Antinociceptive interaction between opioids and medetomidine: systemic additivity and spinal synergy.

Abstract:

:The antinociceptive interaction on the tail flick (TF) and hot plate (HP) tests between opioid analgesics and medetomidine after intravenous (iv) or intrathecal administration were examined by isobolographic analysis. Male Sprague-Dawley rats received fixed ratios of medetomidine to morphine, fentanyl, and meperidine of 1:10 and 1:30, 10:1, and 1:3, respectively, by iv administration or 10:1, 3:1 and 10:1, and 1:3 by intrathecal administration, respectively. Data were expressed as the percentage maximal possible effect (%MPE). The A50 (dose producing 50% MPE) for each drug or drug combination was determined from the dose-response curve. Isobolographic analysis revealed that the effect of medetomidine combined with fentanyl, morphine, or meperidine was additive after iv administration. The intrathecal administration of combinations of medetomidine with the opioids produced a synergistic antinociceptive effect in the TF but not HP test. These data confirmed that the interaction between medetomidine and opioids in producing antinociception may be additive or synergistic, depending on the route of administration, drug ratio administered, and level of processing of the nociceptive input (i.e., spinal vs. supraspinal). Moreover, these results were consistent with a spinal role for alpha-2 adrenoceptors in mediating antinociception. The authors suggest that the interaction between the opioid and alpha-2 adrenergic receptors occurs within the spinal cord.

journal_name

Anesthesiology

journal_title

Anesthesiology

authors

Ossipov MH,Harris S,Lloyd P,Messineo E,Lin BS,Bagley J

doi

10.1097/00000542-199012000-00022

subject

Has Abstract

pub_date

1990-12-01 00:00:00

pages

1227-35

issue

6

eissn

0003-3022

issn

1528-1175

journal_volume

73

pub_type

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