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.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Anesthesiology, Osaka University Medical School, Osaka, Japan.
Shinji
S
Tamagaki
Takahiro
T
Suzuki
Satoshi
S
Hagihira
Yukio
Y
Hayashi
Takashi
T
Mashimo
D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D020927:Dexmedetomidine / Q000008:administration & dosage* / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000008:administration & dosage* / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D020671:Posterior Horn Cells / Q000187:drug effects*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D058647:Adrenergic alpha-2 Receptor Agonists; D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D018341:Receptors, Adrenergic, alpha-2; D020927:Dexmedetomidine; D009020:Morphine