Effect Of Intrathecal Dexmedetomidine Research Articles

Effect of intrathecal dexmedetomidine on acute inflammatory pain in mice

目的 探讨鞘内注射右美托咪啶对小鼠急性炎性痛的影响.方法 雄性成年昆明小鼠110只,体重18～20 g,采用随机数字表法,将其随机分为5组(n=22):二甲亚砜组(DMSO组)、炎性痛组(IP组)和不同剂量右美托咪啶组(D1-3组).D1-3组分别鞘内注射右美托咪啶0.100、0.020和0.004μg/μl(溶于10μl人工脑脊液中).于鞘内注射后5 min时,IP组和D1-3组左后爪底皮内注射辣椒素0.1 μg/μl(溶于10 μl二甲基亚砜中),制备小鼠急性炎性痛模型；DMSO组爪底注射二甲基亚砜10μ1.每组随机取8只小鼠,于爪底给药前1 h(T0)、给药后即刻(T1)、5 min(T2)和10 min(T3)时测定热缩爪潜伏期；每组随机取8只小鼠,记录5 min内出现舔/咬给药侧爪的时间.于爪底给药后5 min时,每组随机处死6只小鼠,取脊髓L4-5段,采用Western blot法测定磷酸化ERK1/2(p-ERK1/2)和ERK1/2的表达.结果 与DMSO组比较,IP组和D3组T1和T2时热缩爪潜伏期缩短,舔/咬爪时间延长,脊髓p-ERK1/2表达上调(P＜0.01),D1组和D2组T1-3时热缩爪潜伏期延长(P＜0.01),舔/咬爪时间和脊髓p-ERK1/2表达差异无统计学意义(P＞0.05)；与IP组和D3组比较,D1组和D2组T1～3时热缩爪潜伏期延长,舔/咬爪时间缩短,脊髓p-ERK1/2表达下调(P＜0.05)；IP组和D3组间、D1组和D2组间热缩爪潜伏期、舔/咬爪时间和脊髓p-ERK1/2表达比较差异无统计学意义,各组间脊髓ERK1/2表达比较差异无统计学意义(P＞0.05).结论 鞘内注射右美托咪啶可减轻小鼠急性炎性痛,其机制与抑制脊髓ERK1/2的活性有关。

Effect of intrathecal dexmedetomidine on expression of cAMP response element-Wnding protein phosphorylation in spinal dorsal horn in a rat model of bone cancer pain

Objective To investigate the effect of intrathecal (IT) dexmedetomidine on the expression of cAMP response element-binding protein phosphorylation (p-CREB) in spinal dorsal horn in a rat model of bone cancer pain. Methods Sixty-four adult female Wistar rats weighing 200-240 g were randomly divided into 4 groups (n = 16 each): sham operation group (group S); bone cancer pain group (group BP); normal saline group ( group NS) ; dexmedetomidine group (group D) . Bone cancer pain was induced by injecting Walker 2S6 mammary gland carcinoma cell suspension (2 ×106 cells/ml) 10μl into the medullary cavity of the tibia in BP, NS and D groups. Groups S and BP received no IT injection. Croups NS and D received IT injection of NS 10 μl and dexme detomidine 5 μg/kg respectively 7 days after successful establishment of the model. Ten animals were selected from each group at 1 day before IT administration (T0), immediately before IT administration (T1 ) and at 1, 6, 12 and 24 h after IT administration (T2-5 ) and paw withdrawal threshold (PWT) to mechanical stimuli was measured with von Frey filaments. The other 6 rats in each group were sacrificed at T4 and the spinal cord was removed for determination of p-CREB expression in the spinal dorsal horn.Results PWT was significantly decreased at T1-5 and pCREB expression up-regulated at T4 in BP, NS and D groups compared with group S ( P ＜ 0.05) . Compared with group BP, PWT was significantly decreased at T2-5 and p-CREB expression down-regulated at T4 in group D ( P ＜0.03), while no significant change in PWT and p-CREB expression was found in group NS (P ＞ 0.05) .Conclusion IT dexmedetomidine can reduce the bone cancer pain through inhibiting the phosphorylation of CREB in rat spinal dorsal horn. Key words: Dexmedetomidine; Bone neoplasms; Cyclic AMP response element-binding protein; Spinal cord

Systemic daily morphine enhances the analgesic effect of intrathecal dexmedetomidine via up-regulation of alpha 2 adrenergic receptor subtypes A, B and C in dorsal root ganglion and dorsal horn

It has been reported that the effect of intrathecally administered α2 adrenergic receptor (α2 AR) agonists is enhanced in mice that are chronically tolerant to systemic morphine. However, contributory factors have not been identified. Here we examined whether repeated systemic morphine affected the analgesic potency of intrathecal dexmedetomidine and the expression of subtype A, B and C α2 AR (α2A, α2B and α2C AR) in the dorsal root ganglion and dorsal horn in mice. After subcutaneous injection of morphine or saline for two weeks, dexmedetomidine was administered intrathecally to evaluate its antinociceptive effect. Also, the α2 AR subtypes and µ-opioid receptor mRNA expression in lumbar dorsal root ganglion was quantified using PCR, and α2A and α2C AR in lumbar dorsal root ganglion and dorsal horn were examined by immunohistochemistry. Daily morphine enhanced the antinociceptive effect of intrathecal dexmedetomidine, increased all the α2 AR subtypes but decreased the µ-opioid receptor mRNA expression in dorsal root ganglion and increased immunoreactivity of α2A and α2C AR in dorsal root ganglion and dorsal horn. These results suggest that systemic daily morphine enhances the analgesic effect of intrathecal dexmedetomidine via up-regulation of the α2A, α2B and α2C AR in lumbar dorsal root ganglion and dorsal horn.

Supraspinal Effects of Intrathecal Dexmedetomidine in Rats

Supraspinal Effects of Intrathecal Dexmedetomidine in Rats