Fig 1.
Effect of paclitaxel on mechanical hyperalgesia in mice.
Effect of a single administration of paclitaxel (2, 5 mg/kg, i.p.) on mechanical hyperalgesia in mice. The nociceptive threshold was determined by the von Frey filament test. Each point represents the mean ± S.E.M of 8 mice. **P < 0.01, ***P < 0.001 vs. respective 10% DMSO group.
Fig 2.
Effect of paclitaxel on the protein levels of spinal NFκB and pNFκB in mice.
Immunoblots of (A) NFκB and (B) pNFκB were normalized by GAPDH. The NFκB column represents the mean ± S.E.M of 5–7 mice. The pNFκB column represents the mean ± S.E.M of 3–5 mice. ** P < 0.01 vs. 10%DMSO group.
Fig 3.
Effect of the NFκB inhibitor, PDTC, on paclitaxel-induced mechanical hyperalgesia in mice.
(A) Time course of the effect of PDTC (100 ng/5μl, i.t.) on the mean mechanical threshold in paclitaxel-treated mice. (B) Effect of PDTC (100 ng/5μl, i.t.) on the mean mechanical threshold in paclitaxel-treated mice on day 3. PDTC was administered 30 minutes before the injection of paclitaxel (5 mg/kg, i.p.). The nociceptive threshold was determined by the von Frey filament test. Each point represents the mean ± S.E.M of 8–10 mice. ***P < 0.001 vs. saline-10%DMSO group. ###P < 0.001 vs. saline-paclitaxel group.
Fig 4.
Effect of pretreatment with RKT on paclitaxel (single injection)-induced mechanical hyperalgesia in mice.
(A) Time course of the effect of RKT (0.1, 0.3, 1 g/kg p.o.) on the mean mechanical threshold in paclitaxel-treated mice. (B) Effect of RKT (0.1, 0.3, 1 g/kg p.o.) on the mean mechanical threshold in paclitaxel-treated mice on day 3. RKT was administered 24 hours before the injection of paclitaxel (5 mg/kg, i.p.). RKT was administered 1 hour before each nociceptive test. The nociceptive threshold was determined by the von Frey filament test. Each point represents the mean ± S.E.M of 8–9 mice. *P < 0.05, ***P < 0.001 vs. 10%DMSO-DW group. ###P < 0.001 vs. paclitaxel-DW group.
Fig 5.
Effect of post-treatment with RKT on paclitaxel (single injection)-induced mechanical hyperalgesia in mice.
(A) Time course of the effect of RKT (1 g/kg, p.o.) on the mean mechanical threshold in paclitaxel-treated mice. (B) Effect of RKT (1 g/kg p.o.) on the mean mechanical threshold in paclitaxel-treated mice on day 2. RKT was administered 24 hours after the injection of paclitaxel (5 mg/kg, i.p.). RKT was administered 1 hour before each nociceptive test. The nociceptive threshold was determined by the von Frey filament test. Each point represents the mean ± S.E.M of 7–8 mice. ***P < 0.001 vs. 10%DMSO-DW group.
Fig 6.
Effect of RKT on paclitaxel (repeated injections)-induced mechanical hyperalgesia in mice.
RKT (1g/kg, p.o.) was administered before the injection of paclitaxel (2 mg/kg, i.p.) on days 1, 3, 5 and 7. RKT was administered 1 hour before each nociceptive test. The nociceptive threshold was determined by the von Frey filament test. Each point represents the mean ± S.E.M of 7–8 mice. *** P < 0.001 vs. 10%DMSO-DW group. ##P < 0.01 vs. paclitaxel-DW group.
Fig 7.
Effect of [D-Lys3]-GHRP-6 on the antihyperalgesic effect of RKT against paclitaxel-induced mechanical hyperalgesia in mice.
(A) Time course of the effect of [D-Lys3]-GHRP-6 (10 mg/kg, i.p.) on the antihyperalgesic effect of RKT (1 g/kg, p.o.) on the mean mechanical threshold in paclitaxel-treated mice. (B) Effect of [D-Lys3]-GHRP-6 (10 mg/kg, i.p.) on the antihyperalgesic effect of RKT (1 g/kg, p.o.) on the mean mechanical threshold in paclitaxel-treated mice on day 3. Paclitaxel (5 mg/kg, i.p.) and RKT (1 g/kg, p.o.) were injected once a day for 3 days. [D-Lys3]-GHRP-6 (10mg/kg, i.p.) was injected on day 2, 15 min before the administration of RKT. RKT was administered 1 hour before each nociceptive test. The nociceptive threshold was determined by the von Frey filament test. Each point represents the mean ± S.E.M of 6–8 mice. ***P < 0.001 vs saline-DW-paclitaxel group, ###P < 0.001 vs saline-RKT-paclitaxel group.
Fig 8.
Effect of RKT on the protein levels of spinal NFκB and pNFκB in mice treated with paclitaxel.
Immunoblots of (A) NFκB and (B) pNFκB were normalized by GAPDH. The NFκB column represents the mean ± S.E.M of 5–7 mice. The pNFκB column represents the mean ± S.E.M of 3–5 mice. **P < 0.01 vs. 10%DMSO-DW group. #P < 0.05 vs. paclitaxel-DW group.