112

౪

6 Skin, The Body’s Largest Organ

Figure 6.3: Scheme of the different sensory corpuscles present in human hairy skin. 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 adapt-

ing), and Ruffini endings (slowly adapting). Hairs contain several nerve endings; occasionally, hairs have

associated Merkel cells, Ruffini and even Pacinian corpuscles. (adapted from [9]).

As with temperature, extreme pressure will be sensed as pain. When pain is sensed

it is highly regulated. There are additional receptors that can up- or down-regulate

the pain sensation; some of these receptors are also located at the nerve ending of the

sensory neuron [11]. One example is the endothelin-1 receptor (Figure 6.4). Up- or down-

regulation usually occurs via a signal transduction pathway and has several points

where a variety of different chemicals can modulate transduction, either directly or

allosterically. Some of these are redundant pathways. One such regulation is the in-

creasing pain you feel when pressure is applied for a long time, but also the reduction

of pain after an initial, short-term stimulus. Additionally, heat might modulate pain

perception as well, which might explain why some sensor elements are activated by

both.

One of the multifunctional sensor elements we have already seen: Transient re-

ceptor potential ion channel TRPV4, which is one of the channels for sensing heat (see

Figure 6.2, Table 6.1) [12]. It is one of the channels opening at higher temperature that

is also linked to pain and activation by chemicals (specifically capsaicin). It is widely

distributed. TRPV4 mutations in humans lead to impaired bone development, motor

dysfunction, sensory loss of the combined thermal/pain sensation, abnormal sensation

of osmolarity and blood salt concentration, hearing impairment, bladder dysfunction,

and airway dysfunction [12]. Mutations in animals suggest even more functions, includ-

ing the barrier function of skin, insulin secretion, and liver function—there might be

more. The connection of all of these dysfunctions to the heat and mechanical sensor are

still under debate. TRPV4 works with several signal transduction pathways; these path-

ways give some hints as to how this might be possible (Figure 6.5). Additionally, there

are different mechanical stimuli that the ion channel reacts to differently: membrane

stretching, membrane press or pull, shear stress, and swelling of the cell in hypotonic

solutions.