Abstract
Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a multifunctional serine/threonine kinase that is ubiquitously distributed in the central and peripheral nervous systems. Moreover, its phosphorylated protein (P-CaMKII) is involved in memory, mood, and pain regulation in the anterior cingulate cortex (ACC). Electroacupuncture (EA) is a traditional Chinese therapeutic technique that can effectively treat chronic inflammatory pain. However, the CaMKII-GluA1 role in EA analgesia in the ACC remains unclear. This study investigated the role of P-CaMKII and P-GluA1 in a mouse model of inflammatory pain induced by complete Freund's adjuvant (CFA). There were increased P-CaMKII and P-GluA1 levels in the ACC. We found that intracerebroventricular injection of KN93, a CaMKII inhibitor, as well as EA stimulation, attenuated complete Freund's adjuvant-induced pain behavior. Further, EA increased pCaMKII-PICK1 complex (abbreviated as C-P complex) levels. Our findings demonstrate that EA inhibits inflammatory pain by inhibiting CaMKII-GluA1 phosphorylation. P-CaMKII is involved in EA analgesia as the pCaMKII-PICK1 complex.
Highlights
Inflammatory pain is a common condition that is difficult to clinically treat
These findings indicate that EA on Zusanli acupoints can relieve complete Freund’s adjuvant (CFA)-induced inflammatory pain
We previously reported that PICK1 is involved in the EA analgesic effect [32]
Summary
Inflammatory pain is a common condition that is difficult to clinically treat. It involves both cellular and noncellular immunity [1, 2]. Its clinical characteristics include decreased pain threshold, enhanced pain response, and spontaneous pain [3]. According to the theory of Chinese medicine, there are hundreds of acupuncture points in the human body; acupuncture points, especially the Zusanli and Sanyinjiao points, can be stimulated to relieve pain [4, 5]. The World Health Organization has reported that acupuncture can treat 77 diseases [6]. Electroacupuncture (EA) is widely used in clinical practice [7,8,9,10]
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