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Abstract: In prior studies, Eph/ephrin system was demonstrated to be involved in inflammatory and neuropathic pain modulation. The present study was to investigate whether the spinal Eph/ephrin signaling was involved in modulation of spinal inflammatory cytokines in bone cancer pain (BCP) of rats. BCP was induced by intra-tibial inoculation of Walker 256 mammary gland carcinoma cells. The expressions of EphB1/ephrinB1 in spinal cord (SC) and dorsal root ganglia (DRG) were determined. At 16 days post inoculation, the pain relieving effect and the mRNA levels of inflammatory cytokines were detected after intrathecal administration of EphB1-Fc (blocker of EphB1 receptor, 10μg). The results showed that the EphB1/ephrinB1 expression was significantly increased in SC, but ephrinB1 was decreased in DRG after Walker 256 inoculation. The mechanical allodynia induced by bone cancer was significantly alleviated by intrathecal administration of EphB1-Fc. Furthermore, the RT-PCR analysis showed that the mRNA levels of IL-1β, IL-6 and TNF-α were significantly increased at 16 days post Walker 256 inoculation and were significantly suppressed by intrathecal administration of EphB1-Fc in SC. We concluded that Eph/ephrin might be involved in the maintenance of mechanical allodynia, via modulating the expression of spinal inflammatory cytokines, in the present rat model of BCP. This study suggested that Eph/ephrin signaling would be a potential target for the treatment of BCP. [Copyright &y& Elsevier]

Abstract: Osteomyelitis is an acute or chronic inflammatory process of bone accompanied with mild to severe pain. Generally, mild to moderate pain induced by osteomyelitis can be relieved, yet severe pain cannot. Therefore, a further investigation into the mechanism of severe pain induced by osteomyelitis is needed. In this study, a traditional rat model of osteomyelitis was induced by intra-tibial injection of Staphylococcus aureus. Then, a series of tests including bone histology, blood analysis, mechanical allodynia, thermal hyperalgesia, and immunohistochemistry were performed. Four days after an intra-tibial bacterial injection, acute inflammation was observed in the bone marrow, which developed into chronic inflammation 12 days after the procedure. The results from the blood analysis confirmed the existence of bone inflammation. Significant mechanical allodynia and thermal hyperalgesia developed shortly after the injection. This osteomyelitis-induced pain behavior was reversed by Celecoxib, a selective COX-2 inhibitor. Furthermore, significant increase of both microglia and astrocytes was observed in the spinal cord. Our results suggest that osteomyelitis-induced rats display pain related behaviors and associated neurochemical changes. This study thus provides a novel practical rat model of bone inflammation induced pain. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]