Farnesyl pyrophosphate is a novel pain-producing molecule via specific activation of TRPV3 - PubMed (original) (raw)

FPP reduces TRPV3 thermal threshold leading to heightened heat sensitivity. A, summary of the changes in the paw withdrawal latencies from Hargreaves tests with or without FPP treatment. Hargreaves latencies were decreased by 42.3 ± 9.5% for wild-type mice, by 36.2 ± 3.5% for TRPV1-null mice and by 43.2 ± 5.2% for mice treated with scrambled shRNA (SC). No significant decrease in the latencies was detected in mice pretreated with mTRPV3-shRNA. The Hargreaves latencies were examined 30 min after the hind paw intradermal administration of FPP (1 m

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in 10 μl). n = 10 for each histogram (*, p < 0.05; **, p < 0.01, Student's t test). B, representative heat-induced current responses of TRPV3-transfected HEK293T cells. When temperature elevated, the TRPV3-mediated currents were elicited (top: 10 n

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FPP was incubated; bottom: without FPP incubation). C, summary of the changes in the heat thresholds of TRPV3 in experiments of B. The mean heat threshold of TRPV3 from the group without FPP incubation was 31.8 ± 0.8 °C (n = 7), and the value from the group with FPP incubation was 28.8 ± 0.5 °C (n = 8). D, summary of the Q10 values of the heat-sensitive phases of TRPV3 activation in experiments of B. The mean Q10 with or without FPP incubation was 16.5 ± 5.4 and 21.9 ± 9.7, respectively. No statistical difference was found. E, summary of the peak TRPV3 current densities activated by heat, FPP, or heat plus FPP at ± 60 mV (n = 8 with heat alone, n = 6 with 10 n

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FPP, n = 7 with heat plus 10 n

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FPP, n = 12 with 100 n

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FPP, n = 5 with heat plus 100 n

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FPP, n = 7 with 1 μ

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FPP, and n = 17 with heat plus 1 μ

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FPP. Filled bars for current densities at −60 mV, and open bars at + 60mV). TRPV3-transfected HEK293T cells were used. Dotted lines indicate the average peak currents activated by heat alone. F, average peak inward tail currents at −120 mV from the step protocol as shown in Fig. 2_C_ were plotted by a function of test voltage steps (n = 10 with 10 n

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FPP (open circles), n = 8 with heat (36 °C) plus 10 n

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FPP (closed circles), n = 8 with heat plus 100 n

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FPP (gray triangles), n = 5 with heat plus 1 μ

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FPP (open triangles), and n = 9 without stimulation (gray circles)). Symbols represent the data collected from every 20 mV. The curves were fitted by Boltzmann equation. V½ was 143 mV at the resting state, 116 mV during 10 n

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FPP, 30 mV during heat plus 10 n

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FPP, −27 mV during heat plus 100 n

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FPP, and −122 mV during heat plus 1 μ

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FPP applications. *, p < 0.05; **, p < 0.01, Student's t test.