The TRP protein family was initially discovered in Drosophila and was found to play a role in the phototransduction process in Drosophila photoreceptors. Hence, the name TRP refers to the fact that a mutation in the gene leads to a transient depolarizing response to a light stimulus instead of the normal sustained response. Based on sequence homology, numerous genes encoding TRP proteins have been identified in mammals (27 in humans alone), which are currently categorized into seven subfamilies. TRP channels are permeable to cations and have a structure similar to voltage-gated K+ channels. They exist as homotetramers or heterotetramers, with each subunit having six transmembrane domains. TRP proteins have various functions, including phototransduction, chemotransduction, and mechanotransduction, and they are expressed in different cell types. The TRP proteins listed in Table 7.1 appear to act as temperature sensors with distinct thermal sensitivities that cover the range of physiologically relevant temperatures.

The modulation of the transduction process, similar to low-threshold mechanoreceptors for innocuous touch sensations, involves the activation of various nociceptor transduction proteins. This activation leads to a generator potential that causes spiking of the afferent, transmitting information to the central nervous system (CNS). Additionally, the activation of nociceptors results in the local release of different chemical compounds, such as substance P (SP) and calcitonin gene-related protein (CGRP), which leads to neurogenic inflammation characterized by edema and redness of the surrounding skin. Furthermore, these substances may activate silent nociceptors, allowing them to respond to subsequent damaging stimuli. Sensitization of silent nociceptors is believed to be responsible for allodynia (painful sensations caused by previously innocuous stimuli) and hyperalgesia (increased pain response to already painful stimuli). Thermal hyperalgesia, specifically, is caused by sensitization of TRPV1 channels, while changes in Piezo2 current are associated with mechanical hyperalgesia and allodynia.

The somatosensory system also involves centrifugal control, where sensory experience is not solely the passive detection of environmental events but also relies on exploration of the environment. Tactile cues are obtained by moving the hand over a surface, while visual cues result from scanning targets with the eyes. Therefore, sensory information often arises from motor system activity. Furthermore, transmission in pathways to the sensory centers of the brain is regulated by descending control systems, allowing the brain to filter incoming sensory messages. This enables the brain to focus on important information while disregarding unimportant stimuli. The tactile and proprioceptive somatosensory pathways are regulated by descending pathways originating in the cerebral cortex's S-I and motor regions. For instance, cortical projections to the dorsal column nuclei play a role in controlling the sensory input transmitted through the dorsal column–medial lemniscus pathway.
MembersoftheTRPproteinfamilywerefirstidentifiedinDrosophila andwerefoundtobepartofthephototransductionprocessinDrosophila photoreceptors.Thusthename(TRP) referstothefactthatamutationinthegeneleadstoatransientdepolarizingresponsetoalightstimulusinsteadofthenormalsustainedresponse.Onthebasisofsequencehomology,anumberofgenesencodingTRPproteinshavebeenfoundinmammals(27inhumansalone),whicharecurrentlydividedintosevensubfamilies.TRPchannelsarecationpermeableandhaveastructuresimilartovoltage-gatedK+ channels.Theyarehomotetramersorheterotetramers.Eachsubunithassixtransmembranedomains.TRPproteinsappeartohaveavarietyoffunctions(e.g.,phototransduction,chemotransduction,andmechanotransduction)andareexpressedinanumberofcelltypes.Thoselistedin
Table7.1 appeartoactastemperaturesensorswithdistinctthermalsensitivitiesthatspantherangeofphysiologicallyrelevanttemperatures.
Modulation of the Transduction Process
As with the low-threshold mechanoreceptors for innocuous touch sensations, activation of the various nociceptor
Thefourthletterinthenameidentifiesthesubfamilyandwaschosenbecauseofthefirstmemberofthesubfamilyidentified:V,vanilloid;M,melastatin;A,ankyrin-like.Eachoftheproteinslistedisexpressedinatleastsomedorsalrootganglioncells,buttheyarealsoexpressedinothercelltypes.
CHAPTER 7 The Somatosensory System transduction proteins leads to a generator potential that causes spiking of the afferent, which transmits information to the CNS. In addition, activation of nociceptors also leads to local release of various chemical compounds, including tachykinins (substance P [SP]) and calcitonin gene–related protein (CGRP). These substances and others released from the damaged cells cause neurogenic inflammation (edema and redness of the surrounding skin).
In addition to causing a local reaction, these substances may serve to activate the insensitive or silent nociceptors mentioned earlier, such that they can henceforth respond to any subsequent damaging stimuli. Sensitization of silent nociceptors has been suggested to underlie allodynia (elicitation of painful sensations by stimuli that were innocuous before an injury) and hyperalgesia (increase in the level of pain felt to already painful stimuli). Thermal hyperalgesia is due to sensitization of TRPV1 channels. The Piezo2 current is increased by substances known to cause mechanical hyperalgesia and allodynia, suggesting changes in this current underlie these phenomena.
Centrifugal Control of Somatosensation
Sensory experience is not just the passive detection of environmental events. Instead, it more often depends on exploration of the environment. Tactile cues are sought by moving the hand over a surface. Visual cues result from scanning targets with the eyes. Thus sensory information is often received as a result of activity in the motor system. Furthermore, transmission in pathways to the sensory centers of the brain is regulated by descending control systems. These systems allow the brain to control its input by filtering the incoming sensory messages. Important information can be attended to and unimportant information can be ignored.
The tactile and proprioceptive somatosensory pathways are regulated by descending pathways that originate in the S-I and motor regions of the cerebral cortex. For example, cortical projections to the dorsal column nuclei help control the sensory input that is transmitted by the dorsal column– medial lemniscus pathway.