Nociceptors are pain sensors that report actual or impending tissue injury as a pain stimulus to the brain for further processing. Three groups of nociceptors are able to differentiate between mechanical, thermal, and chemical overloads. Nociceptors are distributed throughout tissues except in the mesenchyme of the brain, lungs, and liver; a particular cluster is found in the skin.
What are nociceptors?
Nociceptors are sensory nerve endings that belong to the class of mechanoreceptors and are found throughout the tissues of the body, except in the mesenchyme of the liver, lungs, and brain, the specialized functional tissue of organs. A particular cluster of nociceptors is found in the skin. Unlike the other mechanoreceptors, the nerve endings of the nociceptors do not have special sensory heads, but are so-called free nerve endings that branch out toward the periphery. Three different groups of nociceptors allow differentiation of pain sensation between mechanically, thermally or chemically triggered actual or impending injuries. Depending on the type and location of the nociceptors, pain stimuli can be localized well or less well. The dense distribution of nociceptors in the skin usually allows good localization, while nociceptors located far inside in the muscles, on the bones and in the connective tissue usually only trigger a dull pain sensation that cannot be localized exactly. This is known as deep pain, while pain that can be localized well in the skin is also known as surface pain. Above this, nociceptors in the viscera can trigger visceral pain, which is also poorly localizable and can sometimes be very severe, such as in renal colic or appendicitis.
Anatomy and structure
Depending on their function, nociceptors consist of afferent nerve fibers with different structures that differ in their stimulus generation and transmission behavior. A group of mechano-nociceptors that respond to strong mechanical stimuli such as pressure, impact, pricking and pulling, and twisting fall under the category of A-delta fibers with a diameter of 3 – 5 µm and are surrounded by a thin myelin layer. Their stimulus transmission speed is 15 m/sec. Weaker mechanical stimuli are detected by mechanoreceptors of the tactile system, with which the nociceptor system is closely connected via synapses. The group of thermo-nociceptors, which respond to temperature stimuli above 45 degrees Celsius and to cold stimuli, generally belong to the C-polymodal afferents, which also respond to strong mechanical stimuli and to chemical stimuli. The nerve fibers are extremely thin, 0.1 to 1 µm, have no medullary sheath, and are characterized by a slow transmission speed of about 1 m/sec, which is unsuitable for generating protective reflexes. C-fibers also predominate in visceral nociceptors, which are responsible for producing dull, pulling deep pain. Characteristic of nociceptors of all categories are their free branching nerve endings, which do not bear specialized sensory heads. Substances that excite nociceptors are called algogens. Well-known algogens include neurotransmitters such as serotonin, histamine, and bradykinin, a blood-vessel constricting polypeptide.
Function and roles
In many cases, nociception overlaps with the tactile and haptic sensory systems because both systems must have qualitatively similar sensory capabilities. However, nociception is concerned with avoiding situations that have led to injury in the future or with immediately interrupting – even reflexively if necessary – situations that would lead to injury if they were continued. The main task of the various nociceptors, therefore, is to report mechanical, thermal, or chemical stimuli that have led to injury to the CNS as a pain stimulus, rather than as a quantitave sensory stimulus like the haptic and tactile systems. The CNS then summarizes all available information and applies the appropriate pain stimulus. At the same time, the sensory parameters that led to the injury are stored in pain memory to avoid such situations in the future. This means that the nociceptors are sensitized accordingly. A perceived pain cannot be triggered directly by the nociceptors, but is an expression of a processing process of certain centers in the CNS.Not only does “pain” occur, but other vegetative reactions such as changes in blood pressure and heart rate, changes in intestinal peristalsis, motor reactions such as reflex movements, facial expressions and much more can be triggered simultaneously. Nociceptors serve to protect the body from injury. They perform a warning function when parameters are about to be exceeded, which can lead to injury.
Diseases
Problems related to pain perception can directly affect nociceptors via a lowering or raising of their response threshold or through general dysfunction. More common than a general dysfunction of the nociceptors are problems in the further processing of the nociceptive action potentials. This is then no longer classic nociceptive pain, but neuropathic pain, which is often chronic, i.e. persists even when the immediate cause of the pain trigger has already been eliminated. What causes chronic neuropathic pain is not (yet) fully understood. Neuropathic pain can be associated with positive or negative symptoms, i.e., in the case of positive symptoms, the stimulus threshold for triggering pain sensation is reduced in the form of hyperalgesia, i.e., pain sensation occurs with low stimuli. Opposite symptoms are also known, which can lead to reduced pain sensation up to complete insensitivity to pain, analgesia. In the well-known diabetic neuropathy, which is caused by damage to the pain-signaling nerves, positive and negative symptoms occur side by side. Fibromyalgia or soft tissue rheumatism is also associated with neuropathic pain sensation disorders. In most cases, this is a form of hyperalgesia. An example of negative symptoms to analgesia is offered by the mental illness of borderline personality disorder. Affected individuals may even inflict cuts on themselves without feeling pain.
