Investigation of Neuroprotective Effects of Erythropoietin on Chronic Neuropathic Pain in a Chronic Constriction Injury Rat Model

J Pain Res. 2020 Nov 30:13:3147-3155. doi: 10.2147/JPR.S285870. eCollection 2020.

Abstract

Introduction: Neuropathic pain is pretty common in modern society, and the treatment effect is far from satisfactory. This study aimed to find evidence of the neuroprotective effect of erythropoietin (EPO) in the treatment of neuropathic pain in a rat model of chronic constriction injury (CCI).

Methods: A total of 30 rats were randomly divided into sham operation group, CCI group, or CCI+EPO group. The mechanical and thermal nociception thresholds are evaluated as behavioral assessments. The dorsal root ganglion cells were morphologically evaluated by hematoxylin and eosin staining, and AMPK, p-AMPK, mTOR, p70S6K, and AQP-2 proteins were compared and analyzed by Western blotting. Compared with the sham operation group, rats in the CCI group had shorter paw withdrawal threshold and paw withdrawal latency, abnormal morphology, and increased satellite glial cells.

Results: After treatment with EPO, these changes were significantly reversed. In vivo administration of erythropoietin seems to be able to regulate the expression of AQP-2 through the AMPK/mTOR/p70S6K pathway. Our study provides behavioral, morphological, and immunoblot evidence to prove the neuroprotective effect of EPO in the treatment of chronic neuropathic pain in the CCI rat model.

Conclusion: Our results indicate that EPO has the potential to treat neuropathic pain caused by peripheral nerve injury, although further verification is needed.

Keywords: AQP-2; chronic contractile injury; dorsal root ganglia; erythropoietin; neuropathic pain; satellite glial cells.

Grants and funding

This research was funded by the Henan Provincial Medical Science and Technology Research Project (No. SBGJ2018030).