Nociception (also nocioception, from Latin ''nocere'' 'to
harm
Harm is a moral and legal concept.
Bernard Gert construes harm as any of the following:
* pain
* death
* disability
* mortality
* loss of abil ity or freedom
* loss of pleasure.
Joel Feinberg gives an account of harm as setbacks to inte ...
or hurt') is the
sensory nervous system's process of encoding
noxious stimuli A noxious stimulus is a stimulus strong enough to threaten the body’s integrity (i.e. cause damage to tissue). Noxious stimulation induces peripheral afferents responsible for transducing pain (including A-delta and C- nerve fibers, as well as f ...
. It deals with a series of events and processes required for an organism to receive a painful stimulus, convert it to a molecular signal, and recognize and characterize the signal in order to trigger an appropriate defense response.
In nociception, intense chemical (e.g.,
capsaicin
Capsaicin (8-methyl-''N''-vanillyl-6-nonenamide) ( or ) is an active component of chili peppers, which are plants belonging to the genus ''Capsicum''. It is a chemical irritant for mammals, including humans, and produces a sensation of burnin ...
present in
Chili pepper
Chili peppers (also chile, chile pepper, chilli pepper, or chilli), from Nahuatl '' chīlli'' (), are varieties of the berry-fruit of plants from the genus ''Capsicum'', which are members of the nightshade family Solanaceae, cultivated for ...
or
Cayenne pepper
The cayenne pepper is a type of '' Capsicum annuum''. It is usually a moderately hot chili pepper used to flavor dishes. Cayenne peppers are a group of tapering, 10 to 25 cm long, generally skinny, mostly red-colored peppers, often with ...
), mechanical (e.g., cutting, crushing), or thermal (heat and cold) stimulation of
sensory neuron
Sensory neurons, also known as afferent neurons, are neurons in the nervous system, that convert a specific type of stimulus, via their receptors, into action potentials or graded potentials. This process is called sensory transduction. The cel ...
s called
nociceptor
A nociceptor ("pain receptor" from Latin ''nocere'' 'to harm or hurt') is a sensory neuron that responds to damaging or potentially damaging stimuli by sending "possible threat" signals to the spinal cord and the brain. The brain creates the sens ...
s produces a signal that travels along a chain of
nerve fibers via the
spinal cord
The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the sp ...
to the
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...
. Nociception triggers a variety of physiological and behavioral responses to protect the organism against an aggression and usually results in a subjective experience, or
perception
Perception () is the organization, identification, and interpretation of sensory information in order to represent and understand the presented information or environment. All perception involves signals that go through the nervous system ...
, of
pain in
sentient
Sentience is the capacity to experience feelings and sensations. The word was first coined by philosophers in the 1630s for the concept of an ability to feel, derived from Latin '' sentientem'' (a feeling), to distinguish it from the ability to ...
beings.
Detection of noxious stimuli
![Nociceptive pain](https://upload.wikimedia.org/wikipedia/commons/9/91/Nociceptive_pain.jpg)
Potentially damaging mechanical, thermal, and chemical stimuli are detected by nerve endings called
nociceptors, which are found in the
skin
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other animal coverings, such as the arthropod exoskeleton, have different de ...
, on internal surfaces such as the
periosteum
The periosteum is a membrane that covers the outer surface of all bones, except at the articular surfaces (i.e. the parts within a joint space) of long bones. Endosteum lines the inner surface of the medullary cavity of all long bones.
Structu ...
,
joint
A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw- ...
surfaces, and in some internal
organs. Some
nociceptors are unspecialized
free nerve ending
A free nerve ending (FNE) or bare nerve ending, is an unspecialized, afferent nerve fiber sending its signal to a sensory neuron. ''Afferent'' in this case means bringing information from the body's periphery toward the brain. They function as cut ...
s that have their cell bodies outside the
spinal column in the
dorsal root ganglia
A dorsal root ganglion (or spinal ganglion; also known as a posterior root ganglion) is a cluster of neurons (a ganglion) in a dorsal root of a spinal nerve. The cell bodies of sensory neurons known as first-order neurons are located in the dorsal ...
. Other nociceptors rely on specialised structures in the skin to transduce noxious information such as nociceptive
schwann cells
Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory en ...
. Nociceptors are categorized according to the
axon
An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...
s which travel from the receptors to the spinal cord or brain. After nerve injury it is possible for touch fibres that normally carry non-noxious stimuli to be perceived as noxious.
Nociceptive pain consists of an adaptive alarm system. Nociceptors have a certain threshold; that is, they require a minimum intensity of stimulation before they trigger a signal. Once this threshold is reached a signal is passed along the axon of the neuron into the
spinal cord
The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the sp ...
.
Nociceptive threshold testing deliberately applies a noxious stimulus to a
human
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, cultu ...
or animal subject in order to study pain. In animals, the technique is often used to study the efficacy of analgesic drugs and to establish dosing levels and period of effect. After establishing a baseline, the drug under test is given and the elevation in threshold recorded at specified time points. When the drug wears off, the threshold should return to the baseline (pre-treatment) value.
In some conditions, excitation of pain fibers becomes greater as the pain stimulus continues, leading to a condition called
hyperalgesia
Hyperalgesia ( or ; 'hyper' from Greek ὑπέρ (huper, “over”), '-algesia' from Greek algos, ἄλγος (pain)) is an abnormally increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves and can ...
.
Theory
Consequences
Nociception can also cause generalized
autonomic responses before or without reaching consciousness to cause
pallor,
sweating,
tachycardia
Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...
,
hypertension,
lightheadedness
Lightheadedness is a common and typically unpleasant sensation of dizziness or a feeling that one may faint. The sensation of lightheadedness can be short-lived, prolonged, or, rarely, recurring. In addition to dizziness, the individual may feel ...
,
nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
and
fainting
Syncope, commonly known as fainting, or passing out, is a loss of consciousness and muscle strength characterized by a fast onset, short duration, and spontaneous recovery. It is caused by a decrease in blood flow to the brain, typically from ...
.
System overview
This overview discusses
proprioception
Proprioception ( ), also referred to as kinaesthesia (or kinesthesia), is the sense of self-movement, force, and body position. It is sometimes described as the "sixth sense".
Proprioception is mediated by proprioceptors, mechanosensory neurons ...
,
thermoception
Thermoception or thermoreception is the sensation and perception of temperature, or more accurately, temperature differences inferred from heat flux. It deals with a series of events and processes required for an organism to receive a temperature s ...
, chemoception and nociception as they are all integrally connected.
Mechanical
Proprioception is determined by using standard mechanoreceptors (especially
ruffini corpuscle
The Bulbous corpuscle or Ruffini ending or Ruffini corpuscle is a slowly adapting mechanoreceptor located in the cutaneous tissue between the dermal papillae and the hypodermis. It is named after Angelo Ruffini
Angelo Ruffini (Pretare of Arquata ...
s (stretch) and
transient receptor potential (TRP) channels). Proprioception is completely covered within the
somatosensory system
In physiology, the somatosensory system is the network of neural structures in the brain and body that produce the perception of touch (haptic perception), as well as temperature (thermoception), body position (proprioception), and pain. It ...
as the brain processes them together.
Thermoception refers to stimuli of moderate temperatures
, as anything beyond that range is considered pain and moderated by nociceptors. TRP and potassium channels
RPM (1-8), TRPV (1-6), TRAAK, and TREKeach respond to different temperatures (among other stimuli) which create action potentials in nerves which join the mechano (touch) system in the posterolateral tract. Thermoception, like proprioception, is then covered by the somatosensory system.
TRP channels that detect noxious stimuli (mechanical, thermal, and chemical pain) relay that info to nociceptors that generate an action potential. Mechanical TRP channels react to depression of their cells (like touch), thermal TRP change shape in different temperatures, and chemical TRP act like
taste bud
Taste buds contain the taste receptor cells, which are also known as gustatory cells. The taste receptors are located around the small structures known as papillae found on the upper surface of the tongue, soft palate, upper esophagus, the c ...
s, signalling if their receptors bond to certain elements/chemicals.
Neural
*
Laminae 3-5 make up
nucleus proprius in spinal grey matter.
*
Lamina 2 makes up
substantia gelatinosa of Rolando
The apex of the posterior grey column, one of the three grey columns of the spinal cord, is capped by a V-shaped or crescentic mass of translucent, gelatinous neuroglia, termed the substantia gelatinosa of Rolando (or SGR) (or gelatinous substance ...
, unmyelinated spinal grey matter. Substantia receives input from nucleus proprius and conveys intense, poorly localized pain.
*
Lamina 1 primarily project to the
parabrachial area and
periaqueductal grey
The periaqueductal gray (PAG, also known as the central gray) is a brain region that plays a critical role in autonomic function, motivated behavior and behavioural responses to threatening stimuli. PAG is also the primary control center for d ...
, which begins the suppression of pain via neural and hormonal inhibition. Lamina 1 receive input from thermoreceptors via the
posterolateral tract
The posterolateral tract (fasciculus of Lissauer, Lissauer's tract, tract of Lissauer, dorsolateral fasciculus, dorsolateral tract, zone of Lissauer) is a small strand situated in relation to the tip of the posterior column close to the entrance of ...
. Marginal nucleus of the spinal cord are the only unsuppressible pain signals.
* The
parabrachial area integrates taste and pain info, then relays it. Parabrachial checks if the pain is being received in normal temperatures and if the
gustatory system
The gustatory system or sense of taste is the sensory system that is partially responsible for the perception of taste (flavor). Taste is the perception produced or stimulated when a substance in the mouth reacts chemically with taste receptor ...
is active; if both are so the pain is assumed to be due to poison.
*
Ao fibers synapse on laminae 1 and 5 while
Ab synapses on 1, 3, 5, and C.
C fiber
Group C nerve fibers are one of three classes of nerve fiber in the central nervous system (CNS) and peripheral nervous system (PNS). The C group fibers are unmyelinated and have a small diameter and low conduction velocity, whereas Groups A a ...
s exclusively synapse on lamina 2.
* The
amygdala
The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex verte ...
and
hippocampus
The hippocampus (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, ...
create and encode the memory and emotion due to pain stimuli.
* The
hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
signals for the release of hormones that make pain suppression more effective; some of these are sex hormones.
*
Periaqueductal grey
The periaqueductal gray (PAG, also known as the central gray) is a brain region that plays a critical role in autonomic function, motivated behavior and behavioural responses to threatening stimuli. PAG is also the primary control center for d ...
(with hypothalamic hormone aid) hormonally signals
reticular formation’s
raphe nuclei to produce
serotonin that inhibits laminae pain nuclei.
*
*
Lateral spinothalamic tract
The spinothalamic tract is a part of the anterolateral system or the ventrolateral system, a sensory pathway to the thalamus. From the ventral posterolateral nucleus in the thalamus, sensory information is relayed upward to the somatosensory cor ...
aids in localization of pain.
*
Spinoreticular and
spinotectal tracts are merely relay tracts to the
thalamus
The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...
that aid in the perception of pain and alertness towards it. Fibers cross over (left becomes right) via the spinal
anterior white commissure
The anterior white commissure (ventral white commissure) is a bundle of nerve fibers which cross the midline of the spinal cord just anterior (in front of) to the gray commissure ( Rexed lamina X). A delta fibers (Aδ fibers) and C fibers carryi ...
.
*
Lateral lemniscus
The lateral lemniscus is a tract of axons in the brainstem that carries information about sound from the cochlear nucleus to various brainstem nuclei and ultimately the contralateral inferior colliculus of the midbrain. Three distinct, primarily ...
is the first point of integration of sound and pain information.
*
Inferior colliculus
The inferior colliculus (IC) (Latin for ''lower hill'') is the principal midbrain nucleus of the auditory pathway and receives input from several peripheral brainstem nuclei in the auditory pathway, as well as inputs from the auditory cortex. T ...
(IC) aids in sound orienting to pain stimuli.
*
Superior colliculus receives IC’s input, integrates visual orienting info, and uses the balance topographical map to orient the body to the pain stimuli.
*
Inferior cerebellar peduncle
The upper part of the posterior district of the medulla oblongata is occupied by the inferior cerebellar peduncle, a thick rope-like strand situated between the lower part of the fourth ventricle and the roots of the glossopharyngeal and vagus nerv ...
integrates proprioceptive info and outputs to the
vestibulocerebellum. The peduncle is not part of the lateral-spinothalamic-tract-pathway; the medulla receives the info and passes it onto the peduncle from elsewhere (see
somatosensory system
In physiology, the somatosensory system is the network of neural structures in the brain and body that produce the perception of touch (haptic perception), as well as temperature (thermoception), body position (proprioception), and pain. It ...
).
* The
thalamus
The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...
is where pain is thought to be brought into
perception
Perception () is the organization, identification, and interpretation of sensory information in order to represent and understand the presented information or environment. All perception involves signals that go through the nervous system ...
; it also aids in pain suppression and modulation, acting like a
bouncer
A bouncer (also known as a doorman or door supervisor) is a type of security guard, employed at venues such as bars, nightclubs, cabaret clubs, stripclubs, casinos, hotels, billiard halls, restaurants, sporting events, schools, concerts, or ...
, allowing certain intensities through to the cerebrum and rejecting others.
* The
somatosensory cortex
In physiology, the somatosensory system is the network of neural structures in the brain and body that produce the perception of touch ( haptic perception), as well as temperature (thermoception), body position (proprioception), and pain. It i ...
decodes nociceptor info to determine the exact location of pain and is where proprioception is brought into consciousness; inferior cerebellar peduncle is all unconscious proprioception.
*
Insula judges the intensity of the pain and provides the ability to imagine pain.
*
Cingulate cortex is presumed to be the memory hub for pain.
In non-mammalian animals
Nociception has been documented in non-mammalian animals, including fish and a wide range of
invertebrates
Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordat ...
, including leeches, nematode worms, sea slugs, and fruit flies. As in mammals, nociceptive neurons in these species are typically characterized by responding preferentially to high
temperature
Temperature is a physical quantity that expresses quantitatively the perceptions of hotness and coldness. Temperature is measurement, measured with a thermometer.
Thermometers are calibrated in various Conversion of units of temperature, temp ...
(40° Celsius or more), low pH, capsaicin, and tissue damage.
History of term
The term "nociception" was coined by
Charles Scott Sherrington
Sir Charles Scott Sherrington (27 November 1857 – 4 March 1952) was an eminent English neurophysiologist. His experimental research established many aspects of contemporary neuroscience, including the concept of the spinal reflex as a system ...
to distinguish the physiological process (nervous activity) from pain (a subjective experience).
It is derived from the Latin verb "''nocēre''", which means "to harm".
See also
*
*
*
*
References
{{pain
Pain
Sensory systems
Acute pain