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 r at sciatic nerve. Epo was present in axons and was up-regulated in Schwann cells after chronic constriction injury (CCI). EpoR was present in endothel ial cells, cell bodies of the dorsal root ganglia (DRG), axons, and Schwann cells; it was not changed after injury. Using two different models of nerv e injury, CCI and crush injury adjacent to the DRG, we demonstrated TUNEL l abeling in DRG cell bodies after adjacent nerve crush, but not after CCI. T UNEL labeling in crush injury correlated with a significant reduction of Ep oR 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 a nd the 90 kDa protein showed enhanced tyrosine phosphorylation, whereas the 70 kDa showed less. EpoR colocalized with NF200 in normal DRG, but not aft er crush injury to the adjacent axon. These findings demonstrate Epo and Ep oR in the peripheral nervous system and their regulation after painful nerv e injury.