Erythropoietin and erythropoietin receptors in the peripheral nervous system: changes after nerve injury

Erythropoietin (Epo) is a hematopoietic factor that has recently been shown to function in the central nervous system. The presence or function of Epo or the erythropoietin receptor (EpoR) in the peripheral nervous system is unknown. Our results demonstrate the presence of both Epo and EpoR in the rat sciatic nerve. Epo was present in axons and was up-regulated in Schwann cells after chronic constriction injury (CCI). EpoR was present in endothelial cells, cell bodies of the dorsal root ganglia (DRG), axons, and Schwann cells; it was not changed after injury. Using two different models of nerve injury, CCI and crush injury adjacent to the DRG, we demonstrated TUNEL labeling in DRG cell bodies after adjacent nerve crush, but not after CCI. TUNEL labeling in crush injury correlated with a significant reduction of EpoR in DRG as determined by morphometry and Western blotting. Immunoblotting of uninjured DRG homogenates revealed an immunoreactive band at 90 kDa and 70 kDa. After crush injury, both 70 kDa and 90 kDa proteins were reduced and the 90 kDa protein showed enhanced tyrosine phosphorylation, whereas the 70 kDa showed less. EpoR colocalized with NF200 in normal DRG, but not after crush injury to the adjacent axon. These findings demonstrate Epo and EpoR in the peripheral nervous system and their regulation after painful nerve injury.