Effects of recombinant human erythropoietin on neuropathic pain and cerebral expressions of cytokines and nuclear factor-kappa B

Abstract

The effect of recombinant human erythropoietin (rhEPO) on neuropathic pain remains unclear. This study aimed to determine the effects of preemptive administration of rhEPO on the behavioural changes and neuroinflammatory responses in a rat model of neuropathic pain. Fifty rats were randomly allocated into five groups, sham-operation treated with saline and L5 spinal nerve transection treated with different doses of rhEPO (0 [saline], 1000, 3000, or 5000 U x kg(-1), respectively). The rats were intraperitoneally treated from 1 day before surgery to post-surgery day 7. The mechanical (paw pressure thresholds, PPT) and thermal thresholds (paw withdrawal latencies, PWL) were measured on post-surgery days 1, 3, and 7. The contralateral brain was obtained on post-surgery day 7 to determine the expressions of tumour necrosis factor (TNF-alpha), interleukin (IL)-1beta, IL-6, L-10, and nuclear factor-kappa B (NF-kappaB) activity. There were significant decreases in PPT and PWL after L5 spinal nerve transection (P < 0.001). Compared with the saline group, the rhEPO 3000 and 5000 U x kg(-1) groups resulted in significant increases in PPT and PWL (P < 0.001) and reduced the cerebral expressions of TNF-alpha, IL-1beta, IL-6, and NF-kappaB activity associated with the increase in IL-10 (rhEPO3000 group, P < 0.05, and rhEPO5000 group, P < 0.001, respectively). Administration of rhEPO 1000 U x kg(-1) had no significant effects on these variables. Preemptive rhEPO dose-dependently attenuated the mechanical and thermal hyperalgesia in L5 spinal nerve transection rats, which correlated with the decreased cerebral expressions of TNF-alpha, IL-1beta, and IL-6 via downregulating NF-kappaB activity and the increased expression of IL-10.