Figure 2.
Acute pain behavior and in vivo electrophysiology of wide dynamic range (WDR) in Dicer mutant mice. A, Rotarod studies showed no motor deficits in conditional Dicer-null animals (n = 12, WT; n = 20, KO). B, Acute mechanical pressure applied with the Randall–Selitto apparatus demonstrated identical behavior in KO and WT mice (n = 12, WT; n = 20, KO). C, Responses to low-threshold mechanical stimulation by Von Frey filaments are normal in the null mutants (n = 8, WT; n = 15, KO). D, Hargreaves' apparatus demonstrates identical latencies of response to thermal stimulation (n = 8, WT: n = 16, KO). E, Supra-spinal reflexes to heat (50 and 55°C) using the hot plate apparatus demonstrates identical latencies in KO and WT mice (n = 9, WT; n = 14, KO). F, Cold behavior (number of liftings) is reduced in the Dicer-null mutant mice (0°C) using the cold plate apparatus (n = 16, WT; n = 22, KO). G, A-fiber and C-fiber firing thresholds of WDR neurons in control Nav1.8Cre+/− mice (black) (n = 14) and Dicer KO mice (white) (n = 16). H, Responses to transcutaneous electrical stimulation of the receptive field (a train of 16 2-ms-wide electrical pulses at 0.5 Hz at 3× C-fiber threshold). Spikes evoked between 0 and 50 ms were classified as evoked by A-fiber input, and those evoked between 50 and 250 ms were classified as evoked by C-fiber input. Postdischarge (PD) describes the spikes that are evoked between 250 and 800 ms and correlate with C-fiber activity. Input is determined by the first stimulus of the train × 16 and reflects nonpotentiated C-fiber-evoked WDR neuron responses. Wind-up (WU) is determined by calculating additional spikes above the predicted constant baseline response and describes the increased neuronal excitability evoked by C-fibers to repeated constant stimulation. C-fiber activity, wind-up, and postdischarge were all significantly decreased in diphtheria toxin A chain (DTA) mice. I, Evoked responses from innocuous dynamic brush, noxious pinch, and a cold (1°C) water jet stimulus. J, Evoked responses from Nav1.8 Cre+/− mice (solid line) and Dicer−/− mice (dashed line) to graded von Frey filaments. K, Thermally evoked responses using water jets at graded temperatures (Temp). There was no significant difference between the two groups.