Abstract. The classical analgesic pathway of opioids by binding their receptors in the nervous system is well known. However, little is known regarding opioid analgesia through the anti-inflammatory pathway. The present study aimed to investigate the analgesic and anti-inflammatory effect of β-endorphin on inflammatory pain. A rat model of collagen-induced arthritis (CIA) was generated by intradermal injection of bovine type II collagen. Rats were divided into the CIA + saline group and the CIA + β-endorphin group, in which rats were intraperitoneally injected with β-endorphin once every other day from day 18 following the injection of CII until day 28. Thermal hyperalgesia as determined by tail flick latency (TFL), as well as paw arthritis index and swelling. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 mRNA expression in synovial tissue and their protein levels in paw inflammatory tissue were measured. The rat CIA model was successfully induced as indicated by the significantly decreased TFL, increased paw arthritis index and percentage of swelling on day 18. β-endorphin treatment significantly increased the TFL, while decreasing the paw arthritis index and swelling in CIA rats. It also significantly downregulated TNF-α and IL-1β mRNA expression in synovial tissue and their protein levels in inflammatory tissue of the paws of CIA rats, while it had no significant effect on the levels of IL-6. These results indicated that β-endorphin suppresses peripheral pro-inflammatory mediators in collagen-induced arthritis, which may contribute to its analgesic effect.
IntroductionThe analgesic effect of opioids has been well demonstrated in animal behavioral studies as well as human clinical trials (1,2). Opioids are potent analgesics, which exert their pharmacological effects by binding and activating specific receptors in the nervous system (3,4). Accumulating evidence has demonstrated that opioids also exert an immunomodulatory function (5). Under inflammatory conditions, local inflammatory cells, including monocytes, granulocytes, lymphocytes and macrophages, synthesize and release opioids (6). Opioids also bind to receptors on immune cells to regulate inflammatory cytokines, which may constitute another mechanism of opioid-induced analgesia (7).Rheumatoid arthritis (RA) is a chronic, systemic type of autoimmune inflammatory arthritis, which may lead to severe joint pain, as well as destruction of cartilage and bone (8). A large number of cytokines, including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α are active in the joints of patients with RA. These cytokines have a fundamental role in RA pathology, causing inflammation, pain and articular destruction (9). Previous studies have indicated that injection of opioids into knee joints after surgery caused prolonged post-operative analgesia in patients (10-12), which may be associated with their immunomodulatory function. Based on these results, the present study hypothesized that opioids also produce analgesic effects on RA via regulating...