Nozizeption

Nociception is the perception and reception of stimuli that potentially or actually harm the body (lat. nocere= harm). These stimuli are registered by nociceptors and transmitted to the brain via afferent pain fibers. The associated sensation is pain.

Excitation of nociceptors by noxious stimuli results from activation of ion channels and receptors of sensory nerve endings. Mechanical stimuli are thought to open a cation channel at the non-corpuscular, unmyelinated sensory fiber terminals, thereby depolarizing them. The exact opening mechanism is unknown.

Depending on their sensitivity to certain stimuli, a distinction is made between:

• Mechanosensitive nociceptors: React to mechanical stimuli
• Thermosensitive nociceptors: react to thermal stimuli (heat >45°C or cold <5°C) Cold and warm sensors occur in the skin in different densities. The highest density of cold spots is in the face. The lowest density is found on the acras. Cold spots are completely absent on the gaans penis.
• Polymodal nociceptors: Respond to thermal (heat >42°C or cold <15°C), mechanical, and chemical stimuli.

The transmitters of the nociceptors (Aδ and C fibers) are: substance P, CGRP (calcitonin gene-related peptide) and/or glutamate. These transmitter substances are released from the nociceptive nerve terminals and provide synaptic transmission of pain information in the posterior horn of the spinal cord. H+, K+, bradykinin, histamine, serotonin and prostaglandins act as pain mediators. Among the prostaglandins, PGE2 is a particularly important pain mediator. It promotes pain perception by sensitizing nociceptors, thereby increasing their excitability. Furthermore, PGE2 facilitates spinal transmission (Graefe KH et al. 2016).

Mechanisms of nociception: Pain results from mechanical, thermal or chemical (pain mediators) stimulation of specific pain receptors (nociceptors). Nociceptors are present in almost every tissue. The highest density is found in the skin. No nociceptors are present in the brain or in parenchymal organs. Under physiological conditions, nociceptors respond only to noxious mechanical, thermal, and chemical stimuli acting on their receptive area. Nociceptors consist of thin, non-corpuscular, unmyelinated sensory fiber endings with no special structural features. They are covered in sections by Schwann cells. The cell bodies themselves are located in the spinal ganglion. The conversion of noxious stimuli into electrical potentials takes place in the terminals. Most nociceptors have unmyelinated axons (C-fibers). A portion of nociceptors have thinly myelinated axons (Aδ-fibers).

Ascending nociceptive neuron system: The excitation of the primary afferent Aδ and C fibers, are carried away via the posterior spinal root to the posterior horn of the spinal cord. From there, the excitation potential is carried away via appropriate neural pathways to higher sections of the central nervous system, where it is propagated. All neurons involved in this process together form the ascending nociceptive neuron system.

Descending antinociceptive neuron system: The descending antinociceptive neuron system exerts a control function of the ascending nociceptive and thus has an antagonistic effect on the ascending antinociceptive neuron system (endogenous pain inhibition). An important inhibitory/pathway function on the spinal cord neurons is mainly exerted by the catecholaminergic core areas in the brainstem. An inhibitory effect is exerted mainly via noradrenaline (α2-receptors) and serotonin (5-HT) via 5-HT1A-, 5-HT2-, 5-HT7-receptors, whereas serotonin can also have pathway effects via 5-HT3-receptors. Transmitter functions are exerted by endogenous neuropeptides (opioid peptides also endogenous opioids, these include: encaphalins, endorphins, dynorphins). A release of the endogenous opioids and activation of the opioid receptors inhibits the neuronal nociceptive activity.