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Antinociceptive effect of paeoniflorin via spinal α 2 ‐adrenoceptor activation in diabetic mice
Author(s) -
Lee Keiko K.,
Omiya Yuji,
Yuzurihara Mitsutoshi,
Kase Yoshio,
Kobayashi Hiroyuki
Publication year - 2011
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1016/j.ejpain.2011.04.011
Subject(s) - paeoniflorin , yohimbine , nociception , pharmacology , radix (gastropod) , antagonist , chemistry , medicine , receptor , chromatography , high performance liquid chromatography , biology , botany
Background: Shakuyakukanzoto (SKT) has been shown to modulate nociception in streptozotocin‐induced diabetic mice via selective activation of the descending noradrenergic systems. However, the active components of SKT that exert the analgesic effect remain unknown. Here, we administered Glycyrrhizae radix ( G. radix ), Paeoniae radix ( P. radix ), and the two active constituents of P. radix , paeoniflorin and albiflorin, to determine the components that stimulate spinal α 2 ‐adrenoceptors by promoting noradrenaline release. Methods: The two SKT components were separately administered to diabetic and non‐diabetic mice. A tail‐pressure test was used to determine the nociceptive threshold between 0 and 3 h after oral dosing. The time‐course profiles of the nociceptive threshold (g) and the area under the time response curve (AUC) were evaluated. Yohimbine, an α 2 ‐adrenoceptor antagonist, was intrathecally injected 15 min after paeoniflorin administration. Results: P. radix and G. radix did not induce significant antinociception in non‐diabetic mice. However, P. radix (250, 500 mg/kg) dose‐dependently and significantly increased the nociceptive threshold in diabetic mice between 0.5 and 2 h after administration, whereas all the tested doses of G. radix did not increase the nociceptive threshold. Both paeoniflorin (30 mg/kg) and albiflorin (10 mg/kg) significantly elevated the nociceptive threshold between 0.5 and 3 h and between 0.5 and 1 h after administration, respectively. The antinociceptive effect of paeoniflorin (30 mg/kg) was completely abolished by yohimbine. Conclusion: Our findings suggest that paeoniflorin is the key antinociceptive component in SKT that increases noradrenaline release and activates α 2 ‐adrenoceptors to modulate spinal nociceptive transmission in diabetic neuropathy.