ISSLS prize winner: Erythropoietin inhibits spinal neuronal apoptosis and pain following nerve root crush

Yasufumi Sekiguchi, Shinichi Kikuchi, Robert R Myers, W Marie Campana
Spine 2003 December 1, 28 (23): 2577-84

STUDY DESIGN: The authors investigated the association of L5 proximal nerve root injury with spinal cord neuronal apoptosis (histologic) and whether exogenous erythropoietin therapy might reduce apoptosis/or pain (behavioral).

OBJECTIVES: The first objective was to determine whether nerve root crush induces specific programmed cell death of spinal neurons in the dorsal and ventral horn and whether this is correlated with pain behaviors. The second objective was to determine if exogenous erythropoietin might reduce apoptosis and/or pain.

SUMMARY OF BACKGROUND DATA: Whether spinal neuronal apoptosis is correlated with pain behaviors following nerve root injury remains unknown. It has been hypothesized that neuroprotective factors may alleviate pain behaviors by protecting neurons from death. Erythropoietin is a hematopoietic growth factor that recently has been demonstrated as a potent neuroprotective factor against ischemic damage in the brain. The effects of erythropoietin on pain and spinal cord neurons have not been examined.

METHODS: Sprague-Dawley rats received a L5 proximal nerve root crush injury or sham operation and were separated into two treatment groups for subcutaneous injection: 1) vehicle; 2) recombinant human erythropoietin, 2680 U/kg. The rats were sacrificed, and spinal cords were removed for apoptotic and immunohistochemical analysis at 0, 1, and 3 days after surgery. To determine whether recombinant human erythropoietin prevented mechanical allodynia in animals with nerve root crushes (n = 12/group), both treatment groups were tested for pain behaviors using the von Frey test at -1, -2, -3, 1, 3, 7, 11, and 14 days after surgery.

RESULTS: After nerve root injury, apoptotic neurons increased by 80% in the ipsilateral spinal cord and moderately in contralateral spinal cord in vehicle-treated animals compared to uninjured controls. Recombinant human erythropoietin reduced (P < 0.05) neuronal apoptosis in both superficial dorsal and ventral horns of the spinal cord. This corresponded with identification of erythropoietin and its receptors on spinal neurons and reductions in TNF-alpha colocalization in ventral horn neurons. Mechanical allodynia developed in the corresponding ipsilateral hind paw within 1 day and was sustained until day 14. Recombinant human erythropoietin-treated animals demonstrated faster recovery from mechanical allodynia compared with vehicle-treated controls (P < 0.05).

CONCLUSIONS: Our findings indicated that L5 proximal nerve root crush increased neuronal apoptosis in the superficial dorsal and ventral horn that correlated with mechanical allodynia. Exogenous recombinant human erythropoietin facilitated receptor-mediated neuroprotection of spinal cord neurons and faster recovery from mechanical allodynia. Erythropoietin may be a potential therapeutic factor for patients with low back pain by providing pain relief and neuroprotection.


You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Available on the App Store

Available on the Play Store
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"