Can understanding how nociceptors function and their role in processing pain signals help individuals who are managing injuries and/or living with chronic pain conditions?
Nociceptors
Nociceptors are nerve endings that detect harmful stimuli, such as extreme temperatures, pressure, and chemicals, and signal pain. They are the body’s first defense against potentially damaging environmental inputs.
Nociceptors are in the skin, muscles, joints, bones, internal organs, deep tissues, and cornea.
They detect harmful stimuli and convert them into electrical signals.
These signals are sent to the brain’s higher centers.
The brain interprets the signals as pain, which prompts the body to avoid the harmful stimulus.
Nociceptors, often called pain receptors, are free nerve endings all over the body. They play a pivotal role in how the body feels and reacts to pain. The main purpose of a nociceptor is to respond to damage to the body by transmitting signals to the spinal cord and brain. (Purves D, Augustine GJ, Fitzpatrick D, et al., editors. 2001) If you bang your foot, the nociceptors on the skin are activated, sending a signal to the brain via the peripheral nerves to the spinal cord. Pain resulting from any cause is transmitted this way. Pain signals are complex, carrying information about the stimuli’s location and intensity. This causes the brain to fully process the pain and send communication back to block further pain signals.
Thermal nociceptors respond to extreme hot or cold temperatures.
For instance, when touching a hot stove, the nociceptors, which signal pain, are activated immediately, sometimes before you know what you’ve done.
Mechanical
Mechanical nociceptors respond to intense stretching or strain, such as pulling a hamstring or straining a tendon.
The muscles or tendons are stretched beyond their ability, stimulating nociceptors and sending pain signals to the brain.
Chemical
Chemical nociceptors respond to chemicals released from tissue damage.
For example, prostaglandins and substance P or external chemicals like topical capsaicin pain creams.
Silent
Silent nociceptors must be first activated by tissue inflammation before responding to a mechanical, thermal, or chemical stimulus.
Most visceral nociceptors are located on organs in the body.
Polymodal
Polymodal nociceptors respond to mechanical, thermal, and chemical stimuli.
Mechano-thermal
Mechano-thermal nociceptors respond to mechanical and thermal stimuli.
Pain Transmission
Nociceptors are also classified by how fast they transmit pain signals. Transmission speed is determined by the type of nerve fiber known as an axon a nociceptor has. There are two main types.
The first type is A fiber axon, fibers surrounded by a fatty, protective sheath called myelin.
Myelin allows nerve signals/action potentials to travel rapidly.
Because of the difference in transmission speed, the pain signals from the A fibers reach the spinal cord first. As a result, after an acute injury, an individual experiences pain in two phases, one from the A fibers and one from the C fibers. (Ngassapa D. N. 1996)
Pain Perception Phases
When an injury occurs, the stimulated nociceptors activate the A fibers, causing a person to experience sharp, prickling pain.
This is the first phase of pain, known as fast pain, because it is not especially intense but comes right after the stimulus.
During the second phase of pain, the C fibers are activated, causing an intense, burning pain that persists even after the stimulus has stopped.
The fact that the C fibers carry burning pain explains why there is a short delay before feeling the sensation.
The C fibers also carry aching, sore pain caused by organs within the body, such as a sore muscle or stomachache. (Ngassapa D. N. 1996)
Injury Medical Chiropractic and Functional Medicine Clinic
Injury Medical Chiropractic and Functional Medicine Clinic works with primary healthcare providers and specialists to build optimal health and wellness solutions. We focus on what works for you to relieve pain, restore function, prevent injury, and help mitigate issues through adjustments that help the body realign itself. They can also work with other medical professionals to integrate a treatment plan to resolve musculoskeletal problems.
From Injury To Recovery With Chiropractic Care
References
Purves D, A. G., Fitzpatrick D, et al., editors. (2001). Nociceptors. In Neuroscience. 2nd edition. (2nd ed.). Sunderland (MA): Sinauer Associates. https://www.ncbi.nlm.nih.gov/books/NBK10965/
University of Texas McGovern Medical School. (2020). Chapter 6: Pain Principles. https://nba.uth.tmc.edu/neuroscience/m/s2/chapter06.html
Ngassapa D. N. (1996). Comparison of functional characteristics of intradental A- and C-nerve fibres in dental pain. East African medical journal, 73(3), 207–209.
Glutamate is the main excitatory neurotransmitter in the central nervous system, or CNS, of mammals and it primarily interacts with both metabotropic and ionotropic receptors to activate and regulate postsynaptic responses. Both AMPA and NMDA receptors are fundamental mediators of synaptic plasticity, the ability of synapses to strengthen or weaken, where dysregulation of those receptors leads to neurodegeneration in a variety of disorders, including Alzheimer’s disease. �
The main difference between AMPA and NMDA receptors is that sodium and potassium increases in AMPA receptors where calcium increases along with sodium and potassium influx in NMDA receptors. Moreover, AMPA receptors do not have a magnesium ion block while NMDA receptors do have a calcium ion block. AMPA and NMDA are two types of ionotropic, glutamate receptors. They are non-selective, ligand-gated ion channels, which mainly enable the passage of sodium and potassium ions. Furthermore, glutamate is a neurotransmitter which creates excitatory postsynaptic signals in the CNS. �
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What are AMPA Receptors?
AMPA, also known as ?-amino-3-hydroxy-5-methyl-4-isoxazole-propionate, receptors are glutamate receptors which are in charge of maintaining the rapid, synaptic transmission in the central nervous system. AMPA receptors have four subunits, GluA1-4. Moreover, the GluA2 subunit is not permeable to calcium ions because it contains arginine from the TMII region. �
Furthermore, AMPA receptors are involved in the transmission of the majority of the rapid, excitatory synaptic signals. The increase of the post-synaptic response depends on the amount of receptors in the post-synaptic surface. The type of agonist which activates the AMPA receptors is ?-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid. The activation of the AMPA receptors leads to the non-selective transportation of cations, such as sodium and potassium ions, into the cell. This generates an action potential in the postsynaptic membrane. Figure 1 below demonstrates a diagram of AMPA receptors. �
What are NMDA Receptors?
NMDA, also known as N-methyl-d-aspartate, receptors are glutamate receptors which are found in the postsynaptic membrane. The NMDA receptors are made up of two varieties of subunits: GluN1 and GluN2. The GluN1 subunit is fundamental for the role of the receptor. This subunit can associate with one of the four types of GluN2 subunits, GluN2A-D. �
Furthermore, the main utilization of the NMDA receptors is to maintain the synaptic response. In the resting membrane potential, these receptors are inactive due to the creation of a magnesium block. The agonist of the NMDA receptor is N-methyl-d-aspartic acid. L-glutamate, including glycine, can connect to the receptor to activate it. Upon stimulation, NMDA receptors activate the calcium influx along with the potassium and sodium influx. Figure 2 demonstrates NMDA receptors. �
Similarities Between AMPA and NMDA Receptors
AMPA, NMDA, and kainate receptors are the three main types of glutamate receptors.
These are ligand-gated ion channels which activate and regulate sodium and potassium ions.
These are known due to the type of agonist which activates the receptor.
Moreover, the activation of these receptors produces excitatory postsynaptic responses or ESPSs.
Furthermore, several protein subunits connect together to form these receptors.
Difference Between AMPA and NMDA Receptors
AMPA receptors are best known as a type of glutamate receptor which activates in excitatory neurotransmission and connects ?-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid which additionally works as a cation channel. Where the NMDA receptors are best known as a type of glutamate receptor which helps in excitatory neurotransmission and also connects N-methyl-D-aspartate. This is the most fundamental difference between AMPA and NMDA receptors. �
AMPA receptors have four subunits, GluA1-4 while NMDA receptors have a GluN1 subunit associated with one of the four GluN2 receptors, GluN2A-D. Activation can also be a difference between AMPA and NMDA receptors. AMPA receptors are only activated by glutamate while NMDA receptors are activated by different agonists. The agonist for AMPA receptors is ?-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid where the agonist for NMDA receptors is N-methyl-d-aspartic acid. �
Ion influx is a fundamental difference between AMPA and NMDA receptors. Activation of AMPA receptors results in the sodium and potassium influx while the activation of NMDA receptors leads to an increase in potassium, sodium, and calcium. Another distinction between AMPA and NMDA receptors is that AMPA receptors do not contain a calcium ion where NMDA receptors contain magnesium receptors. Also, AMPA receptors are responsible for the transmission of the majority of the rapid, excitatory synaptic signals while NMDA receptors are responsible for the modulation of the synaptic response. �
AMPA receptors are glutamate receptors which lead to the influx of sodium and potassium ions. NMDA receptors are another type of glutamate receptors which result in the influx of calcium ions with potassium and sodium ions. The main difference between AMPA and NMDA receptors is the type of ion influx associated with their activation and regulation. �
Several varieties of ionotropic glutamate receptors have been demonstrated in the following article. Three of these main excitatory neurotransmitter in the central nervous system, or CNS, are ligand-gated ion channels best known as AMPA receptors, NMDA receptors, and kainate receptors. These ionotropic glutamate receptors are best referred to after the agonists which activate and regulate them: AMPA or ?-amino-3-hydroxy-5-methyl-4-isoxazole-propionate, NMDA or N-methyl-d-aspartate, and kainic acid. – Dr. Alex Jimenez D.C., C.C.S.T. Insight
The purpose of the article above is to demonstrate the difference between AMPA and NMDA receptors for brain health. Neurological diseases are associated with the brain, the spine, and the nerves. The scope of our information is limited to chiropractic, musculoskeletal and nervous health issues as well as functional medicine articles, topics, and discussions. To further discuss the subject matter above, please feel free to ask Dr. Alex Jimenez or contact us at 915-850-0900 . �
Curated by Dr. Alex Jimenez �
Additional Topic Discussion: Chronic Pain
Sudden pain is a natural response of the nervous system which helps to demonstrate possible injury. By way of instance, pain signals travel from an injured region through the nerves and spinal cord to the brain. Pain is generally less severe as the injury heals, however, chronic pain is different than the average type of pain. With chronic pain, the human body will continue sending pain signals to the brain, regardless if the injury has healed. Chronic pain can last for several weeks to even several years. Chronic pain can tremendously affect a patient’s mobility and it can reduce flexibility, strength, and endurance.
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El Paso, TX. Chiropractor, Dr. Alexander Jimenez continues the discussion on the anatomy of nerve fibers, receptors, spinal tracts and brain pathway/s. As the spinal nerve nears the spinal cord, it splits into the dorsal and ventral roots. The dorsal root only contains the axons of sensory neurons. While the ventral roots contain only the axons of motor neurons. Some of the branches synapse with local neurons in the dorsal root ganglion, posterior (dorsal) horn, and even the anterior (ventral) horn, at the spine where they enter.
Other branches travel short distances up or down the spine to interact with neurons at other levels of the spinal cord. A branch can also turn into the posterior (dorsal) column white matter to connect with the brain. Spinal nerve systems that connect to the brain are contralateral, in that the right side of the body is connected to the left side of the brain and the left side of the body is connected to the right side of the brain.
Cranial nerves convey specific sense information from the head and neck directly to the brain. Whereas spinal information is contralateral, cranial nerve systems are for the most part�ipsilateral, meaning that a cranial nerve on the right side of the head is connected to the right side of the brain. Some cranial nerves contain only sensory axons. Other cranial nerves have both sensory and motor axons, including the trigeminal, facial and glossopharyngeal. General senses of somatosensation for the face travel through the trigeminal system.
PATHWAYS
THE POSTERIOR COLUMN� MEDIAL LEMNISCUS SYSTEM CONVEYS INFORMATION ABOUT TOUCH AND LIMB POSITION
POSTERIOR COLUMN MEDIAL LEMNISCAL PATHWAY
The term posterior column refers to the entire contents of a posterior funiculus, exclusive of its share of the propriospinal tract. The posterior columns consist mainly of ascending collaterals of large myelinated primary afferents carrying impulses from various kinds of mechanoreceptors (although substantial numbers of second-order fibers and unmyelinated fibers are also included). This has traditionally been considered the major pathway by which information from low-threshold cutaneous, joint, and muscle receptors reaches the cerebral cortex.
2-Minute Neuroscience: Touch & The Dorsal Columns-Medial Lemniscus
DAMAGE TO THE POSTERIOR COLUMN�MEDIAL LEMNISCUS SYSTEM CAUSES IMPAIRMENT OF PROPRIOCEPTION AND DISCRIMINATIVE TACTILE FUNCTIONS
�As might be expected from the types of afferents contained in the posterior columns, this pathway carries information important for the conscious appreciation of touch, pressure, and vibration and of joint position and movement. However, because input from cutaneous receptors also reaches the cortex by other routes, damage to the posterior columns causes impairment, but not abolition, of tactile perception. Complex discrimination tasks are more severely affected than is the simple detection of stimuli. Other functions, such as proprioception and kinesthesia, are classically considered to be totally lost after posterior column destruction. The result is a distinctive type of ataxia (incoordination of movement); the brain is unable to direct motor activity properly without sensory feedback about the current position of parts of the body. This ataxia is particularly pronounced when the patient�s eyes are closed, preventing visual compensation.�
Given the role of the posterior column, the patient should be screened for any abnormalities regarding their sense of fine touch, vibration, barognosis, graphesthesia, stereognosis, kinaesthesia, two-point discrimination and conscious proprioception:
A common way of testing for fine touch is to ask the patient to recognize common objects placed within a cloth using their touch.
Vibration sense can be tested using a low pitched C128 tuning fork placed along a bony prominence of the desired corresponding spinal level(s) to be tested.
Barognosis refers to the ability to determine the approximate weight of an object.
Graphesthesia refers to the ability to recognize writing on the skin by touch. The practitioner can draw out a letter on the patients skin as a way of testing.
Kinaesthesia refers to ones own sense of body motion (excluding equilibrium which is controlled in part by the inner ear) and is commonly tested using the subject�s ability to detect an externally imposed passive movement, or the ability to reposition a joint to a predetermined position.
Proprioception is often assessed using the Rombergs test. This examination is based on the notion that a person requires at least two of the three following senses to maintain balance while standing: proprioception; vestibular function and vision. A patient who has a defect within their proprioceptive mechanism can still maintain balance by using vestibular function and vision. In the Romberg test, the patient is stood up and asked to close their eyes. A loss of balance is interpreted as a positive Romberg sign.
THE SPINOTHALAMIC TRACT CONVEYS INFORMATION ABOUT PAIN AND TEMPERATURE
A GOOD BRAIN CAN MODULATE PAIN
SPINOTHALAMIC TRACT
Pain is a complex sensation, in that a noxious stimulus leads not only to the perception of where it occurred but also to things such as a rapid increase in level of attention, emotional reactions, autonomic responses, and a greater likelihood that the event and its circumstances will be remembered. Corresponding to this complexity, multiple pathways convey nociceptive information rostrally from the spinal cord. One of them (the spinothalamic tract) is analogous to the posterior column�medial lemniscus pathway.
SPINOTHALAMIC TRACTS
Two main parts of the Spinothalamic Tract (STT)
Lateral Spinothalamic Tract
Transmission of pain and temperature
Anterior Spinothalamic Tract
Transmission of crude touch and firm pressure
DAMAGE TO THE ANTEROLATERAL SYSTEM CAUSES DIMINUTION OF PAIN AND TEMPERATURE SENSATIONS
Examination:
Given the role of the spinothalamic tract, the patient should be screened for any abnormalities regarding their sense of touch, pain, temperature, and pressure sensation.
Screening for such abnormalities is commonly done using gentle pin pricks and cotton wool, to contrast between sharp and soft, following cutaneous sensory nerve root distributions. Hot and cold discrimination can be ascertained using the cold metal arm of a tuning fork, and a warm palm or heated object.
2 Minute Neuroscience: Pain & The Anterolateral System
HAUSER ET AL. FIBROMYALGIA, 2015
�Pain processing and its modulation: Activation of peripheral pain receptors (also called nociceptors) by noxious stimuli generates signals that travel to the dorsal horn of the spinal cord via the dorsal root ganglion. From the dorsal horn, the signals are carried along the ascending pain pathway or the spinothalamic tract to the thalamus and the cortex. Pain can be controlled by nociception- inhibiting and nociception-facilitating neurons. Descending signals originating in the supraspinal centers can modulate activity in the dorsal horn by controlling spinal pain transmission. CNS, central nervous system.�
SPINAL INFORMATION REACHES THE CEREBELLUM BOTH DIRECTLY AND INDIRECTLY
The spinal cord is an important source of information used by the cerebellum in the coordination of movement. This information reaches the cerebellar cortex and nuclei both directly, by way of spinocerebellar tracts, and indirectly, by way of relays in brainstem nuclei. A number of spinocerebellar tracts have been described, some representing the upper extremity and others the lower extremity. Only three have been well characterized.
Ascending Tracts | Spinocerebellar Tract
DESCENDING PATHWAYS INFLUENCE THE ACTIVITY OF LOWER MOTOR NEURONS
El Paso, TX. Chiropractor, Dr. Alexander Jimenez discusses the anatomy of nerve fibers, receptors, spinal tracts and brain pathways. Regions of the Central Nervous System (CNS) coordinate various somatic processes using sensory inputs and motor outputs of peripheral nerves. Important areas of the CNS that play a role in somatic processes are separated in the spinal cord brain stem. Sensory pathways that carry peripheral sensations to the brain are referred to an ascending pathway, or tract. Various sensory modalities follow specific pathways through the CNS. Somatosensory stimuli activate receptors in the skin, muscles, tendons, and joints throughout the entire body. The somatosensory pathways are divided into two separate systems based on the location of the receptor neurons. Somatosensory stimuli from below the neck run along the sensory pathways of the spinal cord, and the somatosensory stimuli from the head and neck travel through cranial nerves.
ANATOMY OF RECEPTORS, NERVE FIBERS, SPINAL CORD TRACTS AND BRAINSTEM PATHWAYS
RECEPTORS AND RECEPTOR BASED THERAPY
NEURONS NEED THREE THINGS TO SURVIVE!
FUNCTIONAL NEUROLOGY KEY CONCEPTS
The cell needs three things to survive.
Oxygen, glucose and stimulation.
Stimulation = Chiropractic, exercise, etc.
Stimulation leads to neuronal growth
Neuronal growth leads to plasticity
Subluxations alter the frequency of firing of neurons
Activation of one side will stimulate ipsilateral cerebellum and contralateral cortex (usually)
Proper stimulation CAN reduce pain.
CHIROPRACTIC IS RECEPTOR-BASED THERAPY
INTRODUCTION
The ongoing activity and output of the CNS are greatly influenced, and sometimes more or less determined, by incoming sensory information.
The basis of this incoming sensory information is an array of sensory receptors, cells that detect various stimuli and produce receptor potentials in response, often with astonishing effectiveness.
The health of the neuron, however, plays a huge role in how neurons can produce receptor potentials, the endurance of the neuron and the ability to create plasticity.
�Neurons that fire together, wire together.� Hebbian Theory
TYPES OF RECEPTORS
Chemoreceptors
Smell, taste, interoceptors
Thermoreceptors
Temperature
Mechanoreceptors
Cutaneous receptors for touch, auditory, vestibular, proprioceptors
Nociceptors
Pain
PARTS OF RECEPTORS
Although their morphologies vary widely, all receptors have three general parts:
1. Receptive Area 2. Area Rich In Mitochondria
Health of the neurons within the receptors will determine its response to stimulation
3. Synaptic Area To Pass Messages To The CNS
RECEPTIVE FIELDS
These are particular areas in the periphery where application of an adequate stimulus causes the receptors to respond.
Neurons in successive levels of sensory pathways (second- order neurons, thalamic and cortical neurons-also have receptive fields, although they may be considerably more elaborate than those of the receptors.
TRANSDUCTION
Sensory receptors use ionotropic and metabotropic mechanisms to produce receptor potentials
Sensory receptors transduce some physical stimulus into an electrical signal � a receptor potential � that the nervous system can understand.
Sensory receptors are similar to postsynaptic membranes as their adequate stimuli are analogous to neurotransmitters.
THE DIAMETER OF A NERVE FIBER IS CORRELATED WITH ITS FUNCTION
BIGGER = FASTER
Larger fibers conduct action potentials faster than do smaller fibers.
A? fibers are the largest and most rapidly conducting myelinated fibers.
The slowest conducting fibers of the body are the C fibers
RECEPTORS IN MUSCLES AND JOINTS DETECT MUSCLE STATUS AND LIMB POSITION
MUSCLE SPINDLES
Muscle spindles (Fig. 9-14) are long, thin stretch receptors scattered throughout virtually every striated muscle in the body.
These muscle spindles sense muscle length and proprioception (�one�s own� perception).
They are quite simple in principle, consisting of a few small muscle fibers with a capsule surrounding the middle third of the fibers.
These fibers are called intrafusal muscle fibers (fusus is Latin for �spindle,� so intrafusal means �inside the spindle�), incontrast to the ordinary extrafusal muscle fibers (�outside the spindle�).
The ends of the intrafusal fibers are attached to extrafusal fibers, so whenever the muscle is stretched, the intrafusal fibers are also stretched.
The central region of each intrafusal fiber has few myofilaments and is noncontractile, but it does have one or more sensory endings applied to it.
When the muscle is stretched, the central part of the intrafusal fiber is stretched, mechanically sensitive channels are distorted, the resulting receptor potential spreads to a nearby trigger zone, and a train of impulses ensues at each sensory ending.
GOLGI TENDON ORGANS
Golgi tendon organs are spindle-shaped receptors found at the�junctions between muscles and tendons. They are similar to Ruffini endings in their basic organization, consisting of interwoven collagen bundles surrounded by a thin capsule (Fig. 9-16).
Large sensory fibers enter the capsule and branch into fine processes that are inserted among the collagen bundles. Tension on the capsule along its long axis squeezes these fine processes, and the resulting distortion stimulates them.
If tension is generated in a tendon by making its attached muscle contract, tendon organs are found to be much more�sensitive and can actually respond to the contraction of just a few muscle fibers.
Thus Golgi tendon organs very specifically monitor the tension generated by muscle contraction and come into play whe
n fine adjustments in muscle tension need to be made (e.g., when handling a raw egg).
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Thus the mode of action of Golgi tendon organs is quite different from that of muscle spindles (Fig. 9-17). If a muscle�contracts isometrically, tension is generated across its tendons, and the tendon organs signal this; however, the muscle spindles signal nothing because muscle length has not changed (assuming that the activity of the gamma motor neurons remains unchanged).
In contrast, a relaxed muscle can be stretched easily, and the muscle spindles fire; the tendon organs, however, experience little tension and remain silent. A muscle, by virtue of these two types of receptors, can have its length and tension monitored simultaneously.
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The term posterior column refers to the entire contents of a posterior funiculus, exclusive of its share of the propriospinal tract. The posterior columns consist mainly of ascending collaterals of large myelinated primary afferents carrying impulses from various kinds of mechanoreceptors (although substantial numbers of second-order fibers and unmyelinated fibers are also included). This has traditionally been considered the major pathway by which information from low-threshold cutaneous, joint, and muscle receptors reaches the cerebral cortex.
The cell needs three things to survive.
The health of the neuron, however, plays a huge role in how neurons can produce receptor potentials, the endurance of the neuron and the ability to create plasticity.
Chemoreceptors
Although their morphologies vary widely, all receptors have three general parts:
Sensory receptors use ionotropic and metabotropic mechanisms to produce receptor potentials
Larger fibers conduct action potentials faster than do smaller fibers.
junctions between muscles and tendons. They are similar to Ruffini endings in their basic organization, consisting of interwoven collagen bundles surrounded by a thin capsule (Fig. 9-16).
sensitive and can actually respond to the contraction of just a few muscle fibers.
