Adenosine A2A Receptors Mediate Anti-Inflammatory Effects of Electroacupuncture on Synovitis in Mice with Collagen-Induced Arthritis

Abstract

To study the role of adenosine A2A receptor (A2AR) in mediating the anti-inflammatory effect of electroacupuncture (EA) on synovitis in collagen-induced arthritis (CIA), C57BL/6 mice were divided into five treatment groups: Sham-control, CIA-control, CIA-EA, CIA-SCH58261 (A2AR antagonist), and CIA-EA-SCH58261. All mice except those in the Sham-control group were immunized with collagen II for arthritis induction. EA treatment was administered using the stomach 36 and spleen 6 points, and stimulated with a continuous rectangular wave for 30 min daily. EA treatment and SCH58261 were administered daily from days 35 to 49 (n = 10). After treatment, X-ray radiography of joint bone morphology was established at day 60 and mouse blood was collected for ELISA determination of tumor necrosis factor alpha (TNF-α) levels. Mice were sacrificed and processed for histological examination of pathological changes of joint tissue, including hematoxylin-eosin staining and immunohistochemistry of A2AR expression. EA treatment resulted in significantly reduced pathological scores, TNF-α concentrations, and bone damage X-ray scores. Importantly, the anti-inflammatory and tissue-protective effect of EA treatment was reversed by coadministration of SCH58261. Thus, EA treatment exerts an anti-inflammatory effect resulting in significant protection of cartilage by activation of A2AR in the synovial tissue of CIA.

Effective treatment of polydatin weakens the symptoms of collagen-induced arthritis in mice through its anti-oxidative and anti-inflammatory effects and the activation of MMP-9

“…Through the release of type II collagen, mice are able to induce an autoimmune response, leading to the erosion of cartilage in type II collagen-mediated multi-arthritis, which is known as CIA (8). The characteristics of CIA are similar in several ways to those of human RA, including synovitis, the formation of cartilage and subchondral pannus, inflammatory cell infiltration, the erosion of cartilage, bone resorption and remodeling, and so forth (9). Therefore, CIA is regarded as a unique animal model of human RA, which is therefore widely used in studies on the mechanism of RA.…”

“…Free radicals are involved in the occurrence and development of RA, in the process of synovial inflammatory lesions of the joints, and in bone destruction; additionally, free radicals are directly or indirectly involved in synovial membrane and bone injuries (8,9). All types of free radicals are involved in this process: Hydroxyl free radicals biodegrade proteoglycan, hypochlorous acid leads to the fracture of the collagen, and the capability of hydrogen peroxide to diffuse throughout the tissue leads to the inhibition of cartilage glycoprotein synthesis and obstruction of the synthesis of ATP.…”

“…Local inflammation of the joints is a key link in the process of its pathogenesis; bone loss or damage caused by inflammation is the result of changes to the joints in RA, and symptoms of pain associated with joint swelling are often the most severe symptoms of which the patient complains (9). Therefore, inhibiting the inflammation has become one of the predominant targets of the clinical treatment (16).…”

Tackling Chronic Pain and Inflammation through the Purinergic System

“…Although few data are currently available, it is conceivable that other ARs apart from A 1 ARs are also involved, based on the above-mentioned evidence of their key role in specific types of pain and inflammatory conditions. One single report shows that A 2A ARs mediate the analgesic effects of EA on synovitis in collagen-induce arthritis (i.e., a type of inflammatory pain) [157], while the recruitment of A 3 ARs in the treatment of neuropathic pain can at the moment only be hypothesized, based on the role exerted by this receptor subtype in neuropathic pain (see 2.2).…”

Placenta Therapy: Its Biological Role of Anti-Inflammation and Regeneration

“…This activation is demonstrated to elicit profound physiological effects and even activate self-healing mechanisms [33]. Although the effect of manual acupuncture or electro-acupuncture is comparative to the effects of nonsteroidal anti-inflammatory drugs and opioid analgesics [34], maintenance of needles might be cumbersome, particularly in agitated animals. In order to overcome this disadvantage, other techniques might be used for stimulation of acupuncture points.…”