Abstract: Objective To discuss the effects of intrathecal injection of minocycline on the expression of acid-sensing ion channel 1a (ASIC1a) in the spinal cord of rats with bone cancer pain (BCP). Methods Female SD rats weighting 180 to 220 g were randomly divided into four groups: a sham+normal saline group (group Ⅰ), a sham+minocycline group (group Ⅱ), a BCP+minocycline group (group Ⅲ) and a BCP+normal saline group (group Ⅳ). Free walk-associated pain was scored 1 day before modeling and 3, 5, 7, 10, 14 and 18 days after modeling, while paw withdrawal mechanical threshold (PWMT) after mechanical stimulus were determined(n=8). Meanwhile, 4 rats in each group were scarified randomly 1 day before modeling and 3, 5, 7, 10, 14 and 21 days after modeling. Their lumbar segments of the spinal cord were removed to determine the expression of ASIC1a by Western blotting. Furthermore, the cell with positive ASIC1a and ionized calcium binding adapter 1(Iba-1) expression in the dorsal horn was observed by immunofluoresence staining 1, 3, 7, 14 and 21 days after modeling(n=4). Results ① Compared with groups Ⅰand Ⅱ, PWMT in groups Ⅲ and Ⅳ was significantly decreased on day 5 after modeling (P<0.01), and remained at low levels on days 7 and 14 (P<0.01). Compared with groups Ⅰand Ⅱ, free walk?蛳associated pain scores in groups Ⅲ and Ⅳ were significantly increased on days 14 and 18 (P<0.01). Compared with group Ⅳ, PWMT in group Ⅲ were significantly increased on days 7, 10 and 14 after modeling (P<0.05). ② Compared with groups Ⅰand Ⅱ, the levels of ASIC1a in groups Ⅲ and Ⅳ were significantly increased from day 3 after modeling (P<0.01) and reached the peak from days 14 to 18(P<0.01). Compared with group Ⅳ, the level of ASIC1a in group Ⅲ was significantly decreased on days 5, 7, 10, 14 and 18 after modeling(P<0.05). ③ Compared with groups Ⅰand Ⅱ, the number of ASIC1a-positive cells and activated microglia were significantly increased in group Ⅲ and Ⅳ on days 3, 7, 14 and 21 after modeling(P<0.05), without double stained cells. Compared with group Ⅳ, the number of ASIC1a-positive cells and activated microglia were significantly decreased in group Ⅲ(P<0.01). Conclusions ASIC1a in the spinal cord may be involved in the formation and maintenance of BCP. Intrathecal injection of minocycline can relieve the mechanical pain in rats, which may be achieved by inhibiting the expression of ASIC1a in the spinal cord.
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