Dynamic distributions of tumor necrosis factor-alpha and its receptors in the red nucleus of rats with spared nerve injury

Previous studies have demonstrated that tumor necrosis factor‐alpha (TNF‐α) in the red nucleus (RN) plays a facilitated role in the development of neuropathic pain, and its effect is transmitted through TNF‐α receptor (TNFR) subtypes 1 and 2. Here, the dynamic distributions of TNF‐α and TNFRs in the RN of rats with spared nerve injury (SNI) were investigated. Western blot analysis and immunofluorescence staining indicated that TNF‐α was hardly expressed in the RN of normal rats but significantly increased at 1 week and peaked at 2 weeks after SNI. Neurons and oligodendrocytes showed TNF‐α expression at both 1 week and 2 weeks after SNI, while astrocytes and microglia produced TNF‐α later than neurons and oligodendrocytes starting at 2 weeks after SNI. TNFR1 was constitutively expressed in the RN of normal rats and significantly enhanced at 2 weeks but not 1 week after SNI; it was mainly localized in neurons, oligodendrocytes and microglia. Astrocytes were not immunopositive for TNFR1 under normal conditions and at 1 week after injury, but small amounts of astrocytes showed TNFR1 expression at 2 weeks after SNI. A low level of TNFR2 was expressed in the RN of normal rats, but it was significantly increased at 1 week and 2 weeks after SNI and localized in neurons and all three types of glia. These findings suggest that neurons and three types of glia in the RN all contribute to TNF‐α production and participate in the initiation and/or maintenance of neuropathic pain induced by SNI. TNF‐α exerts its effects in different types of cells maybe through different receptors, TNFR1 and/or TNFR2, in the different stages of neuropathic pain.