Effect of intrathecal TRESK gene recombinant adenovirus on activities of p38MAPK and ERK in spinal cord of rats with neuropathic pain

Abstract

Objective To evaluate the effects of intrathecal TRESK gene recombinant adenovirus on the expression of p38 mitogen-activated protein kinase (p38MAPK) and extracellular signal-regulated kinase(ERK) in the spinal cord of rats with neuropathic pain. Methods Thirty-six male Sprague-Dawley rats, weighing 200-250 g, were randomly divided into 6 groups (n= 6 each) using a random number table: control group (group C); sham operation group (group S); neuropathic pain group (group NP); TRESK overexpression adenovirus group (group TRESK); negative adenovirus group (group Virus); normal saline group (group NS). The rats underwent spared nerve injury (SNI) to establish the model of neuropathic pain.In TRESK, NS and Virus groups, pAd/CMV/V5-DEST-TRESK 25 μl (109 IU/ml), negative adenovirus 25 μl and normal saline 25 μl were intrathecally injected, respectively, immediately after SNI.At 1 day before SNI (baseline, T0) and 1, 3 and 7 days after SNI (T1-3), the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured.The rats were sacrificed after the last measurement of pain threshold at T3.The lumbar segments (L4, 5) of the spinal cord were removed for determination of phosphorylation of p38MAPK and ERK by Western blot. Results Compared with group C, the MWT was significantly decreased at T1-3, and the phosphorylation of p38MAPK and ERK was increased in NP, TRESK, Virus and NS groups.Compared with group NP, the MWT was significantly increased at T1-3, and the phosphorylation of p38MAPK and ERK was decreased in group TRESK, and no significant change was found in phosphorylation of p38MAPK and ERK in Virus and NS groups.There was no significant difference in TWL between the six groups. Conclusion Inhibited activities of p38MAPK and ERK in the spinal cord may be involved in the mechanism by which intrathecal TRESK gene recombinant adenovirus alleviates neuropathic pain in rats. Key words: Potassium channels; Transfection; Injections, spinal; p38 Mitogen-activated protein kinases; Extracellular signal-regulated MAP kinases; Neuralgia; Spinal cord