Relationship between G9a and Slack in spinal cord dorsal horn during remifentanil-induced hyperalgesia in a rat model of incisional pain

Abstract

Objective To evaluate the relationship between euchromatic histone-lysine N-methyltransferase (G9a) and sodium-dependent activation of potassium channel (Slack) in the spinal cord dorsal horn during remifentanil-induced hyperalgesia in a rat model of incisional pain. Methods Clean-grade healthy male Sprague-Dawley rats, aged 1 month, weighing 100-120 g, were divided into 4 groups (n=6 each) by a random number table method: normal saline group (S group), vector group (V group), vector plus remifentanil plus incisional pain group (VRI group), and G9a-siRNA plus remifentanil plus incisional pain group (DRI group). In VRI group and DRI group, vector 1 μl was injected into the L4-5 spinal dorsal horn, 3 days later remifentanil 1 μg·kg-1·min-1 was intravenously infused via the tail vein for 60 min, and the model of incisional pain was established simultaneously.The equal volume of normal saline was given instead in S and V groups.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before remifentanil infusion (T0) and 2, 6, 24 and 48 h after infusion (T1-4). Rats were sacrificed after behavioral tests, and the L4, 5 segments of spinal dorsal horns were taken for determination of the expression of G9a, H3K9me2 and Slack by Western blot. Results Compared with S group, TWL was significantly shortened, and MWT was decreased at T1-4, the expression of G9a and H3K9me2 was up-regulated, and the expression of Slack was down-regulated in VRI group (P<0.05). Compared with VRI group, the TWL was significantly prolonged and MWT was increased at T1-4, the expression of G9a and H3K9me2 was down-regulated, and Slack expression was up-regulated in DRI group (P<0.05). Conclusion The mechanism by which remifentanil induces hyperalgesia is related to up-regulating G9a and H3K9me2 expression and down-regulating Slack expression in the spinal dorsal horn of rats with incisional pain. Key words: Piperidines; Hyperalgesia; Spinal cord; Histone-lysine N-methyltransferase; Potassium channels