Nociceptors are interleukin-1beta sensors - PubMed (original) (raw)

IL-1β modulates activity of DRG neurons via p38 MAPK. A, Increase in phosphorylated p38 MAP kinase (pp38) in cultured DRG neurons after IL-1β (1 ng/ml, 10 min) demonstrated by immunocytochemistry and Western blot. B–E, Preincubation of DRG neurons for 40 min with the p38 inhibitor SB203580 (10 μ

m

) prevented the IL-1β mediated increases in excitability. C, Dose dependent effect of SB203580 on IL-1β-mediated decrease of spike threshold. (□, 10 μ

m

; ○, 100 n

m

; ▵, 10 n

m

). Arrow indicates time of application of IL-1β. Time point “-5” refers to data collected before application. Note no change in spike threshold after preincubation with 10 μ

m

SB203580 and significant decrease of threshold after preincubation with 10 n

m

SB203580. D, SB203580 (10 μ

m

) prevents IL-1β -mediated changes in numbers of spikes per stimulus (mean ± SEM) expressed as multiples of the rheobase for each recorded cell (n = 10). E, Ramp (333 pA/s) activated trains of action potentials showed no change in threshold after IL-1β in presence of SB203580 (10 μ

m

), but still demonstrated reduced spike adaptation. F, The ratio of the mean peak total and TTX-r sodium current amplitude (IL-1β, 20 min/control) (n = 10) showed no change after IL-1β in cells preincubated with 10 μ

m

SB203580 but increased significantly in presence of 10 n

m

SB203580. G, Quasi-steady-state current– voltage curves during a slow (35 mV/s) ramp demonstrating that SB203580 (10 μ

m

) blocked the IL-1β -mediated change in both early (amplitudeVehicle 148 ± 34 pA vs 151 ± 42 pA, p = 0.23; current activation onsetVehicle −53 ± 8 mV vs −36 ± 9 mV, p = 0.21; and peakVehicle −42 ± 8 mV vs −45 ± 10 mV, p = 0.11, n = 10) and late components (amplitudeVehicle 112 ± 25 pA vs 105 ± 12 pA, p = 0.1; current activation onsetVehicle −23 ± 6 mV vs −24 ± 4 mV, p = 0.09 and peakVehicle −12 ± 5 mV vs −16 ± 5 mV, p = 0.26, n = 10) of resulting inward current. Recordings for B–E were made using extracellular solution 4, those for F, solution 1, and those for G, solution 3 (Table 1).