Efficiency of cutaneous heat diffusion after local hyperthermia for the treatment of itch

Abstract

Background: Today, itching is understood as an independent sensory perception, which is based on a complex etiology of a disturbed neuronal activity and leads to clinical symptoms. The primary afferents (pruriceptors) have functional overlaps with afferents of thermoregulation (thermoceptors). Thus, an antipruritic effect can be caused by antagonizing heat-sensitive receptors of the skin. The ion channel TRP-subfamily V member 1 (TRPV1) is of particular importance in this context. Repeated heat application can induce irreversible inactivation by unfolding of the protein, causing a persistent functional deficit and thus clinically and therapeutically reducing itch sensation.

Material and methods: To demonstrate relevant heat diffusion after local application of heat (45°C to 52°C for 3 and 5 seconds) by a technical medical device, the temperature profile for the relevant skin layer was recorded synchronously on ex vivo human skin using an infrared microscope.

Results: The results showed that the necessary activation temperature for TRPV1 of (≥43°C) in the upper relevant skin layers was safely reached after 3 and 5 seconds of application time. There were no indications of undesirable thermal effects.

Conclusion: The test results show that the objectified performance of the investigated medical device can be expected to provide the necessary temperature input for the activation of heat-sensitive receptors in the skin. Clinical studies are necessary to prove therapeutic efficacy in the indication pruritus.

Keywords: TRPV1; concentrated heat; itch; local hyperthermia; pruritus.

FIGURE 1

Experimental setup of the measuring track with representation of the individual components

FIGURE 2

Overlay of magnification‐identical image of skin sample cryocut (left) and false color‐coded IR image (right) for the identification of the anatomical skin layers in the IR image

FIGURE 3

Mean temperature gradients based on the anatomical layers after 3 s application duration. The beginning of the temperature entry and the activation range of the TRPV1 (>42–43°C) are shown

FIGURE 4

Mean temperature gradients based on the anatomical layers after 5 s application duration. The beginning of the temperature entry and the activation range of the TRPV1 (>42–43°C) are shown

FIGURE 5

Mean temperature gradients in the vital epidermis (target compartment) based on the application temperature after 3 s application duration

FIGURE 6

Mean temperature gradients in the vital epidermis (target compartment) based on the application temperature after 5 s application duration

FIGURE 7

Min/max temperature gradients in the vital epidermis based on the respective application temperature after 3 s application duration

FIGURE 8

Min/max temperature gradients in the vital epidermis based on the respective application temperature after 5 s application duration