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

作者：Tamagaki Shinji; Suzuki Takahiro^*; Hagihira Satoshi; Hayashi Yukio; Mashimo Takashi

来源：Journal of Pharmacy and Pharmacology, 2010, 62(12): 1760-1767.

DOI：10.1111/j.2042-7158.2010.01192.x

• alpha2 adrenergic receptor
• dexmedetomidine
• dorsal horn
• dorsal root ganglion
• morphine

Objectives It has been reported that the effect of intrathecally administered alpha 2 adrenergic receptor (alpha 2 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 alpha 2 AR (alpha 2A, alpha 2B and alpha 2C AR) in the dorsal root ganglion and dorsal horn in mice.
Methods After subcutaneous injection of morphine or saline for two weeks, dexmedetomidine was administered intrathecally to evaluate its antinociceptive effect. Also, the alpha 2 AR subtypes and mu-opioid receptor mRNA expression in lumbar dorsal root ganglion was quantified using PCR, and alpha 2A and alpha 2C AR in lumbar dorsal root ganglion and dorsal horn were examined by immunohistochemistry.
Key findings Daily morphine enhanced the antinociceptive effect of intrathecal dexmedetomidine, increased all the alpha 2 AR subtypes but decreased the mu-opioid receptor mRNA expression in dorsal root ganglion and increased immunoreactivity of alpha 2A and alpha 2C AR in dorsal root ganglion and dorsal horn.
Conclusions These results suggest that systemic daily morphine enhances the analgesic effect of intrathecal dexmedetomidine via up-regulation of the alpha 2A, alpha 2B and alpha 2C AR in lumbar dorsal root ganglion and dorsal horn.

• 出版日期2010-12