Role of spinal MCP-1-ERK-KIF17∕NR2B signaling pathway in maintenance of type 2 diabetic neuro-pathic pain in rats / 中华麻醉学杂志

ABSTRACT

Objective To explore the role of spinal monocyte chemoattractant protein?1 ( MCP?1) ?extracellular signal?regulated protein kinase ( ERK)?kinesin superfamily motor protein 17 ( KIF17)∕N?methyl?D?aspartate receptor subunit 2B ( NR2B) signaling pathway in the maintenance of type 2 diabetic neuropathic pain (DNP) in rats. Methods Type 2 diabetes mellitus was induced by a high?fat and high?sucrose diet and intraperitoneal streptozotocin ( STZ) 35 mg∕kg, and confirmed by fasting blood glucose level≥16?7 mmol∕L 3 days later in male Sprague?Dawley rats aged 6 weeks. Type 2 DNP was confirmed when the mechanical paw withdrawal threshold ( MWT ) and thermal paw withdrawl latency ( TWL ) measured on day 14 after STZ administration decreased to< 80% of the baseline value. The rats with type 2 DNP were randomly divided into 4 groups ( n=36 each) using a random number table: type 2 DNP group (group DNP), type 2 DNP +MCP?1 neutralizing antibody group (group DM), type 2 DNP +ERK inhibi?tor group (group DE) and type 2 DNP + dimethyl sulfoxide group ( group DD). In DM, DE and DD groups, 0?1 ng∕μl MCP?1 neutralizing antibody 10 μl, 0?5 μg∕μl U0126 10 μl and 5 % dimethyl sulfoxide 10 μl were injected intrathecally, respectively, once a day for 14 consecutive days starting from 14 days after administration of STZ. Another 36 normal rats fed a common forage diet were adopted as con?trol group ( group C) . MWT and TWL were measured before STZ injection and at 1, 3, 7 and 14 days after STZ injection ( T0-4 ) . Nine rats were sacrificed after measurement of pain thresholds at T1-4 , and the lumbar segments ( L4-6 ) of the spinal cord were removed for determination of the expression of phosphoryla?ted ERK (p?ERK), KIF17 and phosphorylated NR2B (p?NR2B) by Western blot. Results Compared with group C, the MWT was significantly decreased, the TWL was shortened, and the expression of p?ERK, KIF17 and p?NR2B was up?regulated at T1-4 in DNP, DM, DE and DD groups. Compared with group DNP, the MWT at T3-4 in group DM and at T2-4 in group DE was significantly increased, the TWL at T3-4 in group DM and at T2-4 in group DE was prolonged, and the expression of p?ERK, KIF17 and p?NR2B was down?regulated at T2-4 in DM and DE groups, and no significant changes were found in the pa?rameters mentioned above in group DD. Conclusion Spinal MCP?1?ERK?KIF17∕NR2B signaling pathway is involved in the maintenance of type 2 DNP in rats.