Physio C6 - Somatosensory System PDF

PHYSIO C6 - Somatosensory system 1.​ Coding sensory information The digital signal in the NS is the action potential. The action potential is modulated in frequency, time and depends on the properties of the neurons. The nervous system’s physiology can be studied starting from the somatosensor...

PHYSIO C6 - Somatosensory system 1.​ Coding sensory information The digital signal in the NS is the action potential. The action potential is modulated in frequency, time and depends on the properties of the neurons. The nervous system’s physiology can be studied starting from the somatosensory system. Humans must monitor the environment, the variables that can affect the homeostasis There are 2 groups of sensory systems that allow us to explore and to monitor the environment. Despite the diversity of sensation, all sensory systems transduce the 4 basic types of information regading the stimuli: -​ Modality: General class of stimulus, determined by the type of energy trasmitted by the stimulus and the receptors specialized to sense that energy. o​ Receptors + ascending pathways + target brain areas = sensory system. o​ The activity within system gives rise to specific type of sensation (touch, vision, hearing, smell..) o​ The type of energy is coded by modality, coded by the brain and sensory system. If there is contact with an object, the receptors dedicated to this type of energy will discharge but the others don’t. It is interpreted as a mechanical interaction, then the type of interaction needs to be understood (if it is static, dynamic…). -​ Location: Represented by the set of sensory receptors active within a sensory system following a simulus. The topographycal distribution of receptors in sense organs allows to distinguish the modality (types of receptors activated) but also the spatial position of the stimulus and its size. Example: We need to know where we have been in contact. If we keep an object in our hand, our brain needs to know which hand is manipulating the object and which are the features of the object in order to guide our movements in manipulating the object. -​ Intensity: Depends on the response amplitude of each receptor, reflecting the total amount of energy delivered to that receptor. -​ Timing: Defines when th receptor starts and stops reflecting how quickly the energy is received or lost by the receptor. Both the intensity and the time course are coded by the firing pattern of the activated sensory neurons. The higher the intensity, the higher the amplitude of receptor potential and higher the frequency of discharge. The stimulus-intensity-to-frequency coding for sensory receptors can be correlated to the current-to-frequency coding. Skin receptors The time course is based on the adaptation property. There are tonic and phasic receptors. -​ tonic receptors fire through all the stimulation duration -​ phasic receptors are more sensitive to the transient phases and they are coding for the velocity and acceleration of the stimulation, the modulation of the stimulation intensity. There are 4 types of skin receptors: Meissner, Merkel, Pacini, Ruffini. These receptors that are stimulated with the same mechanical stimulation, fire differently. There are 2 families of receptors -​ slow adapting (tonic): Merkel and Ruffini -​ fast adapting (phasic): Meissner and Pacini The skin is equipped with 4 types of receptors, 2 of them are fast adapting and 2 are slow adapting. 2.​ Sensation and perception The senses differ in their mode of reception but share 3 common steps: (1)​ Physical stimulus (2)​ Events transforming the stimulus into nerve impulses (3)​ Response of this signal in the form of a perception or a conscious experience of sensation. Considering the modality and localization: The physical stimulus induces the events of transduction and then the response of the ascending system towards the cortex induces the awareness of stimulation: the sensation. The sensation is conscious awareness of stimulation. There can be sensation of contact, vibration, warm, cold or pain (e.g. if we touch something, the contact is the sensation). Perception is a more complex degree of computation as sensation is the basic. Perception requires a computational analysis. To conclude, the perception is always more complex than the sensation. -​ Sensation is the conscious awareness or experience of a stimulation. -​ Perception is elaboration which is done by the sensory system. Example: if we touch the lips with our hands, the sensation is contact. But how many stimuli are there and are they separated? There are 2 stimuli separated by distance. This is perceptual computation because we need to recognize that we have been in contact and there are 2 stimulations in 2 different positions. So the brain needs to recognize that there are 2 separated stimuli stimulating 2 different fields. And one may have higher intensity with respect to the other. This is a higher level of processing.  3.​ The sensory modality The 5 major sensory modalities a divided in two classes, in respect to their relation to their environment. Modalities without a direct contact with the environment: -​ Vision -​ Hearing -​ Smell -​ Taste Modality with a direct contact is: -​ Somatic: it can be subdivided into o​ Touch o​ Pain o​ Temperature o​ Itch o​ Proprioception o​ Balance The modality accounts for the type of energy and includes vision, hearing, taste, smell and somatic sensation. The special senses explore the world without direct contact. Somatic explores the world with direct contact. They allow us to explore the external world. A.​ Interoception and taste The interoception (the vegetative internal sensory system) which is paired with taste. It is the internal moneitering system made of sensors located in the organs and systems. Taste is the special sense which is connected with the vegetative sensory system which monitors the internal environment not the external. It is a sensory experience related to something that is acquired from the environment. It is subdivided into -​ Salt: amount of Na -​ Bitter: can be poison -​ Sour: amount of hydrogens H -​ Sweet -​ Umami: concentration of glutamate Taste therefore allows the connection between the external world and the interoception. So all of this information is directly related to homeostasis. They are not information that are related with the interactions of the world in terms of exploration but are in terms of nutrition, more related to the internal environment. B.​ Somatic In the somatic there are different modalities. Interactions with the environment can be -​ thermal,  -​ mechanical (touch accounts for mechanical contact), -​ pain (which accounts for potential or actual damage) -​ proprioception (which is the sensory modality that accounts for the stimulation of sensors belonging to joint tendon organs and muscles). In order to be aware of what our muscles, joints or limbs are doing we have to monitor then relate these information with the actual movement with our interactions. C.​ Balance Balance is a special sense but it contributes to integrating with somatic and to the definition of body scheme. D.​ Itching Itching is difficult because it’s not known where it comes from. There are no receptors for itch. Itch and perception of wetness are sensory experiences that arise from the interaction of more than one sensor in the somatic system. Families of receptors For different modalities there are families of receptors. The muscle spindle is a very complex receptor. There are sensory fibres that are enveloping the central portion of the intrafusal fibre. Sensory fibre is a portion of an axon. When the receptor is stretched, the central portion squeezes, and the axon becomes flat. This mechanical deformation opens channels, there is an entrance of the sodium and depolarisation. The receptor of olfactory mucosa is a chemoreceptor. The brain, nasal cavities, olfactory cilia can be seen in the slide. On the cilia there are receptors that bind odorants. The binding with the odorants leads to the opening of channels. If the odorant is not the odorant for that receptor there will be no stimulus. When the odorant is the one that actually fits the receptor, there will be the second messenger pathway that opens the channel. 4.​ RECAP Somatosensory receptors are located all around the body and, based on the region from which the stimulus they perceive comes, they can be divided into: -​ Proprioceptors (somatic sensitivity): the sense of oneself – give perception of posture and movements of one’s body. The presence of sensory receptors allows a more precise and coordinated movement. Receptors in o​ Skeletal muscles o​ Joint capsules o​ Skin o​ -​ Exteroceptors (somatic sensitivity): sense the direct interaction between the body and the external environment. Exteroception principally works through touch (contact, pressure, movement, vibration, thermal information, nociception…). During touch the sensory and motor components are deeply interconnected: in order to have a better  knowledge of the object I have to move the part of my body that touches it; sensory information can make me move a part of my body. Sensing temperature allows the maintenance of homeostasis in our body. -​ Interoceptors (visceral sensitivity): sense the function and state of major organs in the body. The information almost never reaches conscious level (this happens when there is an important disease causing pain), but is necessary to maintain cardiovascular, respiratory, GI and renal system work. o​ Most interoceptors are chemoreceptors that control parameters as pH -​ Special sensitivity, provided by specialized sense organs. Information is carried only by cranial nerves (not found in spinal nerves) and it can be divided in somatic (hearing, balance and vision) and visceral (smell and taste) components. a.​ Classification of sensory fibers Sensory modalities and sub-modalities can be also classified by the form of the energy they transduce. However, each receptor, independently from the energy working on it, is an organ that has to transduce a modality into an electrochemical signal, according to its 4 characteristics (modality, location, intensity, timing). The different modalities of somatic sensation are mediated by peripheral nerve fibers that are classified based on different criteria: 1.​ Diameter: larger diameter means less internal resistance 2.​ Conduction velocity Based on diameter, there is an anatomical subdivision of the sensory fibers Functionally important in muscles: -​ Group I fibers innervate muscle spindle receptors and Golgi tendon organs. -​ Group II innervate receptors in joint capsule -​ Group III are the smallest afferents from muscles -​ Group IV signal pain and therefore disorders In the skin we find: -​ Group I and II fibres (Aα+Aβ): mechanoreceptors that respond to touch -​ Group III and IV fibres (Aδ and C): mediate thermal and noxious stimuli Another method for classification of peripheral nerves is based on electrical stimulation: there is the measurement of the conduction velocity by using pairs of stimulating and measuring electrodes placed on the skin above the peripheral nerve. The stimulation causes APs; electrical stimuli of increasing strength evoke action potentials in the largest axons first, as they have the lowest resistance. ​ The earliest signal recorded comes from fibers with conduction velocities >90 m/s: the Aα wave (can be found in group I and in motor neurons for skeletal muscles). ​ Aβ waves correspond to group II ​ Aγ wave are an intermediate velocity in between β and δ and innervate muscle spindles. ​ Aδ waves come after, with smaller fibres (III); the recruitments of these fibres involve the pain feeling ​ C waves, unmyelinated fibres evoke burning pain (IV) The different fibers are targeted by different neurodegenerative disorders so the loss of one or the other wave is used in order to understand what is going on. Prompt signaling from peripheral nerve is needed in order to avoid a conduction delay: -​ A prompt motor control would be impaired by the delay -​ Conduction delay would cause a second problem: among different afferent fibres there are different velocities. If neurons fire together and they have different conductance, the stimuli will reach the target in different moments which are consistent with the mean conduction delay and variation of conduction velocities. Even though there is difference of speed in the various fibers, the synchrony is almost completely maintained as the difference in speeds is not that relevant.  b.​ Somatic sensitivity Morphological and molecular specialization of nerve terminals allow different receptors to sense specific forms of energy. The different forms travel in distinct pathways. All first order sensory neurons are dorsal root ganglion neurons (except those for the face). 1)​ Epicritic (fine touch) -​ Detect gentle contact of the skin and localize position touched (topognosis) -​ Discern vibration in frequency and amplitude -​ Touch spatial details, texture of surfaces and two-point discrimination -​ Recognize shape of objects (stereognosis) -​ Mechanoreceptors – encapsulated terminals, large diameter, low threshold, myelinated axons that conduct action potentials rapidly. 2)​ Protopathic (crude touch): -​ somatic sensations cannot be localized in a specific place -​ Different fibers responsible for the different types of sensation: temperature, pain, itch and indiscriminative touch. -​ Thermal receptors and nociceptors – bare nerve endings, small-diameter axons, either thin and myelinated or unmyelinated that conduct impulses more slowly. The receptor at the end of the neuron determines the type of stimulus received: Nonneural capsule: present in receptors for touch and proprioception faster signaling. They sense a physical deformation of the tissue in which they reside. -​ The stimulus is transduced thanks to the cation channels on the neurons’ PM. Mechanical stimuli deform the receptor-channels (for Ca2+ and Na+), opening it. Removing the stress, the receptor is free to close. Gates can either open directly (it has been hypothesized that the stresses on the lipids of the PM open these gates) or be linked to the surrounding tissue cell membranes through structural proteins; the force is then sent to the receptor that reacts consequently. -​ Also, some mechanoreceptors work with second messengers; in this case the channel and the proteins that perceives the stimulus are not the same because they are connected through a signalling cascade (slower path both to activate and deactivate the channels)-but allows amplification of the signal. In mammals, proteins involved in the transduction of signals in proprioception have not been identified. Unsheathed nerve endings with multiple branches: receptors for nociception, thermoreception and chemoreception As the receptor is activated, the neuronal terminal is depolarized: if depolarized enough, this causes the AP. Also, the end organ of the sensory neuron is critical in order to get various stimuli: different receptors respond selectively e.g. to pressure or to movement; may detect the force in one direction and not another. The end organ can also modulate or amplify the sensitivity. 5.​ How does the brain distinguish between the different energies – the labelled line code Receptors are specialized to transduce ≠ types of energy: there is a receptor specificity to a certain energy and an adequate stimulus arises from that energy. The stimulus is under the form of an action potential that travesl on the axon of the receptor. The axon is the specific modality for the line of communication. The brain makes a ≠ between the ≠ types of modalities by the fact that each class of receptors makes connections with distinctive structures in the CNS. The modality is therefore represented by the ensemble of the neurons connected to a specific class of receptors that all dorm a sensory system such as the somatosensory, visual, auditory, vestibular , olfactory and gustatory systems. For example, to distinguish between the information coming from a thermal receptor from the one coming from a mechanoreceptor: All mechanoreceptors will converge in a specific ascending pathway that will be separated from the others: the distinction between the different type of stimuli is based on space. the visual system is sepreated from the olfactory, etc The information coming from the different receptors will travel in a peculiar position in the spinal cord and in the thalamus in order to reach the cortex. The cortex at the end will receive information from different systems coming from different pathways and will automatically translate into an experience. This process is called labelled line code: the receptors of the same family will not mix up with the others. Some examples of ascending pathways are the dorsal column, the anterolateral system, the spinocerebellar: these are separated all the way towards the final target. Lesion -​ A lesion at the level of the skin will lead to the loss of every sensation because the receptors present in the skin are damaged. -​ On the other hand, there will be a different outcome if the lesion is in the spinal cord where the fibres travel separated: the anterolateral system decussates immediately while the dorsal column goes up ipsilaterally and decussates at the level of gracile and cuneate. If there is a hemi section of the spinal cord one modality of the same side will be lost below the lesion and the other modality will be lost contralaterally. The somatosensory system contains receptors located in the skin, muscles, tendons, joints and all go up towards the supraspinal centres, either cerebellum or cortex, in different tracts correlated to the different modalities and do not mix up. a.​ Receptor specificity The graph below shows the so called “tuning curve”: it indicates that the receptor is sensitive to one type of energy (sound in the graph), but the activation of the receptor needs more or less intensity of the energy depending on its proper sensitivity. The receptor when stimulated with sounds at different frequencies reacts differently. Sounds at 2 kHz are the ones that better excite the receptor, whereas if you move to higher or lower frequencies the receptor is still activated but needs more intensity of stimulation. b.​ Spatial distribution - location The second main parameter is the spatial distribution: the functional unit is the receptive field indicated by the black lines. Each receptor takes over an area of the skin which means that if that area is stimulated, the receptors that are monitoring that area will be excited. RF have two charcateristics: -​ receptive fields are partially overlapped when a refined sensory monitoring is needed. -​ The peripheral portion can overlap but the central portion is clearly separated. The receptive field can be bigger or smaller depending on the receptor. For example, if a pressure is applied in the red region in the image, this will excite 3 receptive fields as can be seen. But the amount of activation of the 3 is different: the one which is completely stimulated will react with a higher intensity with respect to the others. c.​ Intensity The intensity determined by the stimulus is encoded by the frequency of action potentials. d.​ Duration of stimuli The duration of the stimulus is determined by the adaptation rates: -​ When a fast-adapting receptor, the Pacinian corpuscle, is stimulated with a stimulus (onset, steady state, offset) that is applied according to a sinusoidal modulation, an action potential corresponding to each sinusoidal ascending or descending phase. A sinusoidal pressure leads to a sensation of vibration: by looking at the action potential it is possible to see a constant frequency that the brain receives. The brain recognizes that this is the labelled line of the fast-adapting receptor so when this type of receptor fires, with a high frequency of discharge, means that the stimulus is changing and if it’s regular it means that there is a regular change, a sinusoid, so it is interpreted as a vibration. -​ Slow adapting receptor like Ruffini, it means that there is a stable pressure applied to the skin and the brain can estimate which is the intensity.  The interpretation made by the brain is refined: by applying a stable pressure or a variable pressure the brain perceives it as pressure, but the brain can also tell, based on the properties of the receptors that are firing, which information is running in which tract and in which segment. 6.​ Convergence The functional and anatomical organisation of the sensory processing networks is hierarchical: sensory systems process information through relay nuclei. For example, in the image below, there is a patch of skin with three different receptors. -​ If a stimuli is in the center of a RF, the discharge will be high. Parralelly, the stimuli does not have to be of great intensity to induce a response. -​ If the stimulation is at the periphery of the RF, it has to be of very high intentisty to induce a response. If there is no stimulation of the tip of the axon, no action potential will be initiated. Therefore, the intensity needed to activate the receptor depends on the position where the stimulus is applied compared to the receptive field. The stimulus is applied to a specific part of the patch of skin and, as has been discussed before, the receptor right under this skin area will be the more excited. The receptive fields of the receptors near this are excited less than the one in the middle because of the overlapping of the receptive fields. There will be a higher frequency of discharge in the middle and lower at the periphery. This phenomena is called the convergence: the axon of a receptor, whose centre of RF is on the stimuli area, will project to a 2nd order neuron associated to it, but also to the 2nd order neurons of the neighbouring RF who overlap partially the main FR. This refinement allows a spreading and a widening of the stimuli of the 2nd order neurons compared to the initial stimuli on the skin. The excitation spreads. 7.​ Divergence If the same situation happens in the skin where the receptors are organized as in the picture below, the difference is in the 2nd order neuron that produces an inhibitory loop on the neighbours: the interneurons that are fed by the 2nd order neurons will inhibit the neighbours so the receptor that is the most excited will be stronger in inhibiting the others. This is a case of divergence. The picture B2 shows the spatial distribution of the excitation: the neighbour relay nuclei are inhibited, hyperpolarized. The inhibition of the neighbours leads to a stimulus that is sharply conveyed, allowing a more precise stimuli to be transmitted by the 2nd order neurons compared to the initial stimuli. in this case (B1, B2) there is a high precision and high spatial resolution. In case A1, A2 the precision is lost. Divergence is very present in the pathways of the brain: initially, an afferent ascending fiber of a 2nd order neurons is able to stimulate or inhibit 3rd order neurons, depending on the stimuli by feedfowarding. The 3rd order neurons are able to modulate in between themselves by feedback loops. Divergence also occurs when descending fibers are also modulating the expression of 3rd order neurons in a distal way. These inhibitory circuits present inside relay nuclei are essential for the integration and refinement of stimuli. The divergence and convergence of stimuli causes the ascending pathway of the somatosensory cortex to not always be neutral: the information can be modulated and therefore changed depeding on the organisation of the pathway. If the pathway is organised like a B1, there will be a faithful spatial transmission of the stimuli because the intensity of the stimuli is encoded by the number of receptive fields in addition to the frequency of discharge a one receptor (not only that). d. If a high pressure is applied, also the neighbours will be stimulated but less involved. In A1 and A2 as seen before, the transmission is not precise because it is spread. In B1 and B2, the neighbours do not affect the precision of the stimulation: it is precise and will be translated as precise. The way the cortex is reached will therefore depend on the organization of the network of fibres. Relay nuclei are places where the information is modified.  I.​ The sense of touch The somatosensory system has two major components: the subsystem that detects the mechanism stimuli and the subsystem that detects of the painful stimuli and the temperature. The somatic sensitivity is organized in 4 modalities: -​ Discriminative touch: allows to distinguish and recognize the size, the shape, the texture of objects and their movement across the skin and vice versa. o​ It is different to crude touch which is referred to mechanoreceptors that travel through the anterolateral system conveyed with thermal and the pain receptors information; -​ Proprioception: to sense the static position and movement of the limbs and body; -​ Nociception: signalling of tissue damage or chemical irritation. Pain is not a type of energy, and all energy are potentially painful depending on their ability to make damage. Pain is a sensation that arises from the nociceptive system where there are nociceptors that are able to detect information that can be potentially or actually damaging; -​ Temperature sense: warmth and cold. The somatic sensitivity arises mainly from the neck below, from neurons that have the body in the dorsal root ganglia, one branch towards the periphery and one entering the system through the dorsal roots. The image below shows a Pacinian corpuscle and the axon divides into an ascending branch and into a branch that stays in the spinal cord. Therefore, it is important to underline that the receptors are also working in the spinal cord. Somatic sensitivity can be divided into epicritic and protopatic (see def higher) Classification of fibers A classification of fibres based on diameter, conduction velocity, different receptors , motor fibres and muscular receptors. -​ Refine touch, which uses the 4 types of skin mechanoreceptors, is transmitted exclusively through Aβ fibres, 60 m/s, from average 10 micrometres diameter. Other types of cutaneous receptors are the nociceptors and thermal receptors: -​ fibres for hot temperature are Aδ -​ fibers for cold temperature they are C fibres -​ nociceptors are A δ or C. Considering proprioception, there are the Golgi tendon organs and the muscle spindles, these are the fastest fibres. Proprioceptors are the fastest because they have big, myelinated axons. Receptors coming from muscles and tendons convey information fast and this makes sense: the velocity used by the skeleton motor system must be fast in order to constantly monitor what is going on. Nociceptors, on the other side, are not fast. 1.​ Mechanoceptors There are four major types in the glabrous skin, and they are classified based on the localization, functional properties and size and structure of the receptive field. The two superficial receptors are the Merkel and Meissner, the deep ones Pacini and Ruffini. The velocity ranges from 35 to 70 m/s, they are Aβ fibres, and in the hairy skin there is also the receptor for the hair fibres. All the 4 receptors have a common feature, which is that they all have the ending portion of the axon which is specialized as receptor. Some are equipped with accessorised structures. Mechanoreceptors, which comprise both exteroceptors and proprioceptors, are activated following physical deformation due to touch, pressure, stretch, or vibration of the skin, mus cles, tendons, ligaments, and joint capsules, in which they reside. A mechanoreceptor may be classified as nonencapsulated or encapsulated depending on whether a structural device encloses its peripheral nerve ending component. a.​ Meissner corpuscule (superficial layer of skin) Meissner’s corpuscles are present in the dermal papillae of glabrous skin of the lips, forearm, palm, and sole, as well as in the connective tissue papillae of the tongue. These corpuscles consist of the peripheral terminals of Aβ fibers, which are encapsulated by a peanut-shaped structural device consisting of a stack of concentric Schwann cells surrounded by a connective tissue capsule. They are rapidly adapting and are sensitive to two-point tactile (fine) discrimination, and are thus of great importance to the visually impaired by permitting them to be able to read Braille.  b.​ Merkel disks (superficial layer of skin) Merkel disks consist of disc-shaped, peripheral nerve endings of large-diameter, myelinated, Aβ fibers. Each disc-shaped terminal is associated with a specialized epithelial cell, the Merkel cell, located in the stratum basale of the epidermis. These receptors are present mostly in glabrous (hairless), usually in clusters ate the center of the papillary ridge. Merkel’s discs respond to discriminative touch stimuli that facilitate the dis tinguishing of texture, shape, and edges of objects. They are slow-adapting and sustained. c.​ Pacinian corpuscle (deep subcutaneous tissue) Pacinian corpuscles are the largest of the mechanoreceptors, are rapidly adapting and resemble an onion in cross-section. Each Pacinian corpuscle consists of Aβ-fiber terminals encapsulated by layers of modified fibroblasts that are enclosed in a connective tissue capsule. Pacinian corpuscles are located in the dermis, hypodermis, interosseous membranes, ligaments, external genitalia, joint capsules, and peritoneum, as well as in the pancreas. They are more rapidly adapting than Meissner’s corpuscles and have a lower reponse threshold. They are believed to respond to pressure and vibratory stimuli, in cluding tickling sensations, as they respond to rapid indentations of the skin. The flexible attachments to the skin allows the receptor to sense the vibration (even far away) d.​ Ruffini ending (deep subcutaneous tissue) Ruffini’s end organs (corpuscles of Ruffini) are located in joint capsules, the dermis, and the underlying hypo dermis of hairy skin. The unmyelinated peripheral terminals of Aβ myelinated fibers are slowly adapting. They intertwine around the core of collagen fibers, which is surrounded by a lamellated cellular capsule. Ruffini’s end organs respond to stretching of the collagen bundles in the skin or joint capsules as may occur during movement of a limb, relaying sensory input for kinesthesia. They may provide proprioceptive in formation that aids in maintaining balance and posture. They therefore sense the stretch of the skin or bending if the fingernails because they are compressed and contribute to the perception of grasped objects. 2.​ Functional properties of mechanoceptors. Considering fast adapting and slow adapting receptors: -​ Fast adapting I (FAI): Meissner -​ Slow adapting I (SAI): Merkel -​ Fast adapting II (FAII): Pacini -​ Slow adapting II (SAII): Ruffini All 4 receptors are specializations of the distal part of the axon and each one of them is equipped with different sensory structures. It is important to note that the receptive field is related to the position of the receptor on the skin. The superficial-most receptors have a small receptive field when compared with the receptors located deeper in the skin. All receptors are distributed in different densities in the skin therefore they are not homogenously distributed since there are areas where a certain receptor is highly concentrated, depending on the part of the body analysed. The smaller the receptive field higher the number of receptors. The superficial receptors have a small receptive field, and the highest amount of these receptors are in the tip of the fingers, tongue and lips. By looking at the receptive fields in the image , it is possible to see concentric lines that are the representation of the intensity needed to activate the receptors. The black dots in the receptive fields are the branching of the axons. In the centre of the receptive field, the stimulus to trigger the action potential is way lower than the stimulus needed to trigger an action potential when is produced outside of the centre of the receptive field (higher sensitivity = Centre, Low sensitivity = towards the periphery of the receptive field). The superficial skin receptors have a sharp increase and decrease in excitability based on the position of the stimulus in relation to the centre of the receptor whereas the deep subcutaneous receptors have a more gradual increase and decrease in excitability based on the position of the stimulus in relation to the centre of the receptor. The tip of the finger, face and the tip of the tongue are the 3 districts of the body where there is the highest density of receptors. These 3 are the most used segments of the body for the finest movements: they have the highest sensitive ability. Looking at Pacini and Ruffini, the receptive fields are bigger (can be as big as a finger for example). The deep receptors are also involved in the transmission of information regarding the displacement of the superficial and deep layer of the skin (for example, the movement of the deep layer of the skin and joint) and so, they contribute to the monitoring of the position of the joint (proprioception). There are critical positions where the deep receptors become proprioceptors. These are two graphs representing the frequency of discharge of Meissner (on the left) with increasing pressure velocity. This is a velocity to frequency coding since there is a direct correlation between the frequency of discharge of the receptor and the increasing pressure velocity. If the frequency of discharge is increased in a slow adapting receptor like a Merkel the result will be an intensity to frequency coding: the higher the intensity of the indentation the higher the frequency of discharge. 3.​ Thermoception The warm fibres (1.2 +- 0.5 m/sec) are slower than cold fibres (14.5 +- 4.9 m/sec). -​ Cold receptors are most responsive to temperatures at or slightly above 20°C, -​ warm receptors show a peak response at 40°C and in temperatures higher than 40°C, the frequency of discharge decreases (the same occurs for cold receptors when the temperature is lower than 20°C). By increasing the temperature on the skin there is an increase in the frequency of discharge. The thermo-receptors have a bell-shaped curve of frequency of discharge in respect to the temperature analysed which can be a problem because for example, the cold receptors have the same frequency of discharge for temperatures around 20°C and for temperatures around 30°C. Focusing for example on the warm receptors, the same frequency is for 38°C and 48°C. The same happens for the receptor for cold, where 4 Hz corresponds to 25°C and 35°C. This problem is circumvented by the brain because the brain always needs confirmation from other receptors to give an appropriate response (in the case of cold receptors, the warm receptors and nociceptors, which fire in temperatures above 45°C and below 20°C). If it is winter and the skin is cold, entering in a room an putting the hands on a heater the person does not instantly feel warm but less cold: thermal reception depends on the starting temperature. 4.​ Nociception/pain The pain is an unpleasant sensory or emotional experience associated with actual or potential tissue damage or described in terms of such damage. Specific nociceptors are there to ring the bell when something is potentially dangerous. iT is important for survival, protect from damage. A congenital and acquired insensitivity (diabetic neuropathy, neurosyphilis) to pain can lead to permanent damage. The perception of pain is a product of the brain abstraction and elaboration of sensory inputs. The perception of pain varies with individuals and circumstances. The activation of nociceptors does not necessarily lead to the experience of pain (asymbiolia under morphine). The pain can be perceived w/o the activation of nociceptors (phantom limb pain, thalamic pain syndrome). The pain reflex can be stopped if not appropriate (step on nail near precipice, burn hands while holding a baby). It can be stopped of not need for survival. It is possible to classify the pain into: -​ Physiological (nociceptive pain) – pain sensation arriving from the involvement of the nociceptive system, through a direct stimulation of nociceptors. o​ somatic (bones, ligaments) – there is a cortex for its localisation  o​ visceral (internal organs) – no precise region on the cortex (no somatotopism), hence difficult to detect. Some organs are without nociceptors: livers, brain (in the meninges yes). Somatic ones are cutaneous and deep receptors. -​ Originates from bones, ligaments, skin, muscle etc -​ High density of nociceptors -​ Pain is easy to localise -​ The feeling of the pain is burning and sharp (cutaneous); dull, aching and cramping (deep). Visceral ones originate from internal organs or hollow structures: -​ Low density of nociceptors -​ Pain is hard to localise -​ The feeling of the pain is diffused, deep cramping, stabbing, sometimes nausea. -​ Neuropathic (intractable pain) – result from injury to the peripheral or central nervous system that causes permanent changes in circuit sensitivity and CNS connections. Th pain may be referred to a specific region of the body due to an injury in different portions of the NS. Neuropathic pain can be due to different mechanisms. The pain travels through pain fibers, which are special sensory neurons with several nociceptors. The nociceptors are affected to both temperature, chemical and mechanical stimuli in the tissue. In the dorsal horn of the spinal cord, fibers coming from nociceptors transmit the “pain signal” to neurons, which then carry it to the brain. The transmitting of the signal is controlled by spinal and supraspinal gating. a.​ Functional propreties of nociceptors There are 3 different families of nociceptors: -​ specific (Aδ fibres, 5-30m/s): -​ polymodal (C fibres, 3m/s) -​ silent (Aδ –C fibre) Specific They carry information though Aδ fibres, the fastest ones – 5-30 m/s. Specific receptors are thermal or mechanical. They have the same behaviour as mechanic and thermic receptors in the skin – slow and fast adapting, intensity to frequency coding. They differ from normal receptors by having a different intensity of stimulation, the threshold to have their activation is higher than in thermal and mechanical receptors in touch sensing. They inform about a potential damage, telling the brain that if this stimulation is not removed a damage will be provoked (‘guys if we go on like that there will be a damage’). Polymodal They carry information through C fibres, which are very slow – 1 m/s. They can be stimulated with multiple kind of energy, and they always discharge for the different energies. Why do we feel fresh with menthol candies – menthol is a molecule reacting with cold receptors in the mucosa. The same goes for pepper and chilly about feeling warm. Polymodal are activated only when there is an actual damage. Polymodal simply inform about the presence of a damage. Polymodal receptors are not equipped with all of the receptive functions for the different types of energy, they are actually chemoreceptors or chemothermal receptors (if also thermal energy can stimulate these receptors) that are responsive for mediators of inflammation – bradykinin and cytokines, released in the site of inflammation. Polymodal receptors can be activated by endogenous or exogenous receptors and the stimuli can be mechanical, thermal or chemical. They never adapt; therefore, they are sensitised, the opposite of adaptation. Sensitisation makes a receptor more performant – reduce threshold of activation, current to frequency coding shifted to lower values, spontaneous discharge in some cases and persistence of the discharge even after the end of the stimulus, everything is overexcited. It undergoes sensitisation but it does NOT require it in order to fire. I.e. for a lesion on the skin. The response is in presence of the damage, due to the stimulation of the inflammatory response. Silent Silent have a very high threshold. If they are sensitised, they become active, once they are they discharge very strongly. It undergoes sensitisation and it DOES need it in order to fire. The distribution of the receptive field is not homogenous. The red line for the thermal nociceptor is the frequency of discharge. After the threshold there is an expected frequency of discharge, and here is an intensity to frequency coding. The purple line tells about the pain sensation – intensity of sensation of pain parallels perfectly to the receptor activity. b.​ Threshold of nociceptors In the graph , from 45/45°C there is a significant discharge and here there is the thermal to frequency coding. The purple line talks about the pain sensation: this one parallels the behaviour of the receptor. This is different from that of the mechanoreceptors. The nociceptor is non-reactive for a low-intensity non-dangerous stimulus, whereas there is the activation hen the intensity of the stimulus may or is causing a danger for the organism, here the receptor fires – both for the thermal and the mechanic nociceptors, one with the temperature as intensity and the other with pressure. The relationship between the discharge and the intensity of the stimulus display a linear correlation. Therefore, the nociceptors will be activated with a very high intensity of stimulation for the specific nociceptors or with a very low intensity for the polymodal (inflammation) or for the silent ones (once activated fire with very low intensity of stimulation). c.​ Fibers Nociceptors carry their signals either with Aδ or C fibres. They have a different conduction velocity, therefore different experiences happen when one of the 2 or both are activated. When there is a noxious stimulation there is the: -​ First pain – acute and very sharp, immediate. o​ Fibres conducting the stimulus are Aδ. -​ Second pain – aftereffect, second discomfort related to the area where the noxious stimulation has been provided. o​ Fibres conducting the stimulus are C fibres. The 2 pains are felt in 2 different moments due to the different conducting velocity of the 2 fibres.  5.​ Sensitization When the pain-pathway becomes oversensitive it is called sensitization. If the nociceptors continue to register signals, they will become very sensitive and begin to react to even weak stimuli. This can lead to chronic pain. It is a consequence of inflammation – the receptors respond to chemicals of the inflammation and afterwards become very active. This can be thought as a protective mechanism, hence informing about an inflammation. As a neuron is sensitised, the neuron can also undergo spontaneous response. Sensitisation can happen in 2 levels: -​ Periphery – where the receptor is presence, this is the one changing the properties.This is almost always reversible and can be removed. -​ Central levels – at the spinal cord where the second order neuron (projection) undergoes sensitisation. After carrying the signal to supraxial levels or the thalamus. o​ This can be long lasting and can lead to chronic pain. This is an example of neuropathic pain. o​ This is important to be avoided during surgery for instance, by the administration of drugs to inactivate this mechanism. a.​ Axonal reflex The sensitization results in the release of various chemicals by damages cells and tissues (bradykinin, prostaglandins, leukotrienes, …). These chemicals will alter the type and number of membrane receptors on free nerve endings, lowering the threshold for nociceptive stimuli. The axonal reflex corresponds to the situation in which the depolarized nociceptive sensory ending release substance P, thus contributing to the spread of oedema by producing vasodilation, an increase of vascular permeability, a plasma tranvasation and the spread of hyperalgesia by leading to the release of histamine from mast cells. Therefore, the nociceptors both tells the brain that there is a damage and at the same time it stimulates inflammation, which is the protective mechanism. By enhancing inflammation, the receptor increases the possibility to be sensitised, this is a positive feedback. This is a protective mechanisms. Aspirin and NSAID block the formation of prostaglandins by inhibiting the enzyme FOX. Local anaesthetics preferentially block C fiber conduction, cold decreases the firing of C fibers, ischemia blocks the large myelinated fibers.  b.​ Sensitisation consequences perceived The experiential consequence of sensitisation is called hyperalgesia – the increased sensitivity to an already painful stimulus. Once the receptors is sensitised the intensity of the pain felt will be higher. Allodynia – sensation of pain for a stimulation that is not painful. For example – touch a patch of burned skin, it hurts, but the touch per se is not painful, the pain is felt because the area has been sensitised. c.​ Sensitisation consequences on the receptor Main consequences – the receptors is made hyperactive once sensitisation has occurred: -​ Spontaneous activation of the receptors. -​ Decreased threshold for the activation. -​ Persisting response. -​ Increased response. An example of the possible interaction of the receptor by means of the release of mediators of inflammation: II.​ Somatic sensitivity – proprioception It is a modality referring to mechanical energy. These are crucial information but not immediately made available at the conscious level – would consume too many resources of concentration. The brain processes these sensory inputs to create perceptual representations of limb movements. There is no detailed sensation but there will be a complex final image of the body at the conscious experience (f.e. about the limbs – just need to know where they are, if they are moving and the relation between them). At the unconscious level, for the motor system, more detailed information is provided in order to provide the correct response – contraction of the correct muscle. This is called secrete sense: continuous but unconscious sensory flow from the movable parts of our body (muscles, tendons, joints), by which their position and tone and motion are continually monitored and adjusted, but in a way which is hidden from us because it is automatic and unconscious. Thanks to proprioceptors there is information about: Position sense – conscious awareness of the relative positions of our body parts in space. Kinaesthesia – sense of: -​ Movement -​ Speed of movement -​ Direction of movement -​ Heaviness (sense of effort) Proprioception – signals contributing to conscious and subconscious mechanisms of motor control. 1.​ Location of receptors The receptors that provide signals appropriate for kinaesthesia and position sense are in the joints (joint receptors), muscles (muscle spindle receptors), tendons (Golgi tendon receptors) and in the deep layers of the skin (Pacini and Meissner) In the deep skin are Pacini and Meissner that can sometimes behave as proprioceptors, depending on where they are located in the body. 2.​ Joint receptors Joint receptors are located in the joint. They are free ending fibres entering into the joint. They can be either fast adapting or slow adapting. They resemble in some cases Pacinian and Meissner in the deep layers of the skin. Have similar features to receptors in the skin in general.  a.​ Intensity of stimulation In the case of joints, the intensity stimulation is the angular displacement – how much in term of angular displacement the joint has moved. b.​ Fast and slow adapting Fast adapting – code for the velocity (speed of displacement) and the final angle. It codes for the transient state. This fires with higher frequency of discharge when the velocity is higher. This is true for both directions of movement. Slow adapting – code for the position, the frequency of discharge codes for the amount of extension/flexion, hence it codes for the total amount of displacement. For the slow adapting there are receptors coding for the amount of extension and other coding for amount of flexion. The ones for extension have a higher frequency of discharge depending on the degree of extension – more extension, more discharge. c.​ How do the receptors work How is it possible to distinguish the movement of extension and flexion, and what about the maximal angle? The mount of displacement must be referred to the maximal angle – with respect to the total amount how is the joint positioned? This can be known because of the presence of different receptors in the joint. Each family is responsible for a different specific range of angle. For the specific range there will further be 2 groups – one increasing the frequency of discharge when going towards one region of the range and the other the opposite, therefore one towards extension of the range and the other towards the flexion. It is possible to cover the absolute angle by means of several families, and thanks to the 2 groups discharging when there is more extension or flexion within the range, the direction of the movement can also be defined. The absolute angle is computed at the level of the thalamus – it integrates the signal coming from the different families and is capable of telling how much the joint is being moved from the initial position of the joint. The brain monitors every receptor, based on the frequency of discharge of the different families, it will understand if there is a flexion or an extension and in which domain we are moving. For example: We have 2 families – one from 10-20 degrees (family A) and one from 20-40 degrees (family B). Within the 2 families there are 2 subfamilies, one discharging with higher frequency as level of extension increases and one discharging with higher frequency when flexion increases. If there is a flexion going from 12 to 18: -​ Family B is not discharging because it is not in its domain. -​ Family A is discharging because in their domain. The ones that are responsible for flexion are discharging with a high frequency, the others not. The brain so understand that there is a flexion in the domain of 10 to 20 degrees. The ranges and the signals are much more complex actually, there are overlaps and depending on the frequency of discharge of the various stimuli an interpretation can occur by means of the thalamus. The brain therefore always looks for a confirmation – the one of flexion is firing, then it is flexion, but is it actually? In order to answer the brain checks that the ones of extension are not firing. The same goes for the ranges in which the joint is moving. 3.​ Muscle spindles a.​ Structure and function Skeletal muscle consists of extrafusal and intrafusal fibers -​ Extrafusal fibers are ordinary skeletal muscle cells constituting the majority of gross muscle, and their stimulation results in muscle contraction. -​ Muscle spindles, composed of small bundles of encapsulated intrafusal fibers, are dispersed throughout the gross muscle. These are dynamic stretch receptors that continuously check for changes in muscle length. Each muscle spindle is composed of 2–12 intrafusal fibers enclosed in a slender capsule, which in turn is surrounded by an outer fusiform connective tissue capsule whose tapered ends are attached to the connective tissue sheath surround ing the extrafusal muscle fibers. They are anchored to the fibres but at the same time separated, as they are autonomous structures. Structure There are two types of intrafusal fibers based on their morphological characteristics: -​ nuclear bag fibers -​ nuclear chain fibers. Both nuclear bag and nuclear chain fibers pos sess a central, noncontractile region housing multiple nuclei, and a skeletal muscle (myofibril-containing) contractile portion at each end of the central region. The nuclear bag fibers are larger, and their multiple nuclei are clustered in the “bag like” dilated central region of the fiber : the contractile portion is polar, givibg a central swollen portion. There are usually 2 bag fibers in a muscle spindle. The nuclear chain fibers are smaller and consist of multiple nuclei arranged sequentially, as in a “chain” of pearls, in the central region of the fiber. Their nuclei is in the center but they are tubular and arranged in line. Sensory innervation Each intrafusal fiber of a muscle spindle receives sensory innervation via the peripheral processes of pseudounipolar sensory neurons whose cell bodies are housed in dorsal root ganglia, or in the sensory ganglia of the cranial nerves (and in the case of the trigeminal nerve, within the trigemi nal ganglion and its mesencephalic nucleus). Since the large- diameter Aα fibers spiral around the noncontractile region of the intrafusal fibers, they are known as annulospiral or primary endings. These endings become activated at the be ginning of muscle stretch or tension. In addition to the annulospiral endings, the intrafusal fibers, mainly the nuclear chain fibers, also receive smaller diameter, Aβ peripheral processes of pseudounipolar neurons. These nerve fibers that terminate on both sides of the annulospiral ending are referred to as flower spray or secondary endings and are activated during the time that the stretch is in progress. Motor innervation In addition to the sensory innervation, intrafusal fibers also receive motor innervation via γ motoneurons (fusimotor neurons) that innervate the contractile portions of the intrafusal fibers, causing them to undergo contraction. Since the intrafusal fibers are oriented parallel to the longitudinal axis of the extrafusal fibers, when a muscle is stretched, the central, noncontractile region of the intrafusal fibers is also stretched, distorting and stimulating the sensory nerve endings coiled around them, causing the nerve endings to fire. However, when the muscle contracts, tension on the central noncontractile region of the intrafusal fibers decreases (which reduces the rate of firing of the sensory nerve endings coiled around it). During voluntary muscle activity simultaneous stimulation of the extrafusal fibers by the α motoneurons, and the contractile portions of the intrafusal fibers by the γ motoneurons, serves to modulate the sensitivity of the intrafusal fibers. That is, the γ motoneurons cause corresponding contraction of the contractile portions of the intrafusal fibers, which stretch the central noncontractile region of the intrafusal fibers. Thus, the sensitivity of the intrafusal fibers is constantly maintained by continuously readapting to the most current status of muscle length. In this fashion the muscle spindles can detect a change in muscle length irrespective of muscle length at the onset of muscle activity. It should be noted that even though they contract, the intrafusal fibers, due to their small number and size, do not contribute to any significant extent to the overall contrac tion of a gross muscle. Both fibres are sensitive to the stretch of the muscle. 1A fibres are both fast and slow adapting fibres: -​ At the transient phase there is a high frequency of discharge. -​ The frequency of discharge is then increased, this is maintained through all the duration of the elongation. -​ When the stimulus is removed, the discharge stops and there is the going back to a background potential. 1A fibres have a background discharge when the muscle is at rest, hence the length is the resting length of the muscle. Then there is a stretch, 1A fibres in this case code for the velocity and the acceleration of the stretch, but also for the final amount. It is the phasic and tonic receptor together. Given its behaviour, this is a perfect receptor – it codes for the velocity, the acceleration, the final amount and the end of the stimulation by reducing the background discharge. Afferent innervation This is possible thanks to the intrafusal fibre conferring the properties to the 1A fibres. -​ 1A fibre innervates all of the intrafusal, the 2 bags and the chain. One of the 2 bags is the dynamic one and the other is the static – they have different viscosities in the fibre. o​ The mechanical reaction of the static bag is the one that will excite the branch of the axon connected to it, and this branch is responsible for the fast-adapting properties. o​ The mechanical reaction of the dynamic bag is the one that will excite the branch of the axon connected to it, and this branch is responsible for the slow-adapting properties. The displacement of the dynamic bag is different with respect to the others and will be proportional to the acceleration and the velocity. It is not the membrane of the axon, it is the fibres connected to the branch of the axon that confers the property. Type 2 fibres code for the final intensity, not for the velocity. Type 2 are only slow adapting. The information conferred from the 2 type fibres will be integrated and confirmed to those of the 1A fibres. Efferent innervation The polar portion of the muscle spindle (contractile portion) is innervated by γ motor neurons – they are able to contract the polar portion. Muscle spindle at rest – 1A fibre is discharging with a background discharge – the brain detects it as the length of the muscle is the one at rest, there is no variation in length. Muscle is at rest, the spindle is ready to be stretched – if the muscle is stretched the spindle would be capable to detect it. The spindle works perfectly when the muscle is at rest. Muscle is contracted, it shortens, and the spindle becomes floppy – no further stretches are able to be detected. The starting point would need to be regained before in order to reach the initial condition for the spindle, ready to be stretched again, therefore the spindle in these conditions wouldn’t work perfectly. In order to detect a stretch also when the muscle is contracted, the gamma motor neuron acts in the spindle by contracting the polar portion and so the spindle will gain once again the original length, it is ready to detect a stretch now if one is applied. Thanks to the gamma motor neurons the muscle spindle has never enough time to become floppy. The spindle is capable to distinguish the gamma motor neuron innervating the dynamic bag and the one innervating the static one. 4.​ Golgi tendon organ (GTO) A sensory neuron, the red fibres, enter in the tendon and branch interdigitating orthogonally with the fibres of the tendon. When the muscle belly exerts a force on the tendon, both in isometric and isotonic contraction, the tendon is pulled, the red fibre is squeezed, the amount of the mechanical pressure is the stimulus. It acts as dynamometer – the way the force exerted on the muscle is monitored, this is an indirect monitoring of the force, as this is measured and the tendon is always committed to the force in any condition. It is a fast adapting and a slow adapting receptor, it is able to detect: -​ from tiny to large forces from the muscle -​ velocity and acceleration -​ to cover all the spectrum of forces applied – different families of Golgi tendon organs in the tendon for the different ranges of forces, the information is interpreted, and it is understood what force is applied. RECAP