Objective  Based on a complete Freund's adjuvant (CFA)-induced chronic inflammatory pain model, we compared and analyzed the differences in anti-inflammatory and analgesic effects of moxibustion intervention initiated at different timepoints, aiming to identify the optimal timing for moxibustion intervention. The goal is to establish standardized intervention protocols for basic research on the anti-inflammatory and analgesic effects of moxibustion.

Methods  Male C57BL/6 mice were randomly divided into 3 groups based on the moxibustion initiation timepoints of 4, 7, and 10 d after modeling. Then, the mice in each group were randomly assigned to 3 subgroups, including a control group, a model group, and a moxibustion group, with 8 mice in each subgroup. Chronic inflammatory pain was induced by injecting 20 μL of CFA into the sole of the right hind paw. Moxibustion applied at the "Zusanli" acupoint for 30 minutes started on the 4th, 7th, and 10th days after modeling, and the intervention continued for 7 days. The latency of paw withdrawal to thermal radiation was measured to evaluate the pain threshold before modeling, after modeling, and on the 1st, 4th, and 7th days of treatment. Foot volume was measured to assess toe swelling before modeling, after modeling, and on the 1st and 7th days of treatment.

Results  Compared with the control group, the model group exhibited a reduced pain threshold (P < 0.0001) and increased paw volume (P < 0.0001). Compared with the model group, the subgroups receiving moxibustion intervention initiated on the 4th, 7th, and 10th days post-modeling exhibited an increased pain threshold (P < 0.05, P < 0.0001). However, the paw volume of the subgroups receiving moxibustion intervention initiated on the 4th day post-modeling increased (P < 0.0001), while those of the subgroups receiving moxibustion intervention initiated on the 7th and 10th days post-modeling decreased (P < 0.0001). Among the intervention subgroups receiving moxibustion initiated on days 4, 7, and 10, the day 7 intervention-initiating subgroup showed significant increase in pain threshold (P < 0.05, P < 0.0001), and the day 7 and day 10 intervention-initiating subgroups showed significantly reduced paw volume (P < 0.0001).

Conclusion Considering both the analgesic and anti-inflammatory effects of moxibustion, day 7 post-modeling may be the optimal time for moxibustion to achieve effective anti-inflammatory and analgesic outcomes.