ObjectiveTo investigate the differences between immune-related pain induced by antigen-specific immune complex and inflammatory pain induced by formalin. MethodsFifteen adult health SD rats were randomly divided into control group, formalin group and immune-complex group with 5 rats in each group. The right hindpaws of rats were respectively injected with PBS, formalin and rat IgG immune-complex. The changes of hindpaw thickness and pain behavior were observed at 0,0 min, 1 h, 2 h, 4 h, 8 h and 12 h after injection. Serum macrophage migration-inhibitory factor (MIF) was detected by ELISA. Expression of MIF in the hindpaw skin and spinal cord was determined by RT- PCR. Results1. Changes of nociceptive behavior:rats in the formalin group showed significant nociceptive behavior immediately, such as licking foot, limping and highly swollen foot which could not touch the ground. Abnormal nociceptive behavior was lasting more than 1 hour after injection and alleviated after then. Pain threshold of rats in the immune complex group obviously decreased at 4 hours after injection without red swollen hindpaw. Expression of MIF of skin and spinal cord in the rats of formalin group were significantly higher than that in the control group (P<0.05). There was statistically not significant difference of MIF expression between the immune complex group and control group. ConclusionsMacrophage migration inhibitory factor contributes to the pathogenesis of inflammatory pain. But no evidence shows that MIF also anticipates in the pathogenesis of immune-related pain. There are some differences in the mechanisms of the immune-related pain and inflammatory pain induced by formalin.