The resistance of cutaneous feline polymodal C-fiber units to tetrodotoxin as revealed by mechanical and thermal stimulation

Abstract

Mechanical and thermal excitability of cutaneous feline polymodal C-fiber units is maintained under the action of subcutaneous tetrodotoxin injected in concentrations suppressing the mechanosensitivy of A~-units. A number of features of inhibition and excitation of C-fiber polymodal sensory units can be explained by existence of tetrodotoxinresistant Na channels in their termination. Key Words: nociception; slcin; CMH units; tetrodotoxin; Na channe&The cutaneous C-fiber mechano-and heat-sensitive (CMH) units are the primary elements of the nociceptive system in the warm-blooded animals [12]. The excitation of these sensors in humans evokes pain. The terminations of cutaneous CMH units are characterized not only by individual excitability, but also by the mode of inhibitory action of local anesthetics [2]. These features make it possible to distinguish in the structure of a CMH unit a particular subdivision, which differs from the proximal part of the axon by its reaction both to exciting and inhibiting procedures. This work studies the properties of sodium permeability of the CMH termination with the help of the thst sodium channel blocker tetrodotoxin (TTX). MATERIALS AND METHODSThe responses of 7 CMH and 17 mechanosensitive A~ milts were studied on 11 cats anesthetized with Clfloralose (40 mg/kg) and Urethane (600 mg/kg). The signals of individual fibers in a fine strand of saphenous nerve in the hindleg were recorded by a Deparhnent of Physiology, Cardiology Research Center, Moscow standard technique [4]. The cutaneous sensitive terminations of both sensory types were found in the medial part of the hindleg. Mechanical stinmli were applied to CMH units manually with calibrated Frey hair and to ~ units with a soft brush. The thresholds in mechanical sensitivity of CMH units were 25-50 g/mm 2. The thermal ramp stimuli were applied to CMH units by a radiant heat of a projector Imnp that was controlled by a feed-back signal fiom a thermocouple contacting the skin near the receptive site (Fig. 1). The parameters of thermal stinmlus were controlled by a computer. The thermal threshold was 39-41oC.For subcutaneous application of solutions the part of skin with a receptor was exfoliated: The control and test solutions were administered into this lumen (Fig. 1). The skin exfoliation and application of the control Ringer's solution did not modify the responses of CMH units. TI'X was added to Ringer's solution (in raM): NaC1 --154, KCI --5.6, CaCL --2.2, Tris-HCl --5.0; 37~ pH 7.3). To test the effect of TTX on the axons of the recorded CMH and A~ units, the test solutions were applied directly to the nerve tnmk with opened perineurium sheath. The neurograms were transformed into the d:ischarge 0007-4888/97/0010-0945518.00 9 Plemlm Publishin.q Corl~oralion