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Figure 1.

Effects of i.c.v. administration of β-FNA (10 nmol), nor-BNI (10 nmol) and naltrindole (10 nmol) on the EM-1 (7.5 nmol i.c.v.) (A) or EM-2 (7.5 nmol i.c.v.) (B) induced central antinociception in mouse tail-flick test.

Data are expressed as differences in AUC between endomorphins (7.5 nmol) and endomorphins co-injected with β-FNA, nor-BNI or NTI during 0–30 min. Each value represents mean ± S.E.M. (n = 7–12 mice/group). ***p<0.001 indicating significant differences compared to Saline + Saline-injected group, ###p<0.001 indicating significant differences compared to Saline + endomorphins-injected group.

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Figure 1 Expand

Figure 2.

Dose-related effects of i.c.v. administration of NPFF on the central antinociception of EM-1 (i.c.v.) (A) and EM-2 (i.c.v.) (B), in mouse tail-flick assays.

(A) NPFF (3, 10 and 15 nmol) reduced 7.5 nmol EM-1-induced central antinociception. (B) NPFF (3, 10 and 15 nmol) potentiated 7.5 nmol EM-2-induced central antinociception. Each value represents mean ± S.E.M. (n = 7–12 mice/group). ***p<0.001 indicating significant differences compared to Saline + endomorphins - injected group.

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Figure 2 Expand

Figure 3.

Co-administrated RF9 (15 nmol, i.c.v.) antagonized the modulatory effects of NPFF (15 nmol, i.c.v.) on EM-1 and EM-2-induced central antinociception in mouse tail-flick test.

Data are expressed as differences in AUC between endomorphins (7.5 nmol) and endomorphins co-injected with NPFF, RF9 or agonists plus RF9 during 0–30 min. Each value represents mean ± S.E.M. (n = 7–8 mice/group). ***P<0.001 indicating significant differences compared to Saline + endomorphins - injected group; ###P<0.001 indicating significant differences from the modulatory effects of NPFF in the absence of RF9.

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Figure 3 Expand

Figure 4.

Dose-related effects of i.c.v. administration of NPFF receptors selective agonists on EM-1 (i.c.v.) induced central antinociception in mouse tail-flick test.

(A) NPVF (3, 10 and 15 nmol) potentiated EM-1(7.5 nmol) induced central antinociception. (B) dNPA (3, 10 and 15 nmol) reduced EM-1 (7.5 nmol) induced central antinociception. (C) Co-administration of RF9 (15 nmol, i.c.v.) antagonized the effects of NPFF (15 nmol, i.c.v.) on EM-1-induced central antinociception in mouse tail-flick test. Each value represents mean ± S.E.M. (n = 7–8 mice/group). ***P<0.001 indicating significant differences compared to Saline + EM-1-injected group. ###P<0.001 indicating significant differences from the modulatory effects of NPFF in the absence of RF9.

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Figure 4 Expand

Figure 5.

Dose-related effects of i.c.v. administration of NPFF receptor selective agonists on the EM-2 (i.c.v.) induced central antinociception in mouse tail-flick assays.

(A) NPVF (3, 10 and 15 nmol) and (B) dNPA (3, 10 and 15 nmol) potentiated EM-1(7.5 nmol) induced central antinociception. (C) Co-administration of RF9 (15 nmol, i.c.v.) antagonized the effects of NPFF (15 nmol, i.c.v.) on EM-2-induced central antinociception in mouse tail-flick test. Each value represents mean ± S.E.M. (n = 7–8 mice/group). ***P<0.001 indicating significant differences compared to Saline + EM-2-injected group. ###P<0.001 indicating significant differences from the modulatory effects of NPFF-related peptides in the absence of RF9.

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Figure 5 Expand

Figure 6.

The effects of i.c.v. administration of NPFF and related pepetides on the central antinociception of DAMGO (i.c.v.) in mouse tail-flick test.

(A) Dose-related effects of NPFF (3, 10 and 15 nmol) on the central antinociception of DAMGO. (B) Co-administrated RF9 (15 nmol, i.c.v.) antagonized the modulatory effects of NPFF (15 nmol, i.c.v.) on the central antinociception of DAMGO in mouse tail-flick test. (C) The effects of NPVF and dNPA on the central antinociception of DAMGO. Each value represents mean ± S.E.M. (n = 7–8 mice/group). **P<0.01 and ***P<0.001 indicating significant differences compared to Saline + DAMGO-injected group; ###P<0.001 indicating significant differences from the modulatory effects of NPFF in the absence of RF9.

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Figure 6 Expand

Figure 7.

The effects of i.c.v. administration of NPFF and related peptides on the central antinociception of U69593 (i.c.v.) in mouse tail-flick test.

(A) Dose-related effects of NPFF (3, 10 and 15 nmol) on the central antinociception of U69593. (B) Co-administrated RF9 (15 nmol, i.c.v.) antagonized the modulatory effects of NPFF (15 nmol, i.c.v.) on the central antinociception of U69593 (i.c.v.). (C) The effects of NPVF and dNPA on the central antinociception of U69593. Each value represents mean ± S.E.M. (n = 7–8 mice/group). ***P<0.001 indicating significant differences compared to Saline + U69593-injected group; ###P<0.001 indicating significant differences from the modulatory effects of NPFF in the absence of RF9.

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Figure 7 Expand