The Nociceptors Are the receptors on the skin, joints and organs that capture pain. They are also called detectors of noxious stimuli, as they are able to distinguish between harmless and harmful stimuli.
These receptors are at the end of the axons of Neurons Sense, and send painful messages to the spinal cord And the brain.
The nociceptive word comes from the Latin"nocer"that means to hurt or to do damage. Thus, nociceptive means"sensitive to noxious stimuli". Noxious stimuli are those that damage tissue and activate nociceptors.
Thus, nociceptors are sensory receptors that pick up signals from deteriorated tissue or the threat of damage. In addition, they respond, indirectly, to the chemicals released by the injured tissue.
These receptors are free nerve endings that are found in the skin, muscles, joints, bones and viscera.
The analysis of pain is extremely complicated. Be aware of pain And emotionally react to it are processes that are controlled within Our brain . Most of the senses are mainly informative, while pain serves to protect us.
Pain has a survival function of living beings. It serves to realize potentially harmful stimuli and to move away from them as soon as possible. That is why people who do not feel pain can be in serious danger, as they can burn themselves, cut themselves or be beaten for not going away in time.
It has been found that these nerve endings have TRP (transient potential receptors) channels that detect damage. A wide variety of noxious stimuli are interpreted by these receptors. This is done by initiating action potentials in the nerve fibers of pain that reach the spinal cord.
The cell bodies of the nociceptors are located, above all, in the dorsal root and in the Trigeminal nodes . While there are no nociceptors in the central nervous system.
Anatomy of the nociceptors
It is difficult to study nociceptors and there is still much to know about Pain mechanisms .
However, it is known that skin nociceptors are a group of extremely heterogeneous neurons. They are organized in ganglia (groups of neurons) that are outside the central nervous system, in the periphery.
These sensory ganglia interpret the external harmful stimuli of the skin up to meters away from their cellular bodies (Dubin & Patapoutian, 2010).
However, the activity of the nociceptors does not in itself produce the perception of pain. For this, the information of nociceptors must reach the higher centers (central nervous system).
The speed of pain transmission depends on the diameter of the axons (extensions) of the neurons and whether they are myelinated or not. The Myelin Is a substance that covers the axons and facilitates the conduction of the nerve impulses of the neurons, causing them to go faster.
Most nociceptors have non-myelinated axons of small diameter, known as C-fibers. They are organized in small groups surrounded by Schwann cells (of support).
The rapid pain, therefore, is related to the nociceptors of the fibers A. Their axons are covered of myelin and take the information much faster than the previous ones.
Nociceptors of fibers A are sensitive mainly to extreme temperatures and mechanical pressures.
Types of nociceptors and functions
Not all nociceptors respond in the same way and with the same intensity to noxious stimuli.
They are divided into several categories, depending on their responses to mechanical, thermal or chemical stimulation released by injury, inflammation or tumors.
As a curiosity, a distinctive feature of nociceptors is that they can be sensitized by prolonged stimulation, beginning to respond to different sensations.
Nociceptors of the skin or cutaneous
This type of nociceptors can be differentiated into four categories according to their function:
- High-threshold mechanoreceptors : Also called specific nociceptors, consist of free nerve endings of the skin that are activated before strong pressures. For example, when you hit, stretch or press the skin.
- Other nociceptors appear to respond to intense heats , Acids and the presence of capsaicin. The latter is the active component of hot chili. These fibers contain VR1 receptors. They are responsible for catching the pain produced by high temperatures (burns on the skin or inflammation) and the spicy.
- Another class of nociceptive fiber has ATP-sensitive receptors. He ATP It is produced by the mitochondria that are a fundamental part of the cell. ATP is the main energy source of cellular metabolic processes. This substance is released when a muscle is injured or when the blood supply is obstructed in a certain part of the body (ischemia).
It is also released when there are fast growing tumors. For this reason, these nociceptors can contribute to the pain that arises in migraines, angina, muscle injuries or cancer.
- Polymodal nociceptors: These respond to intense stimuli such as thermal and mechanical, as well as chemical substances, such as the types mentioned above. They are the most common type of C (slow) fibers.
Cutaneous nociceptors are only activated with intense stimuli, and in the absence of them they are inactive. Depending on your driving speed and response, you can distinguish two types:
- Nociceptors A- δ: Are located in the dermis and epidermis, and respond to mechanical stimulation. Its fibers are covered with myelin, which implies rapid transmission.
- Nociceptors C: As previously mentioned, lack myelin and their driving speed is slower. They are found in the dermis and respond to stimuli of all kinds, as well as to chemicals secreted after a tissue injury.
Nociceptors of the joints
The joints and ligaments have high threshold mechanoreceptors, polymodal nociceptors, and silent nociceptors.
Some of the fibers containing these receptors have neuropeptides such as substance P or Peptide associated with the calcitonin gene . When these substances are released there appears to be a development of inflammatory arthritis.
In muscles and joints there are also nociceptors of type A-δ and C. The former are activated when there are sustained muscular contractions. While the C respond to heat, pressure and ischemia.
Visceral nociceptors
The organs in our body have receptors that detect temperature, mechanical pressure and chemicals contain silent nociceptors. Visceral nociceptors are scattered from each other several millimeters apart. Although, in some organs, there may be several centimeters between each nociceptor.
All the harmful data captured by the viscera and the skin are transmitted to the central nervous system through different routes.
The vast majority of visceral nociceptors have unmyelinated fibers. Two classes can be distinguished: the high threshold fibers that are only activated with intense noxious stimuli, and the non-specific ones. The latter can be activated against both harmless and harmful stimuli.
Silent nociceptors
It is a type of nociceptors that are in the skin and in the deep tissues. These nociceptors are called so because they are silenced or at rest, that is, they normally do not respond to harmful mechanical stimuli.
However, they may"wake up"or begin responding to mechanical stimulation after injury or during inflammation. This may be due to the continued stimulation of the injured tissue decreasing the threshold of this type of nociceptors, causing them to begin to respond.
When silent nociceptors are activated it can be induced Hyperalgesia (Exaggerated pain precept), central sensitization and allodynia (it consists of feeling pain from a stimulus that normally does not produce it). Much of the visceral nociceptors are silent.
In short, these nerve endings are the first step that would initiate our perception of pain. They are activated through contact with a noxious stimulus, such as touching a hot object or cutting a skin.
These receptors send information regarding the intensity and location of the painful stimulus to the central nervous system.
Stimuli that activate the nociceptors
These receptors are activated when a stimulus causes tissue damage or is potentially harmful. For example, when we strike or perceive extreme heat.
Tissue damage results in the release of a wide variety of substances in the injured cells, in addition to new components that are synthesized at the site of the damage. These substances can be:
Proteins kinases and globulin
It appears that the release of these substances into damaged tissues produces severe pain. For example, it has been observed that injections below the skin of globulin cause intense pain.
Arachidonic acid
This is one of the chemicals that are secreted during tissue damage. Subsequently it is metabolized in prostaglandin and cytokines. Prostaglandins increase the perception of pain and make nociceptors more sensitive to it.
In fact, aspirin eliminates pain by blocking arachidonic acid from becoming prostaglandin.
Histamine
After tissue damage histamine is released into the surrounding area. This substance stimulates the nociceptors and if injected subcutaneously it produces pain.
Nerve Growth Factor (NGF)
It is a protein that is in the nervous system , Essential for neurodevelopment and survival.
When inflammation or injury occurs, this substance is released. NGF indirectly activates nociceptors, producing pain. This has also been observed through subcutaneous injections of this substance.
Peptide related to the calcitonin gene (CGRP) and substance P
These substances are also secreted after an injury. Inflammation of an injured tissue also results in the release of these substances, which activates the nociceptors. These peptides also cause vasodilation, which causes the inflammation to expand around the initial damage.
Potassium
A significant correlation was found between the intensity of pain and a higher concentration of extracellular potassium in the injured area. That is, the greater amount of potassium in the extracellular fluid, the more pain is perceived.
Serotonin, acetylcholine, low PH and ATP
All these elements are segregated after damage to the tissues and stimulate the nociceptors producing a sensation of pain.
Lactic acid and muscle spasms
When the muscles are hyperactive or when they do not receive the correct blood flow, the concentration of lactic acid increases, appearing pain. Subcutaneous injections of this substance excite the nociceptors.
Muscle spasms (leading to release of lactic acid) may be the result of certain Headaches .
In summary, when these substances are secreted, the nociceptors are sensitized and reduce their threshold. This effect is called"peripheral sensitization"and is different from the central sensitization, since the latter occurs in the dorsal horn of the spinal cord.
Between about 15 and 30 seconds after an injury, the area of damage (and several centimeters around it) becomes red. This occurs through vasodilation, and leads to inflammation.
This inflammation reaches its maximum level 5 or 10 minutes after the injury, and is accompanied by hyperalgesia (decrease of the pain threshold).
As mentioned, hyperalgesia is an elevated increase in pain sensation in the face of noxious stimuli. This happens for two reasons: after an inflammation nociceptors become more sensitive to pain, lowering their threshold.
At the same time, silent nociceptors are activated. At the end, there is an increase and increase in the persistence of pain.
Pain from the nociceptors to the brain
Nociceptors receive local stimuli and transform them into Action potentials . These are transmitted by the primary sensory fibers to the central nervous system.
The nociceptor fibers have their cell bodies in the Dorsal root ganglia (Later).
The axons that are part of this zone are called afferents because they carry nerve impulses from the periphery of the body to the central nervous system (spinal cord and brain).
These fibers reach the spinal cord through the dorsal root ganglia. Once there, they continue to the gray substance of the posterior horn of the marrow.
The gray substance has 10 different sheets or layers, and each sheet comes different fibers. For example, the A-δ fibers of the skin terminate in sheets I and V; While the fibers C arrive at sheet II, and sometimes at I and III.
Most nociceptive neurons in the spinal cord establish connections with supraspinals, bulbars, and thalamic centers of the brain.
Once there, the pain messages reach the upper brain. The pain has two components, one sensory or discriminative and another emotional or emotional.
The sensory element is captured by the connections of the thalamus with the primary and secondary somatosensory cortex. In turn, these areas send information to the visual, auditory, learning and memory areas.
While in the affective component, information travels from the medial thalamus to areas of the Cortex . Specific Prefrontal areas Such as the supraorbital frontal cortex.
References
- Carlson, N.R. (2006). Physiology of behavior 8ª Ed. Madrid: Pearson.
- Dafny, N. (s.f.). Chapter 6: Pain Principles. Retrieved on March 24, 2017, from Neuroscience online (The University of Texas Health Science Center at Houston): nba.uth.tmc.edu.
- Dubin, A. E., & Patapoutian, A. (2010). Nociceptors: the sensors of the pain pathway. The Journal of Clinical Investigation, 120 (11), 3760-3772.
- FERRANDIZ MACH, M. (s.f.). PHYSIOPATHOLOGY OF PAIN. Retrieved on March 24, 2017, from the Hospital of Santa Creu i Sant Pau. Barcelona: scartd.org.
- Meßlinger, K. (1997). Was ist ein Nozizeptor? Anaesthesist. 46 (2): 142-153.
- Nociceptor. (S.f.). Retrieved on March 24, 2017, from Wikipedia: en.wikipedia.org.