Role of T-type calcium channels in up-regulation of spinal CaMKII expression in rats with neuropathic pain

Objective To evaluate the role of T-type calcium channels in up-regulation of spinal Ca2+ /calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) expression in rats with neuropathic pain. Methods Forty-eight male Sprague-Dawley rats, weighing 230-270 g, in which intrathecal catheters were successfully implanted, were divided into 4 groups (n=12 each) using a random number table: sham operation group (group S), neuropathic pain group (group NP), normal saline group (group NS), and T-type calcium channel blocker mibefradil group (group M). The model of neuropathic pain was established by chronic compression of the dorsal root ganglion (DRG). Normal saline 20 μl and mibefradil 200 μg (diluted to 20 μl in normal saline) were injected intrathecally at 5 days after compression of the DRG in NS and M groups, respectively.Before intrathecal catheter implantation (T1), before compression of the DRG (T2), at 5 days after compression of the DRG and before intrathecal administration (T3), and at 30, 60, 120 and 240 min after intrathecal administration (T4-7), the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured.The rats were sacrificed after the last measurement of the pain threshold at T7, and the lumbar enlargement segments of the spinal cord were harvested for determination of CaMKⅡ expression by Western blot. Results Compared with group S, the MWT was significantly decreased, and TWL was significantly shortened at T3-7, and the expression of spinal CaMKⅡ was significantly up-regulated in NP and M groups (P 0.05). Conclusion T-type calcium channels are opened, the intracellular free calcium ion concentrations are increased, and activated spinal CaMKⅡ is involved in the development of neuropathic pain in rats. Key words: Calcium channels, T-Type; Neuralgia; Spinal cord; Calcium-calmodulin-dependent protein kinase type 2