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In the present study, we asked whether multiple intrathecal injections of deltorphin II, a selective delta opioid receptor (DOPR) agonist, induced DOPR tolerance in three behavioral assays. Unilateral inflammation caused by complete Freund's adjuvant (CFA) injection into the rat or mouse hind paw (CFA model) induced thermal hyperalgesic response that was transiently and dose-dependently reduced by intrathecal administration of deltorphin II or morphine. In both rodent species, the effect of deltorphin II was not modified by a single prior administration of deltorphin II, suggesting an absence of acute tolerance in this paradigm. Repeated administration of intrathecal deltorphin II or s.c. SB-235863 (five consecutive injections over 60 h) also failed to impair the antihyperalgesic response to delta opioid receptor agonist, whereas repeated intrathecal or s.c. injections of morphine induced a significant decrease in the …