Figure 1.

Schematic model of electric stimulation-induced paw flexion (a, EPF) and paw withdrawal (b, EPW) test in mice. (c) Frequency-specific stimulation of different sensory fibers is closely related to differential expression of voltage-dependent Na_v channels, which have distinct kinetics patterns during activation, inactivation, and recovery from inactivation or repriming. Because type I and II C-fibers are stimulated by LF-stimuli, nociceptive responses or p-ERK signals can be blocked by neonatal capsaicin pretreatment, or by NK1 and NMDA receptor anatgonists. Aδ- and Aβ-fibers, on the other hand, are stimulated by MF or HF stimuli, respectively. NMDA or non-NMDA receptor antagonists block spinal transmission caused by MF or HF-stimuli, respectively.