spinal cord and greatly prolonged plantar incision-induced pain. Interestingly, targeted mutation of the GluA1 phosphorylation site Ser831 significantly inhibited stress-induced prolongation of incisional pain. In addition, stress hormones enhanced GluA1 phosphorylation and AMPA receptor-mediated electrical activity in the spinal cord. Subthreshold stimulation induced spinal long-term potentiation in GluA1 phosphomimetic mutant mice, but not in wild-type mice. Therefore, spinal AMPA receptor phosphorylation contributes to the mechanisms underlying stress-induced pain transition.
- Received May 26, 2014.
- Revision received August 28, 2014.
- Accepted September 3, 2014.
- Copyright © 2014 the authors 0270-6474/14/3413737-10$15.00/0
