Figure 5.
Reversal of the SNL-induced increase in neuronal excitability and responsiveness by blockade of CaV1.2 expression. A, In vivo extracellular recording of the discharge pattern (lower trace) and firing frequency (upper trace) of a deep WDR neuron, in response to physiological innocuous (brush, pressure) and noxious (pinch) stimulation of its receptive field on the foot-paw (control animal). B, Mean spontaneous discharge frequency in sham and SNL animals and in rats intrathecally injected with anti-CaV1.2, anti-CaV1.3, and mismatch TP10-PNAs. In the SNL animals, spontaneous activity increased substantially, and was restored to normal by the specific blockade of CaV1.2 expression. Stars, p < 0.05. C, Mean neuronal responses to mechanical stimulation of the paw with von Frey hairs of increasing forces (5 and 10 g, innocuous; 25 and 50 g, noxious) in sham (filled symbols) and SNL animals (open symbols). Neuronal responses to natural stimulation were increased in SNL animals whatever the force. Three stars, p < 0.001, sham versus SNL. D, In SNL animals, normal responsiveness was restored by the specific blockade of CaV1.2 expression (filled circles), whereas the sensitization remained unchanged after application of anti-CaV1.3 (open circles) or mismatch TP10-PNAs (filled triangles). One star, p < 0.05; two stars, p < 0.01; three stars, p < 0.001 (“SNL + anti-CaV1.2” vs SNL). After anti-CaV1.2 TP10-PNA application, the responses were equivalent to the sham responses (p > 0.05). n, Number of recorded neurons. B–D were obtained from 8 sham, 26 SNL, 7 anti-CaV1.2 PNA-injected, 4 anti-CaV1.3 PNA-injected, and 6 mismatch PNA-injected rats.