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- W2007189893 abstract "In this report, we demonstrated that peripheral application of very low dose (amol ranges) of morphine induced flexor response through a substance P (SP) release at the nociceptor endings in mice. The intraplantar (i.pl.) application of morphine produced flexor response in a dose-dependent manner from 0.1 to 1000 amol. The μ-opioid receptor (MOP-R) agonist [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) also produced dose-dependent flexor response in same dose ranges. Morphine-induced flexor responses were markedly inhibited by naloxone and d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr amide (CTOP) both MOP-R antagonists and by intrathecal injection of antisense oligodeoxynucleotide (AS-ODN) for MOP-R which is expected to reduce the receptor expression in sensory nerve endings. Prior incubation with capsaicin, a depletor of SP from polymodal C fibers and [(+)-(2S,3S)-(2-methoxybenzylamino)-2-phenylpiperidine] (CP-99994), a tachykinin 1 receptor antagonist, also blocked the morphine-induced flexor responses. Moreover, pertussis toxin (PTX) which inactivates Gαi/o; [(1-[6-([(17b)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino)hexyl]-1H-pyrrole-2,5-dione)] (U-73122), an inhibitor of phospholipase C (PLC); ethyleneglycol-bis(β-aminoethyl ether) N,N,N′,N′-tetraacetic acid (EGTA), a Ca2+ chelating agent; xestospongin C, a membrane-permeable inositol trisphosphate (InsP3) receptor antagonist inhibited the morphine-flexor responses. However, thapsigargin, a depletor of intracellular Ca2+ concentration and diphenhydramine, a histamine (His) H1 receptor antagonist, were unable to block the morphine-induced flexor responses. These results suggest that extremely low doses of morphine can stimulate sensory nerve endings through activation of peripheral MOP-R and its downstream mechanisms include activation of PLC through a SP release from polymodal C fibers." @default.
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- W2007189893 date "2002-12-01" @default.
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- W2007189893 title "Stimulation of peripheral nociceptor endings by low dose morphine and its signaling mechanism" @default.
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- W2007189893 doi "https://doi.org/10.1016/s0197-0186(02)00047-5" @default.
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