Transformation of pressure- and heat-induced discharges of feline cutaneous C-fiber mechano-heat-sensitive units by lidocaine and N-propylajmaline

Abstract

Subcutaneous lidocaine (0.1%) and N-propylajmaline (NPA, 0.01%), inhibited pressure- and heat-evoked discharges in feline cutaneous C-fiber mechano-heat-sensitive (CMH) units. Initial suppression of discharges was followed by the period of resting and use-dependent (UD) inhibition, evaluated with double thermal (50 °C, 10 s) or triple mechanical (0.5 N/mm2, 3 s) stimuli, repeatedly applied after prolong pauses. Resting inhibition of pressure responses decreased the maximum discharge rate (MDR) evoked by the first stimulus in a train from the control value of 10.3 ± 1.5 Hz (n = 15, SEM) to 4.1± 1.0 Hz (n = 7) for lidocaine and to 6.3± 1.0 Hz (n = 15) for NPA. UD inhibition further decreased MDR evoked by the second and the third stimulus in a train: for lidocaine to 1.0 ± 0.7 Hz (n = 7) and 0.2 ± 0.1 Hz (n = 7); for NPA to 2.1 ± 0.8 Hz (n = 15) and 0.2 ± 0.1 Hz (n = 15). Resting inhibition of heat discharges decreased MDR evoked by the first stimulus from the control value of 6.0 ± 1.0 Hz (n = 28) to 2.4 ± 0.5 Hz (n = 8) for lidocaine and to 2.8 ± 0.3 Hz (n = 20) for NPA. UD inhibition further decreased MDR evoked by the second stimulus: in percentage to the first one, MDR was 57±14% (n = 8) for lidocaine and 56 ± 7% (n = 20) for NPA. Lidocaine and NPA transformed discharges evoked by a ramp heat stimulus, maintaining low frequencies (MDR < 2-3 Hz) and eliminating the higher ones. Tertiary amine lidocaine, but not quaternary NPA, elevated the thermal threshold by 2.8± 0.9 °C (n = 24, P < 0.01). UD inhibition of CMH unit termination indicates that it contains ionic channels with slow kinetics, thought to be tetrodotoxin-resistant sodium channels. Such UD inhibition allows us to explain the analgesic action of local anesthetics in low (subblocking) concentrations and propose local analgesia, which cuts the nociceptive signals off, but maintains the non-nociceptive ones.