Objective: To investigate the analgesic time-effect characteristics and changes in concentrations of rabbit’s hypothalamic 5-hydroxytryptamine (5-HT) and noradrenaline (NE) caused by buccal acupuncture in the rheumatoid arthritis (RA) rabbits, and to reveal the analgesic central mechanism of buccal acupuncture, thereby providing a theoretical basis for the treatment of pain by buccal acupuncture.Methods: Forty rabbits were randomly divided into a normal group, a model group, a body acupuncture group, and a buccal acupuncture group, with 10 rabbits in each group. No model was established in the normal group, while equal dose of normal saline was injected at the matched site and time point; rabbits in other groups were subjected to the establishment of RA models using egg protein. From the 27th day of the experiment, rabbits in each group received the designated intervention. Rabbits in the normal group and the model group were fixed for 30 min every day using the same method as those in the other groups. In the acupuncture group, Dubi (ST 35) and Zusanli (ST 36) on bilateral hind limbs were selected. Perpendicular needling (using the needles with 0.25 mm in diameter and 25 mm in length) was performed with twirling manipulation for 15 s at intervals of 5 min. The needles were retained for 30 min and acupuncture was performed once a day. In the buccal acupuncture group, the knee point in the buccal acupuncture and needles with a diameter of 0.25 mm and a length of 15 mm were selected. Oblique needling was performed with twirling manipulation for 15 s at intervals of 5 min. The needles were retained for 30 min and acupuncture was performed once a day. The thermal pain thresholds at the 0, 5, 15, 30, 60, 120 and 240 min after the 1st and 10th acupuncture therapy were measured with a PL-200 thermal-inducing pain meter. After the 10th acupuncture therapy, rabbit’s hypothalamus was removed, and the 5-HT and NE concentrations in the hypothalamus at the peak point of the acupuncture pain threshold curve were determined by high performance liquid chromatography (HPLC).Results: The analgesic effect was obvious at 5 min after buccal acupuncture started, peaked at 30 min, and decreased to the lowest value at 240 min. Rabbits in the body acupuncture group began to show significant analgesic effect at 15 min, which was peaked at 30 min, and began to decline at 60 min. The pain threshold at 240 min was still higher than that at 0 min. Compared with the model group, the concentrations of hypothalamic 5-HT in the buccal acupuncture group and the body acupuncture group was significantly increased, and the between-group differences were statistically significant (both P<0.05). The NE/5-HT ratios in hypothalamus in the buccal acupuncture group and the body acupuncture group were significantly lower than the ratio in the model group, and the differences were statistically significant (both P<0.05); difference in the decrease was statistically significant between the buccal acupuncture group and the body acupuncture group (P<0.05).Conclusion: The analgesic effect of buccal acupuncture shows an obvious time-dependent curve. It is characterized by rapid onset of pain relief, rapid increase and decline in pain threshold. 5-HT and NE levels in rabbit’s hypothalamus can be affected by buccal acupuncture, with increased 5-HT concentration and reduced NE/5-HT ratio. [ABSTRACT FROM AUTHOR]