• Shinji Tamagaki, Takahiro Suzuki, Satoshi Hagihira, Yukio Hayashi, and Takashi Mashimo.
• Department of Anesthesiology, Osaka University Medical School, Osaka, Japan.
• J. Pharm. Pharmacol. 2010 Dec 1;62(12):1760-7.

Objectives 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.MethodsAfter 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.Key FindingsDaily 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.ConclusionsThese 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.© 2010 The Authors. JPP © 2010 Royal Pharmaceutical Society of Great Britain.

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