What is the function of nociceptors


from Latin: nocere - damage
Synonyms: pain reception, pain perception
English: nociception

1 definition

Under Nociception one understands the perception of pain. The receptors responsible for this process are called Nociceptors. As free nerve endings of the sensitive neurons of the spinal cord, nociceptors occur in all pain-sensitive tissues in the body.

2 Definition of terms

Nociception and pain are 2 different entities:

  • Nociception refers to the receipt of signals in the CNS that are mediated by specialized sensory receptors (nociceptors) and provide information about tissue damage.
  • Pain is an uncomfortable, intense sensory and emotional experience that is associated with actual or possible tissue damage.

Nociception is possible without pain, but organic pain is never possible without nociception.

3 types of pain

Depending on their location, nociceptors trigger different types of pain:

3.1 Somatic pain

3.1.1 Surface pain

Surface pain is the pain that is perceived by nociceptors located superficially in the skin. The localization of the pain can be clearly assigned to the damaged area.

3.1.2 Deep pain

Depending on the location of the nociceptors, deep pain is divided into:

The deep pain is much more difficult to localize. This is due to the different fiber characteristics and the different projection areas of the pain fibers (see below).

3.2 Visceral pain

In visceral pain, the localization of the nociceptors is within the internal organs. Classic examples are kidney or biliary colic, which is caused by stretching stimuli in the smooth muscles.

4 histology

Histologically, nociceptors can be classified into C fibers and Aδ fibers based on different fiber properties.

4.1 C fibers / Class IV fibers

C fibers, which are also known as class IV fibers, are unmyelinated and their covering by Schwann cells is interrupted in places. Their line speed is therefore only very low at 1 m / s.

4.2 Aδ fibers / Class III fibers

Aδ fibers are thinly myelinated. Their line speed is up to 30 m / s faster than that of the C fibers.

4.3 Pain perception as a function of fiber properties

In the perception of pain as a response to superficial tissue damage, two different pain sensations can be distinguished due to the different fiber qualities. These are due to the different conduction properties of the nociceptors. The first response is the early "light" pain, the rapidly conducting Aδ fibers. After that, the late "dull" pain mediated by the C-fibers occurs.

C-fibers also cause deep pain, which is perceived as dull.

Superficial C-fibers in the transition area between epidermis and dermis mediate the pruritoceptive pruritus that occurs in dermatoses (e.g. psoriasis) as one of the main symptoms.

5 physiology

Each nociceptor can be assigned a specific area (receptive field) within which pain-inducing stimuli lead to the development of an action potential.

5.1 Stimulus modalities

Nociceptors are sensitive to different stimulus modalities. A distinction is made according to their response behavior:

  • Polymodal nociceptors: They react to mechanical (e.g. pressure), thermal and chemical stimuli. Depending on the fiber properties, they can be further differentiated into:
    • A-polymodal nociceptors and
    • C-polymodal nociceptors
  • Mechanonociceptors: They only react to mechanical stimuli.
  • Silent nociceptors: Silent nociceptors are not excitable in healthy tissue. In the context of inflammation, however, they become sensitive to pain stimuli by lowering the stimulus threshold.

5.2 Transduction

The neuronal transduction of the nociceptors takes place on the basis of various ion channels in the nociceptor membrane. Each channel is specific to certain stimuli. Exposure to a pain-inducing stimulus causes the respective channel to open. Cations flow in (Na+, Approx2+) and thus to an intracellular change in the ionic environment. Depending on the voltage, sodium channels open and depolarization occurs.

5.3 channels

  • Mechanical-chemical transduction: The channels of mechanical transduction are not yet clearly identified.
  • Thermal-chemical transduction Thermal transduction takes place using polymodal TRPV channels (transient receptor potential vanilloid receptors). Different receptor subtypes are distinguished on the basis of different stimulus modalities.
    • TRPV1 channels: open at temperatures> 42 ° C and are also sensitive to capsaicin. Capsaicin is contained in pepper, hot paprika and chilli and is responsible for the sensation of spiciness. The sensation of sharpness is therefore not due to the sense of taste, but to pain receptors.
    • TRPV2 channels: open at temperatures> 52 ° C and are not sensitive to capsaicin.
    • TRPA1 channels: are activated by various molecules (e.g. allyl isothiocyanate, hydrogen peroxide or 4-hydroxynonenal) and, if necessary, by cold.
  • Chemical irritation: A decrease in the pH value leads to the opening of acid-sensitive channels (ASIC = acid sensing ion channels). This happens when exposed to acid, but also when acidic metabolites accumulate in the tissue as a result of ischemia (e.g. myocardial infarction).
  • Inflammation-related sensitization: In addition, the nociceptor membrane has a large number of receptors for inflammation mediators (bradykinin, histamine, prostaglandins, cytokines, H+-Ions, K+Ions), which sensitize the nociceptor by lowering the stimulus threshold. In the normal state, nociceptors are high-threshold receptors; a high-threshold stimulus is required to trigger an action potential. In the case of inflammation, the sensitization causes primary hyperalgesia. In addition, there is an additional recruitment of silent nociceptors, which acquire thermo- and mechanosensitive abilities through sensitization. The cellular mechanism of sensitization is based on enzymatic phosphorylation of the ion channels by protein kinases.

In pain therapy, the sensitization of the nociceptors can be dampened with nonsteroidal anti-inflammatory drugs (NSAIDs). As non-specific inhibitors of cyclooxygenase (COX-1 and COX-2), NSAIDs inhibit prostaglandin synthesis.

5.4 Pain management

5.4.1 Peripheral pain conduction

The action potential is passed on via the dendrites of the sensitive neuron (1st neuron; pseudounipolar neuron). At the fork of the dendrite and axon (crus commune) it is passed on directly to the axon, bypassing the perikaryon, which enters the posterior horn of the spinal cord (cornu posterius medullae spinalis). Here, in layers I-III (laminae spinales I-III) of the gray matter (substantia grisea), the switchover to the second neuron takes place.

5.4.2 Interconnection at the spinal cord level

  • Aδ fibers are switched to neurons with ascending fibers, especially in layer I (lamina spinalis I) of the gray matter.
  • C fibers have a longer path. In layers II and III, they are initially connected to neurons in layer V at the segmental spinal cord level via interneurons.

5.4.3 Central pain management and processing

Together, the pain afferents of the spinal cord in the anterior cord (anterolateral tract / lemniscus spinalis) pull to supraspinal centers, in which reflex physical reactions are triggered (formatio reticularis), the pain is assessed affectively (limbic system) and localization (somatosensory cortex) is made possible. Conversely, higher brain centers are also capable of influencing pain perception (pain modulation) through descending antinociceptive pathways.