Intrathecal opioids block a spinal action of substance P in mice: Functional importance of both μ- and δ-receptors

Inhibition of intrathecal substance P-elicited behavior by μ-, δ- and κ-opioids was compared. In both the substance P behavioral test and the tail flick antinociceptive test, intrathecal [D-Ala²,Met⁵]enkephalinamide and [D-Ala², D-Leu⁵]enkephalin (DADL) were equipotent, morphine and ethylketazocine were less potent, but nalorphine was inactive. A long-lasting, highly selective, μ-receptor antagonist, β-funaltrexamine, blocked the inhibition of substance P behaviors by both morphine and ethylketazocine, but did not block the effect of DADL. These results suggest that spinal postsynaptic modulation of nociception is mediated by both δ-type and μ-type opioid agonists.