Activation of extracellular signal-regulated
protein kinases 5 in the spinal cord contributes
to the neuropathic pain behaviors induced by
CCI in rats
Lin Zhang*{{, Chun Xiao{, Jun-Ke Wang1, Li-Cai Zhang{ and Yin-Ming Zeng{
*
Published by Maney Publishing (c) W. S. Maney & Son Limited
Department of Anesthesia, The First Affiliated Hospital, Medical College of Qingdao University, Qingdao,
China
{
Jiangsu Key Laboratory of Anesthesiology, Jiangsu Institute of Anesthesiology, Xuzhou, China
{
Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical
School, Boston, MA, USA
1
Department of Anesthesia, The First Affiliated Hospital, China Medical University, Shenyang, China
Objective: To investigate whether activation and translocation of extracellular signal-regulated
kinase 5 (ERK5) is involved in the induction and maintenance of neuropathic pain and observe
the effects of activation and translocation of ERK5 on the expression of phosphorylated cAMP
response element binding (pCREB) in the chronic neuropathic pain.
Methods: Lumbar intrathecal catheters were chronically implanted in male Sprague–Dawley
rats. The left sciatic nerve was loosely ligated proximal to the sciatica’s trifurcation at y1.0 mm
intervals with 4-0 silk sutures. The phosphorothioate-modified antisense oligonucleotides (ASODNs) were intrathecally administered every 12 hours, 1 day pre-chronic constriction injury
(CCI) and 3 day post-CCI. Thermal and mechanical nociceptive thresholds were assessed with
the paw withdrawal latency to a radiant heat and von Frey filaments. Expressions of
phosphorylated ERK5 (pERK5), pCREB, were assessed by both Western blotting and
immunohistochemical analysis.
Results: Intrathecal injection of ERK5 AS-ODN significantly attenuated CCI-induced mechanical
allodynia and thermal hyperalgesia. CCI significantly increased the expression of pERK5 neurons
in the ipsilateral spinal dorsal horn to injury, not...