Comorbidity of chronic pain and major depression disorder (MDD) are common diseases. However, the mechanisms of electroacupuncture (EA) and the responses of N-methyl-D-aspartate receptors in the brain remain unclear. Three injections of complete Freund's adjuvant (CFA) were administered to induce chronic inflammatory pain (CIP). EA was then performed once every other day from days 14 to 28. Behavior tests of chronic pain and depression were evaluated to make sure of the successful induction of comorbidity. We used Western blotting to analyze brain tissue from the prefrontal cortex (PFC), hippocampus, and hypothalamus for levels of phosphorylated N-methyl-D-aspartate receptor subunit 1 (pNR1), NR1, pNR2B, NR2B, and calcium/calmodulin-dependent protein kinase type II alpha isoform (pCaMKIIα). The mechanical hyperalgesia, thermal hyperalgesia, and depression were observed in the CIP group. Furthermore, decreased levels of N-methyl-D-aspartate receptors (NMDARs) were also noted. Not Sham EA but EA reversed chronic pain and depression as well as the decreased levels of NMDA in the signaling pathway. The CFA injections successfully induced a significant comorbidity model. EA treated the comorbidity by upregulating the NMDA signaling pathway in the PFC, hippocampus, and hypothalamus. Our results indicated significant mechanisms of comorbidity of chronic pain and MDD and EA-analgesia that involves the regulation of the NMDAR signaling pathway. These findings may be relevant to the evaluation and treatment of comorbidity of chronic pain and MDD.

The glucose-lowering effect and increased insulin sensitivity associated with EA-metformin administration is governed, at least in part, by its ability to stimulate the activation of GLUT4 via upregulation of MAPK expression.

Background The treatment, and efficacy thereof, is considered to be inadequate with specificity to alleviation of Fibromyalgia and its associated pain. Fibromyalgia patients suffer from chronic and persistent widespread pain and generalized tenderness. Transient receptor potential V1 (TRPV1), which is reported as a Ca2+ permeable ion channel that can be activated by inflammation, is reported to be involved in the development of fibromyalgia pain. Methods The current study explored the TRPV1 channel functions as a noxious sensory input in mice cold stress model. It remains unknown whether electroacupuncture (EA) attenuates fibromyalgia pain or affects the TRPV1 pathway. Results We show that cold stress increases mechanical and thermal pain (day 7: mechanical: 1.69 ± 0.41 g; thermal: 4.68 ± 0.56 s), and that EA and Trpv1 deletion counter this increase. EA and Trpv1 deletion reduced the cold stress-induced increase in inflammatory mediators and TRPV1-related molecules in the hypothalamus, periaqueductal gray (PAG), and cerebellum of mice. Conclusions Our results imply that EA has an analgesic effect associated with TRPV1 downregulation. We provide novel evidence that these inflammatory mediators can modulate the TRPV1 signaling pathway and suggest new potential therapeutic targets for fibromyalgia pain.