Recombinant human erythropoietin counteracts cisplatin-induced visceral hyperalgesia.
OBJECTIVE
Cisplatin exerts its cytotoxic effect through distinct DNA lesions, leading to peripheral neuropathy. The risk of sensory neuropathy is a common problem during cancer treatment with cisplatin, leading to somatic hyperalgesia. Yet, data focussing on cisplatin-induced impairment of the autonomic nervous system are limited. The present study was aimed to investigate the effect of recombinant human erythropoietin (rhEPO) on cisplatin-induced visceral hyperalgesia.


METHODS
C57BL/6 mice were treated either with cisplatin (2 mg/kg, once per week) or with cisplatin (2 mg/kg, once per week) plus rhEPO (40 microg/kg, 3 times per week) for 8 weeks. Controls were treated with saline. To quantify the visceromotor response (VMR) at week 9, standardized electrodes were implanted into the external oblique musculature for electromyographic recordings. After that, animals were decapitated and dorsal root ganglia (DRG) was removed for transmission electron microscopy studies.


RESULTS
Cisplatin-treated mice showed a significant increase of VMR compared to the controls [(7080 +/- 969) vs (2864 +/- 279); P< 0.001], while rhEPO dramatically counteracted this effect [(2962 +/- 336) vs (7080 +/- 969); P< 0.001)]. Transmission electron microscopy revealed cisplatin-induced structural lesions of nuclear membrane in DRG cells, which could be ameliorated by rhEPO.


CONCLUSIONS
Erythropoietin can significantly ameliorate the cisplatin-induced visceral hyperplasia and DRG nuclear membrane structure damage in mice, indicating a neuroprotective role of erythropoietin.
Yoon
Min-Suk
MS
Department of Neurology, University of Duisburg-Essen, Essen, Germany. Min-Suk.Yoon@uni-due.de
Bechmann
Lars
L
Obermann
Mark
M
Yepnjouo
Olivia
O
Egensperger
Rupert
R
Gerken
Guido
G
Katsarava
Zaza
Z
Thomale
Juergen
J
Holtmann
Gerald
G
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002945:Cisplatin; D003106:Colon / Q000294:innervation; D004195:Disease Models, Animal; D004576:Electromyography / Q000379:methods; D004921:Erythropoietin / Q000627:therapeutic use*; D005727:Ganglia, Spinal / Q000473:pathology; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission / Q000379:methods; D010812:Physical Stimulation / Q000379:methods; D011897:Random Allocation; D011994:Recombinant Proteins; D012007:Rectum / Q000294:innervation; D011984:Sensory Receptor Cells / Q000473:pathology / Q000648:ultrastructure; D014781:Viscera / Q000294:innervation*
D011994:Recombinant Proteins; D004921:Erythropoietin; D002945:Cisplatin