Pain Sensory System, Taste, and Smell PDF

Aurora Killi...

Aurora Killi 02.03.22 Pain sensory system, taste, and smell Nociceptive sensory system. Biological role of pain. Pain causes. Hyperalgesia and allodynia; their cause (peripheral and central sensitization)......................................................................................................................................................................................... 2 Pain types (due to mechanism of generation, due to structures involved)......................................................................................... 6 Primary and secondary pain; their relation to afferent nerve fibers................................................................................................... 9 Pain components. Nociceptive reflex. Crossed extensor reflex......................................................................................................... 11 Antinociceptive system (peripheral and central); its role.................................................................................................................. 13 Taste sensory system. Taste receptors and primary qualities. Mechanism of activation of taste receptors................................... 16 Taste thresholds. Biological role of the taste. Taste disturbances.................................................................................................... 19 Smell sensory system. Smell receptors and mechanism of their activation...................................................................................... 22 Smell adaptation. Biological role of the smell. Smell disturbances................................................................................................... 24 1  Aurora Killi 02.03.22 Nociceptive sensory system. Biological role of pain. Pain causes. Hyperalgesia and allodynia; their cause (peripheral and central sensitization) Nociceptive sensory system Pain system Receptors → free nerve endings o Sensitive to pain signals o Distributed within the skin, subcutaneous tissues, and internal organs Pathway → lateral spinothalamic tract, trigeminal pathway o Most impulses are conducted through the lateral spinothalamic tract o Impulses from head are transmitted through the trigeminal pathway Center → postcentral gyrus o Conscious feeling of pain is produced in the cerebral cortex postcentral gyrus where there is very precise topographical localization of every body part is located o Respective regions receive impulses from pain receptors in the particular body part Pathways Pathway Description Pain and temperature 1. Lateral spinothalamic tract pathway begins with free nerve endings Lateral spinothalamic tract in the periphery pathway 2. 1st order neurons synapse with 2nd order neuron in the posterior horn of the spinal cord 3. 2nd order neuron crosses to the opposite side of the white column at the level of spinal cord 4. Via the opposite side white column, it ascends to thalamus 5. From the thalamus impulses are carried to the postcentral gyrus of opposite hemisphere Touch and proprioception 1. Dorsal column medial lemniscus pathway begins with free nerve Dorsal column medial endings in the periphery lemniscus system/pathway 2. 1st order neurons ascend through the same side white column to the medullary region 3. 2nd order neurons cross to the opposite side white column in the medullary region 4. From the here, they go to the contralateral thalamus and hemisphere postcentral gyrus Pain from head 1. It carries signals to the trigeminal ganglion and further to the spinal Trigeminal pathway nucleus of the trigeminal nerve Responsible for pain signal 2. From the spinal nucleus and a little from principal nucleus, sensory transmission from the head, information is carried through the ventral posteromedial nucleus face, and cavities of the head (VPM) of the thalamus 3. From the ventral posteromedial nucleus to the respective body part area in the postcentral gyrus Spinal cord damage in lower thoracic region causes Loss of proprioreception and fine touch in the same side of the spinal cord damage 2  Aurora Killi 02.03.22 Loss of pain and temperature sensation in the opposite side of the damage Biological role of pain Biological role of pain is warning about damage or potential damage of tissues o Pain attracts out attention to the damaged tissue o Immobilize the damaged body part to let tissues regenerate o Pain also warns about potential damage o We shift our body weight between the legs while standing or sitting o We turn our body while sleeping to prevent too much compression of tissues Congenital insensitivity to pain o Inability to produce voltage gated Na+ channels specific for pain receptors o Pain signals from nerve endings are not conducted to CNS → no feeling of pain o Daily activities can lead to damage of tissues due to lack of pain feedback o High pressure on joints and tissues in certain positions → more connective tissue, joint, and bone damage than normal people Increased pain sensitivity o Genetic mutations can cause increased sensitivity of pain such as erythromelalgia o Increased sensitivity of pain endings → increased pain sensation and pain signal transmission o Skin gets red easily Causes of pain Pain is primary reception and can be caused by three types of stimuli Thermal stimuli Temperatures > 45°C and < 5 °C can cause pain Either heat pain or cold pain in tissues Thermosensitive receptors are sensitive to thermal stimuli Chemical stimuli Acids or other substances can stimulate pain Example → capsaicin in peppers Chemosensitive receptors are sensitive to chemical stimuli Mechanical stimuli Pressure, stretch, or damage of the tissues cause stimulation of pain receptors Mechanosensitive receptors are sensitive to mechanical stimuli Polymodal receptors are sensitive to several stimulus types Hyperalgesia and allodynia Hyperalgesia and allodynia are caused by left shift of the stimulus intensity response curve Normal pain sensation → black curve o Some stimuli do not cause pain o From a certain stimuli strength there is an increase in pain sensation to increased stimuli strength o At very strong stimuli, intensity increase does not give proportional increase in pain due to poor discrimination Hyperalgesia & allodynia → left shift o If tissues are damaged or irritated, the curve shifts to the left o Hyperalgesia → increased sensitivity to pain o Painful stimuli cause stronger pain than for normal person o Same stimuli intensity that caused pain before, causes more intense pain Hyperalgesia and allodynia can be observed when we are o Allodynia → pain from a stimulus that normally would not provoke sunburnt. There is increased pain sensitivity to pain in the o Previously non-painful stimuli now cause pain sunburnt area, and light o Development of hyperalgesia and allodynia is dependent on touches to the area causes pain peripheral and central sensitization 3  Aurora Killi 02.03.22 Peripheral sensitization Release of inflammatory substances in peripheral tissues Peripheral sensitization happens in peripheral tissues when inflammatory substances are released Most important substances are histamine, bradykinin, interleukins, ATP, adenosine, serotonin, endothelin, and different growth factors They are released from o Immune system cells o Endothelial cells o Damaged tissues o Platelets Inflammatory substances increase pain nerve endings sensitivity If painful stimulus is applied → higher impulse frequency sent to the brain Primary hyperalgesia 1. Through the axon reflex, pain nerve endings releases calcitonin gene related peptide (CGRP), substance P, neurokinins 2. Neurotransmitter release stimulates neighboring cells and a series of reactions in the inflammatory area 1. Proliferation of keratinocytes 2. Activation of immune system cells 3. Vasodilation in the skin → edema formation and redness in the inflamed region 4. Smooth muscle contraction in irritated region Secondary hyperalgesia 3. After some minutes, mast cell degranulation releases Primary hyperalgesia describes pain sensitivity histamine that occurs directly in the damaged tissues 4. Histamine release causes pain receptor sensitization Secondary hyperalgesia describes pain and inflammatory reactions to occur around the sensitivity that occurs in surrounding undamaged tissues. irritated region → secondary hyperalgesia Central sensitization Reorganization of impulse transmission in the central nervous system In normal sensation If we stimulate pain nerve endings → impulses are transmitted to pain pathways and causes pain sensation If we stimulate touch nerve endings → impulses are transmitted only through the touch pathways and cause touch sensation In hyperalgesia o High impulse frequency is transmitted through pain pathways → reorganization of synapses o Reorganization causes o Increased amount of neurotransmitters o Increased number of receptors on postsynaptic membrane o Loss and dysfunction of inhibitory neurons that is normally provided by pain pathways 4  Aurora Killi 02.03.22 o These changes cause hyperalgesia In allodynia o Reorganization of pain synapses also affects touch pathway o The synapse between the previously silent touch nerve terminal and the 2nd order pain neuron is sensitized, which causes o Increasing neurotransmitter amount o Increasing receptor number in these synapses o Loss and dysfunction of inhibitory neurons → decreased inhibition of pain pathway o Touch pathway starts sending more impulses to the pain pathway → allodynia 5  Aurora Killi 02.03.22 Pain types (due to mechanism of generation, due to structures involved) Pain due to mechanism of generation According to mechanism of generation and duration, pain can be divided into Acute pain → physiological pain in previously intact tissues. It is caused by sudden damage of tissues Chronic pain → pain that has persisted for longer than 3 months. Further subdivided into o Inflammatory pain o Neuropathic pain Acute pain Nociceptive pain Evoked by acute short-lasting noxious Physiological pain stimuli in intact tissue Occurs in physiologically healthy tissues Can be caused by o Cutting the skin o Heat or cool the skin o Chemical substance on skin Chronic pain Inflammatory pain Pain following tissue injury but with no Histamine, serotonin, neural injury. bradykinin, There is evidence of peripheral and central prostaglandins, ATP, sensitization → cannot be regarded as H+ ions, K+ ions, normal physiological pain growth factors, Immune system cells and damaged tissues endothelin’s, and release substances that sensitize nerve interleukins endings and increases pain impulse transmission in inflamed region Treatment by drugs Cyclooxygenase 2 inhibitors → inhibit prostaglandin production which mediates pain sensation Opioids → suppress pain impulse transmission from the spinal cord to the brain Neuropathic pain Refers to pain after neural injury. It is a pathophysiologic state accompanied by peripheral and central reorganization Neural injury can be observed o Carpal tunnel syndrome (compressed nerve fibers) o Spinal cord injury (nerve and glial cells are damaged) o Brain injuries o Thalamic stroke → one of the most severe pains a person can experience is thalamic pain Treatment by drugs No inflammation → cannot use anti-inflammatory drugs to treat it Drugs that block impulse transmission along pain nerve fibers are used o Tricyclic antidepressant 6  Aurora Killi 02.03.22 o Anticonvulsants → block calcium influx in the presynaptic terminals o Na+ channel blockers → block sodium channels and thus also pain impulse transmission o Glutamate receptor antagonists → called NMDA receptor antagonists and they upregulate in the pain pathways due to persistent pain o Opioids → stimulate antinociceptive system to suppress pain impulse transmission from the spinal cord to the brain (similar to tricyclic antidepressant) Causes of neuropathic pain Nerve fiber damage o First origin of neuropathic pain is nerve fiber damage o Peripheral nerve cut → nerve fibers grow and try reach the previously innervated region o If the nerve fibers lose their path due to closed glial spaces → nerve fibers start tangling around the place of growth o Newly synthesized Na+ channels appear in the tangled nerve endings → nerve fibers become very sensitive Glial cell damage in demyelinating diseases o Second origin can be without nerve fiber damage, but only injury of glial cells in demyelinating diseases o Demyelinated region rebuilds voltage gated Na+ channels in the membrane that has lost glial cells insulation o Increased amount of Na+ channels in the demyelinated region → nerve fiber attains increased sensitivity to pain signals Ephaptic crosstalk o No damage to pain fibers, but damage of neighboring Aß fiber that conducts touch, pressure, and proprioceptive signals o If the demyelinated Aß fiber goes in the same nerve as the pain fiber, it can crosstalk with the C fiber → increased action potential frequency sent along the normal undamaged C fiber to the CNS Pain due to structures involved Due to place of origin and structures involve, pain can be classified into Somatic → produced from somatic structures such as skin, subcutaneous tissues, tendons, muscles, and bones. Subdivided into o Superficial → from skin and subcutaneous tissues o Primary o Secondary o Deep → from tendons, muscles, and bones Visceral → produced from internal organs Visceral pain Referred pain Caused by pain receptor stimulation in internal organs Pain receptors are not so densely distributed in the internal organs as in somatic structures There are silent pain receptors that does not normally transmit pain signals 7  Aurora Killi 02.03.22 Visceral pain receptors can be stimulated in case of o Severe ischemia → decreased blood flow to tissues o Intense stretch in a region of the organ o Chemical buildup in interstitial space (majorly H+ ions) due to decreased blood flow Visceral pain is not transmitted to the cerebral cortex via its own pathways, but is rather represented as referred pain in somatic structures The cause of pain is not in the stomatic structures where pain is felt, but rather in the internal organ that refers pain to the specific somatic structure Cause of referred pain In the embryonic life → common sensory nerves develop for internal organs and somatic structures Myocardial infarction or angina is a very common problem Decreased blood flow to the heart stimulates pain endings in the heart which are normally silent These pain endings start sending impulses through the pain pathway that is normally used by the somatic structures in the left arm and left shoulder Impulses from now active receptors in the heart is translated into pain in the left hand and not in the heart 8  Aurora Killi 02.03.22 Primary and secondary pain; their relation to afferent nerve fibers Pain fibers Primary and secondary pain depends on stimulation of Aδ and C pain fibers according to the Erlanger Gasser classification Parameter Aδ (delta) C Diameter Large (1-5 μm) Small (0.2-1.5 μm) Myelination Myelinated Unmyelinated Speed of conduction 5-40 m/s 0.5-2 m/s Depends on diameter and Since they are large and They are small diameter and myelination myelinated fibers, they conduct unmyelinated fibers → conduct impulses relatively fast impulses slow Receptive field Small Large Signal about precise location of Cannot signal about very precise painful stimulus location of stimulation Primary and secondary pain Superficial pain (somatic) Primary pain Secondary pain Transmitted through Aδ fibers Transmitted through C fibers Good localization Poor localization o Aδ fibers have small receptive fields and o C fibers have relatively large receptive end precisely in the primary fields, they give many branches to the somatosensory cortex reticular formation which spreads the Short latency impulses in the brain o Aδ fibers only have a few synapses on their Long latency way they transmit impulses very fast o C fibers are unmyelinated and of small o First synapse in the posterior horn of diameter → conduct impulses very slow the spinal cord o C fibers have many synapses in the o Second synapse in the thalamus pathway to the cerebral cortex o Third in the cortex of the brain Dull pain Sharp pain o Because C fibers transmit impulses slow o Aδ fiber stimulation causes sharp-cutting and very diffuse → dull pain in the region pain in tissues involved (also due to antinociceptive syst.) Selective cut of Aδ and C fibers The role of Aδ and C fibers in primary and secondary pain generation, can be determined by selective cut of these fibers Both fibers intact o Both primary and secondary pain intact o We will have very sharp primary pain at first + o After longer latency dull secondary pain develops + Aδ fibers cut o If we cut the large and myelinated pain fibers → o Sharp primary pain disappears - o Long-term dull pain remains + C fibers cut 9  Aurora Killi 02.03.22 o If we cut unmyelinated C fibers → o Sharp primary pain remains + o Dull pain after longer latency disappears - 10  Aurora Killi 02.03.22 Pain components. Nociceptive reflex. Crossed extensor reflex Pain components Reactions in the body that take place due to pain receptor stimulation Component Function Sensory First is the sensory component Subjective feeling of We can tell when we are in pain and where it is due to sensory component pain Produced by impulse transmission through the lateral spinothalamic pathway or trigeminal pathway to the cortical centers which give conscious sensation of the pain Cognitive Pain impulses are also transmitted to the limbic cortex Classification of pain Thus, we can classify and evaluate pain and compare it to previous painful experiences in our memory Affective Related to impulse transmission in the limbic system structures Limbic structures are responsible for regulation of emotions and behavior Pain usually causes negative emotions Autonomic Related to pain signal transmission from the spinal cord into the hypothalamus Hypothalamus is the highest autonomic center and mainly stimulates sympathetic reactions due to painful signals Person in pain has higher heart rate, breathing rate, blood pressure, pupils will dilate, person will be sweating more due to the sympathetic effect Motor Pain signals also goes to the somatic nervous system which innervates skeletal muscles This causes tension increase majorly in flexor muscles to protect painful part of the body from movement and mechanical irritation Nociceptive reflex and crossed extensor reflex In extremity that receives nociceptive input → nociceptive reflex activated 1. Pain receptors send impulses to the spinal cord 2. Motor neurons that innervate flexor muscles are activated → flexor muscle contraction 3. At the same time, inhibition of extensor muscle motor neurons takes place → extensor muscle relaxation 4. Extremity flexes In the opposite extremity → crossed extensor reflex activated 1. Activated pain fibers stimulates motor neuron in the opposite extremity that innervates extensor muscle → extensor muscle contraction 2. Flexor muscles motor neurons are inhibited → flexor muscle relaxation 3. Opposite extremity is extended to provide good support for the body and prevent further contact with the painful object and increasing the damaged site Evaluation of pain All 5 components signal to the person themselves that there is something wrong Last 4 components can be used to evaluate the pain o Cognitive → the person can transfer his cognitive component to you by classifying the pain on a scale from 0-10 o Affective → through the emotional activities of the person, we can evaluate if the person is in pain 11  Aurora Killi 02.03.22 o Autonomic → autonomic reactions in the body can indicate that the person is in pain even if they don´t say so o Motor → motor activates can help of determine if the person is in pain. If he/she is in a flexed position or if an extremity is flexed and less mobile 12  Aurora Killi 02.03.22 Antinociceptive system (peripheral and central); its role Antinociceptive system Works against pain signal transmission Decreases pain sensation after the nociceptive system has used its warning signal role This is also why secondary pain is dull Enables us to move away from the pain producing place or space Takes several steps to decrease further organ or tissue damage Divided into two parts o Peripheral antinociceptive system → large diameter myelinated non-pain fibers inhibit impulse transmission from the pain fibers to the CNS. o Central antinociceptive system → descending nerve fibers from the brain that decrease pain impulse transmission from the spinal cord to highest centers of nociceptive system Peripheral antinociceptive system Pain pathway→ C fibers 1. Pain signals are transmitted through unmyelinated C nerve fibers 2. These fibers begin from free nerve endings and carry impulses to the posterior horn of the spinal cord where they + Activate 2nd order neuron which send impulses through the lateral spinothalamic tract - Inhibit the inhibitory neuron that before stimulation of pain receptors was causing inhibition of the pain pathway 3. So, when pain receptors are stimulated, pain signals are transmitted to the brain Touch-pressure pathway → Aß fibers 1. If touch and pressure conducting myelinated Aß fibers are activated in We can rub the skin area or the same region as pain endings press on the painful site to Impulses are sent through the dorsal column medial lemniscus stimulate touch-pressure system to the brain about the touch nerve endings and suppress + At the same time, signals from touch pathway will activate pain sensation. Acupuncture and massage on certain points inhibitory neuron in the dorsal horn causing inhibition of impulse in the skin can suppress pain transmission in pain pathway impulse transmission + Touch pathway has excitatory but low activity synapses with the pain pathway. 2. In general, when touch and pressure nerve endings are stimulated in the periphery → impulses conducted to the dorsal horn will strongly activate the inhibitory neuron, and thus - inhibit pain impulse transmission to the CNS. Central antinociceptive system Related to the brain´s ability to suppress pain signal transmission to the pain centers 1. When nociceptive system is activated, it transmits signals to the brain centers 2. On the way to the highest center, pain signals are also sent to the brain stem structures Limbic system structures (limbic cortex, amygdaloid nucleus, hypothalamus) Periaqueductal grey matter Raphe nuclei, locus coeruleus 3. Brain stem structures activate due to pain signals 13  Aurora Killi 02.03.22 4. Limbic system makes the emotional and cognitive response to pain signals, so if the person is in a safe environment e.g., with doctors → limbic system structures send impulses to the periaqueductal grey matter in the midbrain 5. Dopamine and opioid peptide secreting neurons in the periaqueductal grey matter stimulates medullary region Raphe nuclei Locus coeruleus 6. Raphe nuclei releases serotonin, locus coeruleus release norepinephrine 7. Serotonergic and norepinephrinergic pathways activates inhibitory neuron in the dorsal horn → inhibit impulse conduction along the pain pathway Drugs affecting the antinociceptive system Central antinociceptive system We can apply specific medications for the pain if we cannot treat it with anti-inflammatory drugs or local anesthetic solutions that blocks Na+ channels Opioid peptides o We can apply opioid peptides exogenously by injecting it or using skin patches o Enkephalins o These will activate the receptors in the brain stem stronger than natural opioid peptides do Cannabinoids o Similar mechanism is for cannabinoids like substances found in marihuana o They also suppress pain sensation Tricyclic antidepressants o Can be used in some types of pain that does not respond to other medications o These drugs increase dopamine, serotonin, and norepinephrine amount in synapses by inhibiting their breakdown o Stronger inhibition of pain impulse transmission Selective serotonin reuptake inhibitors o Can inhibit serotonin reuptake in the central nervous system synapses, providing stronger inhibition of pain impulse transmission Pain stimulating systems There are also pain stimulating systems Histamine and acetylcholine system can increase impulse transmission through pain pathways If the person is not in a pleasant environment where he/she is taken care of by the doctor, it can cause activation of histaminergic or acetylcholinergic reticular formation nuclei This can increase pain impulse transmission Peripheral antinociceptive system Cyclooxygenase inhibitors o Inhibit production of inflammatory mediators like prostaglandins, thromboxane’s, leukotrienes o By this they decrease the stimulation of peripheral nerve endings in the inflamed region Local anesthetics o Can block impulse transmission along the nerve fibers o Used in the dentistry or wound closing procedures in the skin o Decreases pain impulse transmission along the nerve fibers Na+ and Ca2+ channel blockers 14  Aurora Killi 02.03.22 o Drugs that block Na+ and Ca2+ channels in the synapses of the nociceptive pathways might be of help to treat persistent pain 15  Aurora Killi 02.03.22 Taste sensory system. Taste receptors and primary qualities. Mechanism of activation of taste receptors Taste sensory system Taste is chemical sense Secondary reception (specialized receptor cells) Taste receptors Taste receptors are modified epithelial cells located in the taste buds Taste buds are located on papillae that are scattered all around that tongue Three types of papilla that contain taste buds o Fungiform papillae o Mostly distributed in the anterior 2/3 of the tongue o Foliate papillae o located on sides of the tongue o Vallate papillae o Located at the back of the tongue in a V-shaped row o Vallate papillae contains around 50% of all the taste buds on the tongue o On each vallate papillae can be around 250 taste buds Each taste bud contains taste receptor cells that protrude their microvilli towards the taste pore Saliva with dissolved substances can enter the taste bud through the taste pore and stimulate taste receptors Supporting or sustentacular cells are located around taste receptor cells and provides support and play a role in taste sensation Basal cells regenerate taste receptor cells → it takes approx. 7 days to regenerate the receptor cells after taste bud damage Taste pathway Taste receptor cells are connected to afferent nerve fibers of the gustatory nerves Three nerves conduct impulses from the taste receptors to the CNS o Facial nerve (VII) carries impulses from the anterior 2/3 of the tongue o Glossopharyngeal nerve (IX) carries impulses from the last and deepest 1/3 of the tongue o Vagal nerve (X) carries impulses from taste receptors in epiglottis Signals from all three nerves meet in the gustatory nucleus located in nucleus tractus solitary Nucleus tractus solitary carries information further into the ventral posteromedial nucleus of the thalamus and from there impulses reaches the cerebral cortex Taste area in the cerebral cortex is located in o Insula and o Lower part of the primary somatosensory area in the postcentral gyrus where tongue sensory area is 16  Aurora Killi 02.03.22 Taste qualities There are five taste qualities that our receptors can sense → sweet, sour, salty, bitter, and umami (delicious) Receptor cells Each receptor cell is specialized to sense one of these qualities (other substances can also mildly activate them) o Receptor cell 1 → salt taste receptor o Mostly activated due to NaCl or salt taste o Activated a little by HCl or sour taste o Receptor cell 2 → sour taste receptor o Mostly responds to the HCl or sour taste o Activate a little by salty and bitter taste (quinine) o Receptor cell 3 → sweet taste o Activate due to sucrose or sweet taste Each receptor cell conducts impulses separately via the nerve fiber that it contacts with → makes us differentiate in between these taste qualities Other tastes are made due to mixed activation of different receptor cells → more complex taste qualities Distribution of taste receptors The five taste qualities can be determined all of the tongue, but for each quality there is a certain part of the tongue which is the most sensitive to it Sweet and umami taste → most receptors are located at the tip of the tongue Sour and salty taste → receptors mainly located on the sides o Salty closer to tip o Sour deeper on sides of tongue Bitter taste → the bitter taste receptors are more densely distributed at the radix of the tongue Mechanism of activation of taste receptors Taste qualities connected to ion flow through apical membrane Salty Caused by salts that dissociate into anions and cations NaCl or table salt is Cations have the major role in activation of receptor cells the most common Anions can also activate them salty substance Mechanism of activation 1. Receptor activation is related to Na+ influx through epithelial Na+ channels Similar to those in the distal convoluted tubule Can be blocked by K+ sparing diuretics 2. Na+ is in greater concentration in saliva and flows into the receptor cell → depolarization 3. Depolarization opens voltage gated Ca2+ channels and Ca2+ influx → neurotransmitter release in synapse with afferent fiber 17  Aurora Killi 02.03.22 4. Neurotransmitter binding triggers excitatory postsynaptic potential generation → if threshold is reached, action potentials are generated and conducted to the brain stem Role of anions Sodium bicarbonate tastes salty, but also a little bitter That means that not only cation determines the taste of the salt, but the anion also has a certain role Anion sensation is thought to be provided through the sustentacular cells These cells also can influence impulse transmission to the CNS Sour Produced by acids that dissociate into H+ ions Organic acids (some) can diffuse through the apical surface and then dissociate inside the receptor Inorganic acids dissociate in the saliva and tastes less salty Mechanism of activation 1. H+ ions flow through non-specific cations channels into the receptor 2. H+ ions block K+ channels in the apical membrane, inhibiting K+ outflux → depolarization 3. Depolarization opens voltage gated Ca2+ channels in the cell membrane 4. Ca2+ influx stimulates neurotransmitter release in the synapse with the afferent nerve fibers Taste qualities related to second messenger generation Bitter These taste qualities have different receptors, but the general mechanism is the Ions (K+ and Mg2+) same Organic substances 1. Substance (bitter, sweet, or umami) binding to (long-chain nitrogen receptor on the taste receptor cell → G protein containing stimulation activates phospholipase C substances and 2. Phospholipase C converts phosphatidylinositol alkaloids) bisphosphate (PIP2) into inositol triphosphate (IP3) Sweet and diacylglycerol (DAG) Sugars 3. IP3 and DAG opens Ca2+ channels in Alcohols (sorbitol) Aldehydes, ketones Smooth endoplasmic reticulum Amino acids Cell membrane (aspartame), 4. Ca2+ concentration increase → neurotransmitter proteins release in synapse with the afferent nerve fiber Umami L-glutamate Bitter taste receptors Out of the receptor number on taste receptor cells → bitter taste receptors are superior Around 30 different genes encode bitter taste receptor on the receptor cells Bitter taste receptors are most commonly observed genetically defective 18  Aurora Killi 02.03.22 Taste thresholds. Biological role of the taste. Taste disturbances Taste thresholds Taste thresholds differs between the taste qualities due to the biological role of the taste system → it defends and also regulates food intake Taste quality Threshold Explanation Bitter 10-6 mol/L Lowest threshold Many bitter plant alkaloids are poisonous to humans Low threshold → recognize bitter taste faster and stop eating these foods Sour 10-4 mol/L Second lowest threshold Acidic taste can indicate that the food is spoiled, thus low threshold Umami 10-4 mol/L Similar threshold as sour Helps us to recognize amino acids and proteins a little bit easier Salty 10-2 mol/L Salty and sweet taste qualities have relatively high threshold It is kept relatively high to maintain normal intake of salts Salts are necessary for regulation of o Excitability of different excitable tissues o Fluid compartments in cells, interstitial space, and blood vessels Sweet 10-1 mol/L The highest threshold is for sweet taste High threshold to provide normal intake of carbohydrates Carbohydrates are the main source of energy production Factors that affect taste thresholds Taste thresholds upon different situations might change Factor Effect Functional state of receptors, Receptor damage → decreased taste sensation in the area until pathways, and centers receptors regenerate o Drinking too hot drinks Receptor dysfunction might also be caused by tumors or infections on the tongue Taste nerves or center damage → loss of taste perception o Due to tumors of the CNS o Stroke damaging certain regions of brain Adaptation Short term adaptation o Adaptation can increase taste threshold for a particular taste o Taste of substances is better at the beginning of eating o If the same substance concentration is kept in the oral cavity, adaptation happens within a minute o Adaptation is does not only happen in the oral cavity o Impulse transmission to the brain stimulates adaptation of the pathways of gustatory sensation Long term adaptation o Adaptation can also change taste thresholds in long term o If we eat a lot of salty food → salt threshold increases o If we do not eat food or a certain type of food → taste threshold might decrease 19  Aurora Killi 02.03.22 Secretion intensity of saliva Optimal saliva secretion is the best for taste sensation Decreased saliva secretion → decreased taste perception o Substances cannot dissolve effectively o Not easily delivered through the taste pore to the receptors o Taste sensation decreases Overproduction of saliva → decreased taste perception o Substances are diluted in the saliva o Their concentration decreases on the way to the taste receptors o Taste sensation decreases Temperature of food Temperature changes speed of ion diffusion through the membrane Increased temperature of food → increased Na+ and H+ ion influx into receptor cell thus stimulating taste sensation (threshold decreases) Decreased temperature of food → cold food taste qualities are determined worse (threshold increases) Activity of smell receptors A lot of taste perception realized through o Smell o Memories of taste Blocked airflow through nasal cavity → taste intensity decreases Smell receptors are important in taste perception Biological role of taste 1. Allows sorting of food that enters oral cavity Enables us to determine the quality of the food If the food is good enough to swallow or not 2. Stimulates secretion of gastrointestinal juices Regulation of gastrointestinal activity Nucleus tractus solitary is responsible for stimulation of secretory function in o Oral cavity o Stomach and small intestine (afterwards) Taste prepares gastrointestinal tract for the food that is coming through the oral cavity 3. Regulates food intake Taste receptors activate satiety center in hypothalamus Impulses from the taste receptors are also sent to the orbitofrontal cortex This is where our preferences of food are regulated and thus also our eating behavior Taste disturbances If the taste system does not work properly, it leads to taste disturbances Absence of taste → ageusia o Caused by central nervous system damage o Either pathway or center destruction o Leads to total loss of taste Decreased sense of taste o Partial loss of receptors, nerves, or center damage → decreased sense of taste o Vitamin deficiencies → vitamin B12 deficiency can cause decreased taste sensation o Endocrine abnormalities → diabetes mellitus can cause decreased taste sensation o Saliva secretion problems → increased or decreased saliva secretion will cause decreased taste o Teeth or tongue problems → inflammatory processes in the oral cavity can decrease sense of taste Disturbed sense of taste 20  Aurora Killi 02.03.22 o Can be caused by bacterial products produced due to inflammation in o Inflammation in oral cavity mucus membrane o Carious teeth o Miracle fruit o Contains miraculin that changes taste qualities o Miraculin can activate sweet taste receptors if pH of saliva is low o Sour foods → sweet taste o Will not have this effect in neutral pH 21  Aurora Killi 02.03.22 Smell sensory system. Smell receptors and mechanism of their activation Smell sensory system Chemical sense provided by secondary reception Receptors → modified nerve cells o Smell receptors are modified nerve cells o Located in upper nasal cavity in olfactory epithelium o Protrude their cilia into the mucus that covers the olfactory epithelium o Mucus is secreted from Bowman´s glands and goblet cells that are distributed in between the receptor cells Pathway → olfactory nerve (I) o Axons of olfactory receptor cells forms the olfactory nerve (I cranial nerve) o Olfactory nerve protrudes through the cribriform plate opening into the brain o They synapse with mitral cells in bulbus olfactorius o Impulses are further transmitted into the CNS centers Center → uncus o The main center is located on the medial surface of uncus of the big hemispheres Olfactory epithelium Epithelium in nasal cavity is covered by mucus secreted from Bowman´s gland and goblet cells Mucus layer is thick and entrap substances in air and transports them to the cilia of the receptors Olfactory binding proteins in the mucus transports hydrophobic substances from the air through the mucus to the receptors Olfactory epithelium also contains o Sustentacular cells → supports receptor cells o Basal cells → regeneration of olfactory receptor cells Receptor cells are constantly renewed o About 4-8 weeks until olfactory receptor cells are restored after their damage o Takes long time because it is not so easy for axons that go through the cribriform plate to find the previous glomeruli where they synapsed o Smell sensation might not recover fully after damage of olfactory receptor cells Range of smell Human smell system is not very sensitive compared to other mammals Area covered by olfactory epithelium → 10 cm2 o Rats → 15 cm2 o Cats → 20 cm2 o Dogs → 150 cm2 (300 cm2 for specific breeds) Humans have rather small area of receptors cells, thus sensitivity of smell system is low Olfactory receptors Substance transport to cilia o Hydrophilic substances dissolve in the mucus and are caught by cilia of receptor cells 22  Aurora Killi 02.03.22 o Hydrophobic substances are transported to the cilia by olfactory binding proteins Genes o Thousands of genes determine receptors on olfactory cells o Only 400 of these genes are functional, thus we have 400 different receptors on olfactory receptor cell Smell sensation o Each receptor cell is specialized to sense certain substances in the external air o Receptor cells that have the same receptor converge on the same glomerulus in the olfactory bulb o Impulses carried from the olfactory bulb send information about the particular sense of smell o Granule cells located in between glomeruli on the olfactory bulb, provide lateral inhibition on neighboring cells o Lateral inhibition increases discrimination of the substance that we smell Mechanism of activation of smell receptors Smell receptors are connected to second messenger generation in the cell 1. Substance that come to the receptors located in the cilia should be in vapor form 2. Then it binds to the receptor → G protein and adenylyl cyclase activation stimulates cAMP generation 3. cAMP opens non-specific cation channels Ca2+ ion influx (mainly) Na+ ion influx (a little) 4. Ca2+ ions stimulate Cl- channels in the cilia → Cl- outflux In most cells → [Cl-] inside < [Cl-] outside In the olfactory receptor cells → rather low [Cl-] outside Low Cl- concentration, electrical charge of Cl-, and negative membrane potential provide Cl- outflux 5. Ca2+ and Na+ influx + Cl- outflux → depolarization of cell 6. If threshold in axon hillock is reached, action potentials are generated and delivered to glomeruli of olfactory bulb via fila olfactoria that goes through the cribriform plate Pathway Pathways that conduct information about the substances reaching the olfactory epithelium into the brain Olfactory receptor cells send impulses through the cribriform plate into the olfactory bulb In the olfactory bulb they synapse with glomeruli 2nd order neurons carry impulses to Olfactory cortex located in uncus in medial part of hemispheres and related temporal lobe structures responsible for emotional regulation and memory (we can remember situation from the smell) Some impulses go to orbitofrontal cortex through the mediodorsal nuclei of thalamus. The orbitofrontal cortex makes us to prefer certain smells over others. 23  Aurora Killi 02.03.22 Smell adaptation. Biological role of the smell. Smell disturbances Smell adaptation Smell system is fast adapting system o During first seconds → smell sensitivity decreases to half o After 1 minute → almost complete adaptation Smell system warns us about threatening substances in polluted air o In case if we are not able to leave the place, smell system adapts and by that let us stay 1. Ca+ ions that flow into the receptor cell bind to calmodulin 2. Calcium-calmodulin complex causes feedback inhibition on the Ca2+ and Na+ channels 3. Ca2+ and Na+ influx decreases → impulse frequency to CNS decreases as well Biological role of smell Control of chemical composition of air o Warns us about substances in the external air that might be harmful o Let us leave the place if it is polluted Facilitates taste sensation o A lot of taste perception is done through smell receptors o Taste perception can be produced either from o Smell of the food in the external air o Chewing process in which substances in vapor form can ascend to the nasal cavity through the nasopharynx Regulation emotional state o Smell qualities regulate our mood o Pleasant smells → good mood o Unpleasant smells → bad mood o Smell sensory system is closely related to the limbic system o Cortical centers of the smell system included in the limbic system which regulates our behavior Facilitates recognition of own from foreign etc. o We can recognize our objects from foreign objects through smell o Mother-child relationship is related to smell system activation o Synchronization of menstrual cycle is partially related to the smell system o To regulate the social and sexual behavior for animals, the specific wormer of nasal organ is located in the nasal cavity, which senses pheromones o Wormer of nasal organ for adult humans is rather underdeveloped, despite of that we have some pheromone receptors in the nasal cavity. Substances which activate them are not yet found Smell disturbances Smell disturbance Explanation Absence of sense of smell If receptors, pathways, or centers are damaged Anosmia Fila olfactoria that cross the cribriform plate is very tiny, and can be teared off if the brain moves too much within the cranial cavity Stroke or tumors in the brain that compress smell pathway → absence of smell Decreased sense of smell Blockage of nasal cavity o Most common cause of decreased smell sensation 24  Aurora Killi 02.03.22 Hyposmia o Running nose can obstruct air flow through nasal cavity and decrease sense of smell o Total nasal cavity obstruction may cause complete loss of smell Age and sex o Physiological decrease of smell sensation o After 60 years → smell receptor number progressively decreases o Females have a little better smell than males o Both sexes have aging related decrease of smell Partial damage of epithelium, nerve, pathway, or center o Decreased sense of smell can also be observed by partial damage of the olfactory epithelium, olfactory nerve, or pathways and centers in the brain Parkinson´s and Alzheimer´s disease o Early sign of neurodegenerative diseases such as Parkinson´s and Alzheimer’s disease o Smell decrease occurs before the mental and motor disturbances Covid-19 o Decreased smell sensation due to SARS Cov-2 virus infection o Virus does not affect receptor cells in the olfactory epithelium (olfactory epithelium do not have angiotensin converting enzyme 2 receptors) o Receptors located on sustentacular cells and respiratory epithelium trigger inflammatory reaction → inhibition of impulse transmission from olfactory cells to CNS Smell disturbances Smell disturbances most often occur due to inflammatory reactions in nasal, paranasal, and oral cavity Bacteria related products can stimulate olfactory epithelium without any presence of substances in the external air 25