The effects of the cholinergic system on carrageenan-induced arthritis

The cholinergic system has been found to make an anti-inflammatory effect through the cholinergic antiinflammatory pathway (CAIP), which suppresses the production of pro-inflammatory cytokines by secreting acetylcholine, a major neurotransmitter. However, no studies have been conducted on the effects of CAIP on joint pain and inflammation. In this study, we investigated the effects of muscarinic acetylcholine receptors (mAChRs) in knee arthritis. To examine pain behavioral changes, atropine (or saline for sham control) was pretreated in the joint cavity of rats at 1 % carrageenan + 5, 10, and 30 mu L and the dynamic weight-bearing evaluation was performed. Synovial membranes were collected and cyclooxygenase-2 (COX-2) and interleukin-1 beta (IL-1 beta) were measured using a western blot. Hematoxylin and eosin staining was performed. Compared to that of the sham group, the weight-bearing of the affected knee joint significantly increased in the 1 % carrageenan + 10 mu L atropine group (p < 0.05). However, no significant changes were observed in the 1 % carrageenan + 5 and 30 mu L atropine groups. COX-2 and IL-1 beta and the number of inflammatory cells in synovial membrane significantly increased with 1 % carrageenan + 10 mu L of atropine (p < 0.05). These results suggest that cholinergic system is involved in knee joint pain and inflammation and that mAChRs are potential therapeutic targets for knee joint arthritis.