Department of Anesthesiology, Osaka University Medical School, Osaka, Japan.
J Pharm Pharmacol. 2010 Dec;62(12):1760-7. doi: 10.1111/j.2042-7158.2010.01192.x. Epub 2010 Oct 5.
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.
据报道，鞘内给予 α2 肾上腺素能受体（α2AR）激动剂的效果在对全身吗啡慢性耐受的小鼠中增强。然而，尚未确定促成因素。在这里，我们研究了重复给予全身吗啡是否会影响鞘内给予右美托咪定的镇痛效力以及 A、B 和 C 型 α2AR（α2A、α2B 和 α2C AR）在小鼠背根神经节和背角中的表达。
在两周皮下注射吗啡或生理盐水后，鞘内给予右美托咪定以评估其镇痛作用。此外，使用 PCR 定量测定腰椎背根神经节中 α2AR 亚型和 μ 阿片受体 mRNA 的表达，并用免疫组织化学法检查腰椎背根神经节和背角中的 α2A 和 α2C AR。
每日吗啡增强了鞘内给予右美托咪定的镇痛作用，增加了所有 α2AR 亚型，但降低了背根神经节中 μ 阿片受体 mRNA 的表达，并增加了背根神经节和背角中 α2A 和 α2C AR 的免疫反应性。
这些结果表明，全身每日吗啡通过上调腰椎背根神经节和背角中的 α2A、α2B 和 α2C AR 增强了鞘内给予右美托咪定的镇痛效果。
