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The gate control theory of
pain Pain is a distressing feeling often caused by intense or damaging Stimulus (physiology), stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sense, sensory and emotional experience associated with, or res ...
asserts that non-painful input closes the nerve "gates" to painful input, which prevents pain sensation from traveling to the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...
. The gate control theory of pain describes how non-painful sensations can override and reduce painful sensations. A painful, nociceptive stimulus stimulates primary afferent fibers and travels to the brain via transmission cells. Increasing activity of the transmission cells results in increased perceived pain. Conversely, decreasing activity of transmission cells reduces perceived pain. In the gate control theory, a closed "gate" describes when input to transmission cells is blocked, therefore reducing the sensation of pain. An open “gate” describes when input to transmission cells is permitted, therefore allowing the sensation of pain. First proposed in 1965 by Ronald Melzack and Patrick Wall, the theory offers a physiological explanation for the previously observed effect of psychology on pain perception. Combining early concepts derived from the specificity theory and the peripheral pattern theory, the gate control theory is considered to be one of the most influential theories of pain. This theory provided a neural basis which reconciled the specificity and pattern theories -- and ultimately revolutionized pain research. Although there are some important observations that the gate control theory cannot explain adequately, this theory remains the theory of pain which most accurately accounts for the physical and psychological aspects of pain perception. Willem Noordenbos (1910–1990), a Dutch researcher at the
University of Amsterdam The University of Amsterdam (abbreviated as UvA, ) is a public university, public research university located in Amsterdam, Netherlands. Established in 1632 by municipal authorities, it is the fourth-oldest academic institution in the Netherlan ...
, proposed in 1959 a model which featured interaction between small (unmyelinated) and thick (myelinated) fibers. In this model, the fast (myelinated) fibers block the slow (unmyelinated) fibers: "fast blocks slow".


Proposed mechanisms

When you experience a negative feeling, such as pain from a bump or an itch from a bug bite, a common reaction is an attempt to eliminate the feeling by rubbing the painful bump or scratching the itchy bite. Gate control theory asserts that activation of nerves that do not transmit pain signals, called nonnociceptive fibers, can interfere with signals from pain fibers, thereby inhibiting pain. It is proposed that both small-diameter (pain-transmitting) and large-diameter (touch-, pressure-, and vibration- transmitting) afferent nerve fibers carry information from the site of the injury to two destinations in the dorsal horn: 1. Transmission Cells that carry the pain signal up to the brain, and 2. Inhibitory Interneurons that impede transmission cell activity. Activation of transmission cells occurs from both excitatory small-diameter and excitatory large-diameter fibers. However, activation of the inhibitory interneurons varies: large-diameter fibers excite the interneuron, which ultimately reduces transmission cell firing, whereas small-diameter fibers inhibit the inhibitory interneuron which lessens the inhibitory input to the transmission cell. Therefore, less pain is felt (via reduced transmission cell activity) when more activity in large-diameter fibers (touch-, pressure-, and vibration- transmitting) occurs relative to the activity in small-diameter (pain-transmitting) fibers. The
peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of Bilateria, bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside t ...
has centers at which pain stimuli can be regulated. Some areas in the dorsal horn of the
spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...
that are involved in receiving pain stimuli from Aδ and C fibers, called
lamina Lamina may refer to: People * Saa Emerson Lamina, Sierra Leonean politician * Tamba Lamina, Sierra Leonean politician and diplomat Science and technology * Planar lamina, a two-dimensional planar closed surface with mass and density, in mathem ...
e, also receive input from Aβ fibers. The nonnociceptive fibers indirectly inhibit the effects of the pain fibers, 'closing a gate' to the transmission of their stimuli. In other parts of the laminae, pain fibers also inhibit the effects of nonnociceptive fibers, 'opening the gate'. This presynaptic inhibition of the dorsal nerve endings can occur through specific types of GABAA receptors (not through the α1 GABAA receptor and not through the activation of glycine receptors which are also absent from these types of terminals). Thus, certain GABAA receptor subtypes but not glycine receptors can presynaptically regulate
nociception In physiology, nociception , also nocioception; ) is the Somatosensory system, sensory nervous system's process of encoding Noxious stimulus, noxious stimuli. It deals with a series of events and processes required for an organism to receive a pai ...
and
pain Pain is a distressing feeling often caused by intense or damaging Stimulus (physiology), stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sense, sensory and emotional experience associated with, or res ...
transmission. An inhibitory connection may exist with Aβ and C fibers, which may form a
synapse In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...
on the same projection neuron. The same neurons may also form synapses with an inhibitory interneuron that also synapses on the projection neuron, reducing the chance that the latter will fire and transmit pain stimuli to the
brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...
(image on the right). The inhibitory interneuron fires spontaneously. The C fiber's synapse would inhibit the inhibitory interneuron, indirectly increasing the projection neuron's chance of firing. The Aβ fiber, on the other hand, forms an ''excitatory'' connection with the inhibitory interneuron, thus ''decreasing'' the projection neuron's chance of firing (like the C fiber, the Aβ fiber also has an excitatory connection on the projection neuron itself). Thus, depending on the relative rates of firing of C and Aβ fibers, the firing of the nonnociceptive fiber may inhibit the firing of the projection neuron and the transmission of pain stimuli.


History and legacy

Gate control theory asserts that activation of nerves which do not transmit pain signals, called nonnociceptive fibers, can interfere with signals from pain fibers, thereby inhibiting pain. Afferent pain-receptive nerves, those that bring signals to the brain, comprise at least two kinds of fibers - a fast, relatively thick,
myelin Myelin Sheath ( ) is a lipid-rich material that in most vertebrates surrounds the axons of neurons to insulate them and increase the rate at which electrical impulses (called action potentials) pass along the axon. The myelinated axon can be lik ...
ated "Aδ" fiber that carries messages quickly with intense pain, and a small, unmyelinated, slow "C" fiber that carries the longer-term throbbing and
chronic pain Chronic pain is pain that persists or recurs for longer than 3 months.https://icd.who.int/browse/2025-01/mms/en#1581976053 It is also known as gradual burning pain, electrical pain, throbbing pain, and nauseating pain. This type of pain is in cont ...
. Large-diameter Aβ fibers are nonnociceptive (do not transmit pain stimuli) and inhibit the effects of firing by Aδ and C fibers. When it was first proposed in 1965, the theory was met with considerable skepticism. Despite having to undergo several modifications, its basic conception remains unchanged. Ronald Melzack and Patrick Wall introduced their "gate control" theory of pain in the 1965 ''Science'' article "Pain Mechanisms: A New Theory". The authors proposed that both thin (pain) and large diameter (touch, pressure, vibration) nerve fibers carry information from the site of injury to two destinations in the spinal cord: transmission cells that carry the pain signal up to the brain, and inhibitory interneurons that impede transmission cell activity. Activity in both thin and large diameter fibers ''excites'' transmission cells. Thin fiber activity ''impedes'' the inhibitory cells (tending to allow the transmission cell to fire) and large diameter fiber activity ''excites'' the inhibitory cells (tending to inhibit transmission cell activity). So, the more large fiber (touch, pressure, vibration) activity relative to thin fiber activity at the inhibitory cell, the less pain is felt. The authors had drawn a neural "circuit diagram" to explain why we rub a smack. They pictured not only a signal traveling from the site of injury to the inhibitory and transmission cells and up the spinal cord to the brain, but also a signal traveling from the site of injury directly up the cord to the brain (bypassing the inhibitory and transmission cells) where, depending on the state of the brain, it may trigger a signal back down the spinal cord to modulate inhibitory cell activity (and so pain intensity). The theory offered a physiological explanation for the previously observed effect of psychology on pain perception. In 1968, three years after the introduction of the gate control theory, Ronald Melzack concluded that pain is a multidimensional complex with numerous sensory, affective, cognitive, and evaluative components. Melzack's description has been adapted by the International Association for the Study of Pain in a contemporary definition of pain. Despite flaws in its presentation of neural architecture, the theory of gate control is currently the only theory that most accurately accounts for the physical and psychological aspects of pain. The gate control theory attempted to end a century-old debate about whether pain is represented by specific neural elements (specificity theory) or by patterned activity (pattern theory) within a convergent somatosensory subsystem. Although it is now considered to be oversimplified with flaws in the presentation of neural architecture, the gate control theory spurred many studies in pain research and significantly advanced our understanding of pain.


Therapeutic uses

The mechanism of gate control theory can be used therapeutically. Gate control theory thus explains how stimulus that activates only nonnociceptive nerves can inhibit pain. The pain seems to be lessened when the area is rubbed because activation of nonnociceptive fibers inhibits the firing of nociceptive ones in the laminae. In transcutaneous electrical nerve stimulation (TENS), nonnociceptive fibers are selectively stimulated with mild electrical currents through
electrode An electrode is an electrical conductor used to make contact with a nonmetallic part of a circuit (e.g. a semiconductor, an electrolyte, a vacuum or a gas). In electrochemical cells, electrodes are essential parts that can consist of a varie ...
s in order to produce this effect and thereby lessen pain. One area of the brain involved in reduction of pain sensation is the periaqueductal gray matter that surrounds the
third ventricle The third ventricle is one of the four connected cerebral ventricles of the ventricular system within the mammalian brain. It is a slit-like cavity formed in the diencephalon between the two thalami, in the midline between the right and lef ...
and the cerebral aqueduct of the
ventricular system In neuroanatomy, the ventricular system is a set of four interconnected cavities known as cerebral ventricles in the brain. Within each ventricle is a region of choroid plexus which produces the circulating cerebrospinal fluid (CSF). The ventric ...
. Stimulation of this area produces
analgesia Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professionals ...
(but not total numbing) by activating descending pathways that directly and indirectly inhibit nociceptors in the laminae of the spinal cord. Descending pathways also activate
opioid Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...
receptor-containing parts of the spinal cord. Afferent pathways interfere with each other constructively, so that the brain can control the degree of pain that is perceived, based on which pain stimuli are to be ignored to pursue potential gains. The brain determines which stimuli are profitable to ignore over time. Thus, the brain controls the perception of pain quite directly, and can be "trained" to turn off forms of pain that are not "useful". This understanding led Melzack to assert that ''pain is in the brain''. Gate control theory influenced the development of mindfulness-based pain management (MBPM).


See also

* Tactile induced analgesia *
Neuromatrix NeuroMatrix is a digital signal processor (DSP) series developed by NTC Module. The DSP has a VLIW/SIMD architecture. It consists of a 32-bit Reduced instruction set computing, RISC core and a 64-bit vector co-processor. The vector co-processor su ...


References

{{reflist Pain