Abstract
Introduction Emerging data show that chemokine-mediated inflammation is involved in the occurrence and maintenance of pain. Recent evidence suggests that eotaxin levels rise when dysmenorrhea happens. The purpose of this study is to investigate whether eotaxin/CC chemokine receptor 3 (CCR3) axis, a key regulatory pathway for eosinophils (EOS) recruitment, is involved in acupuncture analgesia for dysmenorrhea. Methods After the cold congealing dysmenorrhea (CCD) rat model prepared, animals received perpendicular needling (PN) and transverse needling (TN) at SP6, respectively, for 20 min. The CCR3 agonist CCL11 was administered 30 min prior to acupuncture. Pain behavior was assessed via a writhing response. The uterine contraction test was detected by an electrophysiological method. Eotaxin, histamine (HIS), and interleukin-6 (IL-6) levels were evaluated by ELISA. The expression of CCR3 and histamine H1 receptor (H1R) was analyzed by RT-qPCR and Western blot. The expression of EOS, mast cells (MCs), eosinophil peroxidase (EPO), and eosinophil cationic protein (ECP) was assessed by hematoxylin-eosin staining (HE), Toluidine Blue staining (TB), and immunohistochemistry, respectively. Results Acupuncture prominently attenuated the menstrual pain in CCD rats, particularly TN technique. Electrophysiological recording data showed that the increased uterine contractility was ameliorated by acupuncture. In addition, TN decreased the release of eotaxin, HIS, IL-6, and the expression of CCR3 and H1R. HE, TB staining, and immunohistochemistry experiments showed that the increased expression of EOS, MCs, EPO, and ECP in uterine tissues was reversed by TN. Furthermore, we found that the effects of TN against CCD-induced menstrual pain, increased ECP expression, and HIS level were abolished by CCL11. Conclusion TN alleviated menstrual pain by improving the uterine inflammatory environment via suppressing eotaxin/CCR3 axis to weak EOS-MC activation in CCD rats. The study findings support the acupuncture as a promising approach for dysmenorrhea, meanwhile, indicating the importance of performing appropriate needling technique.
Highlights
Emerging data show that chemokine-mediated inflammation is involved in the occurrence and maintenance of pain
EOS and mast cells (MCs) played essential roles in Evidence-Based Complementary and Alternative Medicine morphological changes associated with the menstrual cycle and were believed to be important inflammatory cells involved in uterine inflammatory microenvironment [7, 9]
A writhing score in 20 min significantly decreased in the Model + transverse needling (TN) group compared with the Model + perpendicular needling (PN) group (P < 0.05, Figure 2(c)), indicating that TN performs better in dysmenorrhea
Summary
Emerging data show that chemokine-mediated inflammation is involved in the occurrence and maintenance of pain. Recent evidence suggests that eotaxin levels rise when dysmenorrhea happens. E purpose of this study is to investigate whether eotaxin/CC chemokine receptor 3 (CCR3) axis, a key regulatory pathway for eosinophils (EOS) recruitment, is involved in acupuncture analgesia for dysmenorrhea. PD is commonly treated with nonsteroidal anti-inflammatory medications and oral contraceptives These drugs are accompanied by some side effects, such as headache, dizziness, fatigue, loss of appetite, nausea, vomiting, and drowsiness [4], and approximately 18% of women do not respond these [5]. A recent study has showed that the serum level of eotaxin is increased in patients with primary dysmenorrhea [15]. Erefore, inactivation of eotaxin/CCR3 axis weakening EOS-MC activation could be involved in anti-inflammatory and analgesic mechanism subsequently modulating menstrual pain Eosinophil cationic protein (ECP) has been shown to stimulate mast cells (MCs) to release histamine (HIS), which promotes uterine contractions and exacerbates pain [16]. erefore, inactivation of eotaxin/CCR3 axis weakening EOS-MC activation could be involved in anti-inflammatory and analgesic mechanism subsequently modulating menstrual pain
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