A rat model of bone inflammation-induced pain by intra-tibial complete Freund's adjuvant injection

In prior studies, models of inflammatory pain were produced through injecting complete Freund's adjuvant (CFA) or capsaicin directly into either the deep somatic tissue or the animal's hind paw. In contrast, bone cancer-induced pain (BCIP) was simulated through injecting tumor cells into the cavity of the femur or the tibia. It has been reported that, due to differences in afferent innervation, the same stimulus to various tissue types might result in differing patterns of pain response. Hence, the aim of this study is to establish a rat model of bone inflammation-induced pain (BIIP) by injecting CFA into the tibial cavity, the same site involved in the BCIP model. The differences in body weight, bone histology, mechanical allodynia, thermal hyperalgesia, and the pain relieving effects of Celebrex on this model of BIIP were evaluated. The results showed that there was evidence of significant inflammation seen in the bone marrow two days after intra-tibial CFA injection, including nuclear condensation and fragmentation, massive neutrophilic granulocytes, and prominent fibrinous exudates. Fourteen days after injection, marked fibrosis of the bone was detected by histological staining. After unilateral CFA injection, behavioral studies showed mechanical allodynia to von Frey hair stimulation, but no thermal hyperalgesia was observed. Celebrex showed significant anti-allodynic effects on the BIIP model. The results demonstrated that CFA is an effective agent for inducing bone inflammation and subsequent pain-related behavior in rat models, and, thus, provides a practical and valuable contrast for BCIP research.