6.1 Human Skin on the Molecular Scale

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the three-dimensional channel structure seems to be at least part of the cause [2]. Most

of these channels are also voltage dependent, and the voltage does change the tempera-

ture range somewhat. There are additionally some chemicals that allosterically regulate

temperature range and/or voltage dependency. Even though each channel has its own

temperature range, the actual sensation of heat can usually only be explained by the

combination of several channels.

The ion channels that react to noxious (painful) temperatures seem to also be the

ones that react to noxious chemicals, such as capsaicin from hot chili peppers [3] or

acid in concentrations that cause burns [2] (Table 6.1). At the same time, each of these

channels are located not only in skin, but also, e. g., in the tongue, some organs, and the

central nervous system. Inside of organs, the channels seem to be connected with the

inflammation response.

As soon as the channel is activated, the signal is either transferred directly to an-

other neuron, and thus to the brain via a synapse, or transferred indirectly via a chemi-

cal release of the skin cell to activate another neuron that then has a synaptic connection

to other neurons and the brain [2]. Skin cells can produce cytokines, neural growth fac-

tors, and neurotransmitters that all could function as an indirect signal. One path for the

signals to the brain includes the limbic system, which generates an emotional response

to pain [4].

Some of the channels seem also be part of the temperature regulation of the body

as a result of sensing the temperature [2, 5]. At least locally, some of the channels initiate

blood vessel dilation or restriction, which regulates temperature in that area of skin.

The temperature control cycle is then connected to other homeostasis cycles, such as fat

cycles in the brown adipose tissue that is used to internally create heat [6]. The details of

most of these processes are not yet understood. Questions that remain are the specific

gating mechanism of these channels, how they are regulated by noxious chemicals, how

their function differs in different organs, and how the transfer of signals occurs. As soon

as signal transfer has occurred, however, the actions are, as always, controlled by the

spinal cord or the brain.

The signal for mechanical pressure and its pain is sensed in an analogous fashion.

There are a variety of nerve fibers that sense pressure; in fact, some of the nerve fibers

sensing temperature also sense pressure (Figure 6.3) [7–9]. There are different sensory

corpuscles present in human hairy skin [9]. Low threshold mechanoreceptors contact

with epithelial Merkel cells or Schwann-like cells forming Merkel cell neurite complexes

(slowly adapting), Meissner corpuscles (rapidly adapting), Pacinian corpuscles (rapidly

adapting), and Ruffini endings (slowly adapting). Hairs contain several nerve endings;

occasionally, hairs have associated Merkel cells, Ruffini and even Pacinian corpuscles.

These sensory nerve cells are concentrated in “touch domes”, slight dermal protrusions

or bumps [10]. Touch domes also include Merkel cells. Merkel cells are specialized cells in

the epidermis that sense light touch via an indirect pathway, i. e., the Merkel cells release

a chemical that only then will activate a nerve cell (Figure 6.1). Merkel cells react to light

touch slowly, since the signal needs to diffuse first to neurons before it can be detected.