Interaction between intrathecal morphine and glutamate receptor antagonists in formalin test.

Abstract:

:The analgesic interaction between intrathecally administered morphine and the NMDA receptor antagonist, ((+/-)-2-amino-5-phosphonopentanoic acid; AP-5), the NMDA receptor glycine site antagonist, (5-nitro-6,7-dichloro-2,3-quinoxaline dion; ACEA 1021), or the AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor antagonist (ACEA 2752) in the formalin test was investigated with a rat model of chronic lumbar intrathecal catheterization. After obtaining dose-response curves for each agent, combinations of morphine and AP-5, ACEA 1021 or ACEA 2752 were tested for their effect on the number of flinches in the formalin test and for associated side-effects, such as motor disturbances, flaccidity, and agitation/allodynia. Using isobolographic analyses, a potent analgesic synergy was observed with decreased side-effects between morphine and ACEA 2752 or AP-5. ACEA 1021 increased the analgesic effect of low-dose morphine. Spinal mu-opioid receptor activation and NMDA or AMPA receptor antagonism showed a synergistic antinociception against tonic pain. These results suggest an important direction in the management of inflammatory pain.

journal_name

Eur J Pharmacol

authors

Nishiyama T

doi

10.1016/s0014-2999(00)00268-5

keywords:

subject

Has Abstract

pub_date

2000-05-03 00:00:00

pages

203-10

issue

3

eissn

0014-2999

issn

1879-0712

pii

S0014299900002685

journal_volume

395

pub_type

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