Nociceptor

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Nociceptor
Four types of sensory neurons and their receptor cells. Nociceptors shown as free nerve endings type A
Identifiers
MeSHD009619
Anatomical terminology

A nociceptor (from

Latin nocere 'to harm or hurt'; lit. 'pain receptor') is a sensory neuron that responds to damaging or potentially damaging stimuli by sending "possible threat" signals[1][2][3] to the spinal cord and the brain. The brain creates the sensation of pain to direct attention to the body part, so the threat can be mitigated; this process is called nociception
.

Terminology

action potentials, integration of pre- and postsynaptic signals, and influences from higher or central processes.[4] Due to historical misunderstanding, nociceptors are inappropriately referred to as pain receptors. Psychological factors can affect its perceived intensity, but all pain is real.[5]

Scientific investigation

Nociceptors were discovered by Charles Scott Sherrington in 1906. In earlier centuries, scientists believed that animals were like mechanical devices that transformed the energy of sensory stimuli into motor responses. Sherrington used many different experiments to demonstrate that different types of stimulation to an afferent nerve fiber's receptive field led to different responses. Some intense stimuli trigger reflex withdrawal, certain autonomic responses, and pain. The specific receptors for these intense stimuli were called nociceptors.[6]

Studies of nociceptors have been conducted on conscious humans as well as surrogate animal models. The process is difficult due to invasive methods that could change the cellular activity of nociceptors being studied, the inability to record from small neuronal structures, and uncertainties in

animal model systems as to whether a response should be attributed to pain or some other factor.[4]

Location

In mammals, nociceptors are found in any area of the body that can sense noxious stimuli. External nociceptors are found in

dorsal root ganglia or the trigeminal ganglia.[7]
The trigeminal ganglia are specialized nerves for the face, whereas the dorsal root ganglia are associated with the rest of the body. The axons extend into the peripheral nervous system and terminate in branches to form receptive fields.

Types and functions

Nociceptors are usually electrically silent when not stimulated.

noxious stimuli are detected and transduced into electrical energy.[8] When the electrical energy reaches a threshold value, an action potential is induced and driven towards the central nervous system
(CNS). This leads to the train of events that allows for the conscious awareness of pain. The sensory specificity of nociceptors is established by the high threshold only to particular features of stimuli. Only when the high threshold has been reached by either chemical, thermal, or mechanical environments are the nociceptors triggered.

In terms of their

myelination of their axon.[9][4] As a result, pain comes in two phases: an initial extremely sharp pain associated with the Aδ fibers and a second, more prolonged and slightly less intense feeling of pain from the C fibers. Massive or prolonged input to a C fiber results in a progressive build up in the dorsal horn of the spinal cord; this phenomenon called wind-up is similar to tetanus in muscles. Wind-up increases the probability of greater sensitivity to pain.[10]

Thermal

Thermal nociceptors are activated by noxious heat or cold at various temperatures. There are specific nociceptor transducers that are responsible for how and if the specific nerve ending responds to the thermal stimulus. The first to be discovered was

pain threshold are unknown at this time. The cool stimuli are sensed by TRPM8
channels. Its C-terminal domain differs from the heat sensitive TRPs. Although this channel corresponds to cool stimuli, it is still unknown whether it also contributes in the detection of intense cold. An interesting finding related to cold stimuli is that tactile sensibility and motor function deteriorate while pain perception persists.

Mechanical

Mechanical nociceptors respond to excess pressure or mechanical deformation. They also respond to incisions that break the skin surface. The reaction to the stimulus is processed as pain by the cortex, just like chemical and thermal responses. These mechanical nociceptors frequently have polymodal characteristics. So it is possible that some of the transducers for thermal stimuli are the same for mechanical stimuli. The same is true for chemical stimuli, since TRPA1 appears to detect both mechanical and chemical changes. Some mechanical stimuli can cause release of intermediate chemicals, such as

P2 purinergic receptors, or nerve growth factor, which can be detected by Tropomyosin receptor kinase A (TrkA).[11]

Chemical

Chemical nociceptors have TRP channels that respond to a wide variety of spices. The one that sees the most response and is very widely tested is capsaicin. Other chemical stimulants are environmental irritants like acrolein, a World War I chemical weapon and a component of cigarette smoke. Apart from these external stimulants, chemical nociceptors have the capacity to detect endogenous ligands, and certain fatty acid amines that arise from changes in internal tissues. Like in thermal nociceptors, TRPV1 can detect chemicals like capsaicin and spider toxins and acids.[12][11] Acid-sensing ion channels (ASIC) also detect acidity.[11]

Sleeping/silent

Although each nociceptor can have a variety of possible threshold levels, some do not respond at all to chemical, thermal or mechanical stimuli unless injury actually has occurred. These are typically referred to as silent or sleeping nociceptors since their response comes only on the onset of inflammation to the surrounding tissue.[7] They were identified using electrical stimulation of their receptive field.[4]

Polymodal

Nociceptors that respond to more than one type of stimuli are called polymodal.

neurotransmitters.[4]

Pathway

Ascending

anterolateral system. The former is reserved more for regular non-painful sensation, while the latter is reserved for pain sensation. Upon reaching the thalamus, the information is processed in the ventral posterior nucleus and sent to the cerebral cortex
in the brain via fibers in the posterior limb of the internal capsule.

Descending

As there is an ascending pathway to the brain that initiates the conscious realization of pain, there also is a descending pathway which modulates pain sensation. The brain can request the release of specific

diacetylmorphine
exhibit an analgesic effect.

Sensitivity

Nociceptor sensitivity is modulated by a large variety of mediators in the extracellular space, such as toxic and inflammatory molecules.[16][4] Peripheral sensitization represents a form of functional plasticity of the nociceptor. The nociceptor can change from being simply a noxious stimulus detector to a detector of non-noxious stimuli. The result is that low intensity stimuli from regular activity, initiates a painful sensation. This is commonly known as hyperalgesia. Inflammation is one common cause that results in the sensitization of nociceptors. Normally hyperalgesia ceases when inflammation goes down, however, sometimes genetic defects and/or repeated injury can result in allodynia: a completely non-noxious stimulus like light touch causes extreme pain. Allodynia can also be caused when a nociceptor is damaged in the peripheral nerves. This can result in deafferentation, which means the development of different central processes from the surviving afferent nerve. With this situation, surviving dorsal root axons of the nociceptors can make contact with the spinal cord, thus changing the normal input.[10]

Neural development

Nociceptors develop from

mechanoreceptors. All neurons derived from the neural crest, including embryonic nociceptors, express the tropomyosin receptor kinase A (TrkA), which is a receptor to nerve growth factor (NGF). However, transcription factors that determine the type of nociceptor remain unclear.[12]

Following sensory neurogenesis, differentiation occurs, and two types of nociceptors are formed. They are classified as either peptidergic or nonpeptidergic nociceptors, each of which express a distinct repertoire of ion channels and receptors. Their specializations allow the receptors to innervate different central and peripheral targets. This differentiation occurs in both perinatal and postnatal periods. The nonpeptidergic nociceptors switch off the TrkA and begin expressing RET proto-oncogene, which is a transmembrane signaling component that allows the expression of glial cell line-derived neurotrophic factor (GDNF). This transition is assisted by runt-related transcription factor 1 (RUNX1) which is vital in the development of nonpeptidergic nociceptors. On the contrary, the peptidergic nociceptors continue to use TrkA, and they express a completely different type of growth factor. There currently is a lot of research about the differences between nociceptors.[12]

In other animals

Nociception has been documented in non-mammalian animals,

sea slugs,[21] and larval fruit flies.[22] Although these neurons may have pathways and relationships to the central nervous system that are different from those of mammalian nociceptors, nociceptive neurons in non-mammals often fire in response to similar stimuli as mammals, such as high temperature (40 degrees C or more), low pH, capsaicin
, and tissue damage.

For example, in fruit flies, specific multidendritic sensory neurons play a role in nociception.[23] In mollusks, nociceptive responses are mediated by pedal sensory neurons.[24][25] Crustaceans, on the other hand, utilize a variety of sensory cell types, including chordotonal organs and mechanoreceptors, to detect potentially damaging stimuli (see also Pain in crustaceans).

See also

References

  1. ^ "NOI - Neuro Orthopaedic Institute". www.noigroup.com. Archived from the original on 2018-10-17. Retrieved 2017-10-13.
  2. ^ "Nociception and pain: What is the difference and why does it matter? - Massage St. Louis, St. Louis, MO". www.massage-stlouis.com. Archived from the original on 2018-11-01. Retrieved 2017-10-13.
  3. ^ Animals NR (8 December 2017). Mechanisms of Pain. National Academies Press (US) – via www.ncbi.nlm.nih.gov.
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  5. ^ "Pain is Weird: A Volatile, Misleading Sensation". Archived from the original on 2018-10-27. Retrieved 2018-10-27.
  6. ^ Sherrington C. The Integrative Action of the Nervous System. Oxford: Oxford University Press; 1906.
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  8. ^ Fein, A Nociceptors: the cells that sense pain http://cell.uchc.edu/pdf/fein/nociceptors_fein_2012.pdf
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