Acupuncture reduces pain in rats with osteoarthritis by inhibiting MCP2/CCR2 signaling pathway

Acupuncture has emerged as a promising alternative for the treatment of pain related to osteoarthritis, a condition that affects more than 300 million people worldwide. Osteoarthritis is characterized by the degeneration of articular cartilage and subchondral bone, causing pain, swelling, stiffness, and often leading to joint dysfunction. Although it is not considered primarily an inflammatory disease, osteoarthritis often presents with low-grade inflammation and elevated levels of inflammatory substances in the synovial fluid. The exact mechanism by which acupuncture provides pain relief was not yet fully understood, especially in relation to the molecular processes involved.

This study aimed to investigate how acupuncture acts in the relief of osteoarthritis pain, focusing specifically on the MCP1/CCR2 signaling pathway. To do so, the researchers used male Sprague-Dawley rats in which osteoarthritis was induced through transection of the anterior cruciate ligament in the right knee. Electroacupuncture treatment was applied at points ST-35 and ST-36, located near the knee, beginning seven days after surgery and continuing daily for seven weeks. The animals were divided into different groups: control, osteoarthritis model, acupuncture-only treatment, CCR2 inhibitor-only treatment (RS504393), and combined treatment.

During the study, pain-related behaviors, histological alterations of cartilage, density of nerve fibers, and expression of various proteins important in the pain and inflammation process were evaluated.

The results demonstrated that electroacupuncture at points ST-35 and ST-36 was effective in significantly reducing both hyperalgesia and cartilage degeneration in animals with osteoarthritis. Acupuncture treatment decreased the density of nerve sprouting in the knee joint, which is directly related to pain perception. More importantly, the researchers discovered that acupuncture works by inhibiting the MCP1/CCR2 pathway, which is responsible for attracting inflammatory cells such as monocytes and macrophages to the joint. This inhibition results in decreased production of nerve growth factor (NGF), a protein that stimulates the growth of nerve fibers and intensifies the sensation of pain.

Examinations showed that acupuncture also reduced the expression of inflammatory cytokines such as IL-1β and TNF-α in both cartilage and synovial tissue.

For patients suffering from osteoarthritis, these findings offer a solid scientific explanation of how acupuncture can provide pain relief naturally. The study suggests that acupuncture did not merely mask symptoms, but acted on the fundamental mechanisms that cause pain and inflammation in osteoarthritis. For healthcare providers, these results provide evidence that acupuncture can be considered an evidence-based therapeutic option, especially considering that conventional pharmacologic treatments, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, present significant limitations and are unable to prevent, slow, or halt the structural alterations of osteoarthritis. The discovery that acupuncture acts through modulation of the MCP1/CCR2 pathway opens possibilities for the development of more specific and effective treatment protocols.

It is important to acknowledge the limitations of this study. First, the research was conducted in an animal model, which means that the results need to be validated in clinical studies with human patients before we can have absolute certainty about its clinical applicability. In addition, the researchers did not perform double labeling to directly confirm that macrophages in the synovium are truly the main source of NGF, although indirect evidence suggests this relationship. The study also focused only on cartilage and synovial tissue, not examining the subchondral bone, which also plays an important role in the pathophysiology of osteoarthritis.

Despite these limitations, the research represents a significant advance in the understanding of the molecular mechanisms of acupuncture, offering a solid scientific basis for its use in the treatment of osteoarthritis and potentially opening paths for the development of new therapeutic approaches that combine the benefits of traditional medicine with the modern understanding of pain and inflammation processes.