Thermal block of mammalian unmyelinated C fibers by local cooling to 15-25°C after a brief heating at 45°C

Abstract

The purpose of this study was to examine the changes in cold block of unmyelinated C fibers in the tibial nerve by preconditioning with heating and to develop a safe method for thermal block of C-fiber conduction. In seven cats under α-chloralose anesthesia, C-fiber-evoked potentials elicited by electrical stimulation were recorded on the tibial nerve during block of axonal conduction induced by exposing a small segment (9 mm) of the nerve to cooling (from 35°C to ≤5°C) or heating (45°C). Before heating, partial, reproducible, and reversible cold block was first detected at a threshold cold block temperature of 15°C and complete cold block occurred at a temperature of ≤5°C. After the nerve was heated at 45°C for 5-35 min, the threshold cold block temperature significantly (P < 0.05) increased from 15°C to 25°C and the complete cold block temperature significantly (P < 0.05) increased from ≤5°C to 15°C on average. The increased cold block temperatures persisted for the duration of the experiments (30-100 min) while the amplitude of the C-fiber-evoked potential measured at 35°C recovered significantly (P < 0.05) to ~80% of control. This study discovered a novel thermal method to block mammalian C fibers at an elevated temperature (15-25°C), providing the opportunity to develop a thermal nerve block technology to suppress chronic pain of peripheral origin. The interaction between heating and cooling effects on C-fiber conduction indicates a possible interaction between different temperature-sensitive channels known to be present in the mammalian C fibers.NEW & NOTEWORTHY Our study discovered that the temperature range for producing a partial to complete cold block of mammalian C-fiber axons can be increased from 5-15°C to 15-25°C on average after a preheating at 45°C. This discovery raises many basic scientific questions about the influence of temperature on nerve conduction and block. It also raises the possibility of developing a novel implantable nerve block device to treat many chronic diseases including chronic pain.

Keywords: block; cat; cold; heat; nerve.

Fig. 1.

Schematic drawing of the experimental setup. The tibial nerve was cut distal to the stimulation site and central to the recording site. The nerve was passed through a coil of copper tubing for thermal block. The temperature inside the coil was changed by running water of different temperatures through the tubing. A thermocouple was placed in the center of the copper coil to record temperature. Electrical stimulation was applied to the nerve by a tripolar cuff electrode distal to the coil and the evoked potential was recorded by a bipolar cuff electrode central to the coil. The nerve, coil, and electrodes were all immersed in warm mineral oil.

Fig. 2.

Effect of temperature on C-fiber axonal conduction. A: evoked potentials induced by stimulation of C fibers in the tibial nerve when a small segment of the nerve between the stimulation and recording electrodes is cooled to different temperatures (5–35°C). The mean conduction velocity is 0.7 m/s measured by the latency at the peak of the evoked potential at 35°C. Stimulus pulse: 28 V, 1 ms. B–D: the amplitude, latency, and duration of the evoked potentials change with temperature. The responses were normalized to that measured at 35°C; n = 7 cats. Mean conduction velocity is 0.75 ± 0.02 m/s. Stimulus pulses: 10–44 V, 1 ms. *Significantly (P < 0.05) different from 35°C (repeated measure one-way ANOVA).

Fig. 3.

Effect of 45°C heating on C-fiber axonal conduction. A: evoked potentials before, during, and after 5 min heating at 45°C in a cat. The mean conduction velocity is 0.76 m/s at 35°C. Stimulus pulse: 44 V, 1 ms. B: the average amplitude of evoked potentials decreases during the first 5 min of heating; n = 7 cats. *Significantly (P < 0.05) different from the amplitude before heating at 0 min (repeated measure one-way ANOVA).

Fig. 4.

The temperature for cold block of C-fiber conduction is increased after a brief heating at 45°C. A: evoked potentials in a cat showing that a temperature below 5°C is required to block C-fiber conduction, but the temperature is increased to 10–15°C by 45°C heating of the nerve for 5 min. The block effect at 10–15°C lasts for at least 45 min while the nerve conduction at 35°C largely recovers. The mean conduction velocity is 0.76 m/s at 35°C. Stimulus pulse: 44 V, 1 ms. B: in summary (n = 7 cats), after 5–35 min heating at 45°C the temperature for complete block of C-fiber conduction increased from 5°C to 15°C. This block effect is maintained for at least 30–100 min while on average 80% of nerve conduction recovers at 35°C. *Significantly (P < 0.05, repeated measure one-way ANOVA) different from control. #Significantly (P < 0.05, repeated measure two-way ANOVA) different from the amplitude after 45°C heating.

Fig. 5.

Recovery of C-fiber axonal conduction after 45°C heating. A: evoked potentials recorded at 35°C or 10°C in a cat before and after 20 min heating at 45°C. The mean conduction velocity is 0.76 m/s at 35°C. Stimulus pulse: 12 V, 1 ms. B: the evoked potentials are monitored for 30–100 min after 5–35 min heating at 45°C in different cats (n = 7). After heating, the amplitude of C-fiber-evoked potential largely recovers at 35°C but is blocked at 10–20°C.