Spinal AMPA Receptor GluA1 Ser831 Phosphorylation Controls Chronic Alcohol Consumption-Produced Prolongation of Postsurgical Pain
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Previous studies have shown that excessive alcohol drinking is associated with chronic pain development; however, the molecular mechanism underlying this association is poorly understood. In this study, we investigated the effect of chronic alcohol consumption on plantar incision-induced postsurgical pain. We observed that 4-week ethanol drinking significantly prolonged plantar incision-induced mechanical pain, but not thermal pain. The chronic alcohol consumption enhanced plantar incision-produced α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA1 phosphorylation at the Ser831 site in the spinal cord. The targeted mutation of the GluA1 phosphorylation site in GluA1 S831A mutant mice significantly inhibited the incisional pain prolongation produced by chronic alcohol consumption. Moreover, chronic alcohol consumption combined with plantar incision markedly increased AMPA receptor-mediated miniature excitatory postsynaptic currents in the spinal dorsal horn neurons, and this effect was diminished significantly in the GluA1 S831A mutant mice. Our results suggest that chronic alcohol consumption may promote the development of persistent postsurgical pain by enhancing AMPA receptor GluA1 Ser831 phosphorylation. We identified chronic alcohol consumption as a risk factor for pain chronification after surgery.
KeywordsChronic alcohol consumption Postsurgical pain AMPA receptor phosphorylation Pain chronification
This work was supported by National Institutes of Health Grants R01 DE022880 (F.T.) and K02 DE023551 (F.T.) as well as National Natural Science Foundation of China 81500962 (S.L.). The authors thank Dr. Richard Huganir (Johns Hopkins University School of Medicine) for providing AMPA receptor GluA1 S831A phospho-deficient mutant mice.
Compliance with Ethical Standards
All animal procedures were carried out in accordance with the National Institutes of Health guide for the care and use of laboratory animals and were approved by the Texas A&M University College of Dentistry Institutional Animal Care and Use Committee.
Conflicts of Interest
The authors declare that they have no conflict of interest.
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