Pain Flashcards

Question

Ion channels and receptors

Answer 1

A lotIon channels and receptors of these repetors are ion channels Glutaumate receptor- ligand channel Mechanacilly gated- require mechanical stimuli Voltage gated- respond to membrane voltage

Answer 2

Sodium channels play a major role in neuronal conduction and communication- Three are highly expressed in nociceptors- in primary afferent neurons- small fibres Nav1.7 Tetrodotoxin-sensitive channel (TTX)- sodium channel blocker Pain syndromes associated with mutations Paroxysmal extreme pain disorder – increased function- NaV working too well- painful redness on orfaces –why isn’t it more widespread? Congenital insensitivity to pain – decrease in function- channel doesn’t work 1.7 Found on most nociceptors Knock out ion channel- increase threshold for pain Nav1.7 knockout mice (red) show increased thresholds in thermal tests Sodium channels play a major role in neuronal conduction and communication Three are highly expressed in nociceptors

Answer 3

Nav1.8 Tetrodotoxin-resistant channel Found on most nociceptors and primary sensory neurons Major sodium channel involved in action potentials After damage, less channels on injured nerve, more on uninjured nerve- in part explanation for allodynia- uninjured nerves, expressing this channel more, more sensitive to stimuli

Answer 4

Nav1.9 Tetrodotoxin-resistant channel Found on most nociceptors and primary sensory neurons Little is known about this channel, but expression is reduced in neuropathic pain- damage to sensory neurons- could ecplain numbness May play a role in resting membrane potential maintenance-

Answer 5

Most abundant excitatory amino acid and neurotransmitter in PNS and CNS Binds to and activates ligand-gated ionotropic channels and metabotropic (G-protein-coupled) receptor

Answer 6

Ionotropic receptors- allows passage of ions- mostly calcium and sodium AMPA, NMDA, Kainate receptors- important for synaptic transimmsion At dorsal horn- transmits info into spinal cord, activating glutamate or substance P Activation generates EPSP and membrane depolarization AMPA is involved in baseline transmission; NMDA involved with plasticity (wind- up) NMDA also linked to central sensitization- sensitize to sensory neurons inc the pain sensitivity (LTP in spinal cord, dorsal horn neurons better at transmitting sensory info)

Answer 7

Metabotropic receptors Don’t allow passage of ions, activate g protein- ligand binds and causes confirmational change and release g proteins to cause different avtivation in cell Referred to as mGluRs and involved in slower glutamatergic transmission Can inhibit or enhance pain depending on location (mGluR1 and mGluR5 enhance pain in the dorsal horn; mGluR2 expressed presynaptically where they regulate neurotransmitter release and are antinociceptive). Serotonin, dopamine Axon releases glutamate, have ampa important for baseline transmission, NMDA- enhances sensitivity and communication

Answer 8

Unique and specillized channels cation channels, ligand gated, repond to thermal simulation- noxious heat TRPV1- 35-44 degress- activated and activated by chili peppers Capsacin- TRP- sensitive- acts as ligand for it TRPv1- responds to acid, changes in PH TRPA1- ion channel, ligand gated, responds to noxious cold stimulates, less than 15 * Celsius and cinnamon and garlic and mustard oil and TRPM8- responds to cool stimuli, mint, upon injury codes for more noxious stimuli

Answer 9

TRPV1 (first one cloned, 1997) Activated by capsaicin, heat (>43°C), low pH Located on Aδ fibers, but mostly expressed by c- fibers Mice lacking TRPV1- don’t respond to the stimuli TRPA1 Noxious cold detection (<15°C) Activated by menthol, garlic, cinnamon, mustard oil but also responsible for “burning” cold, Found in many of the same neurons as TRPV1 can partner up to transmit info TRPM8 Activated by menthol, low temp (<25°C) Not found in same neurons as TRPV1

Answer 10

Adenosine Triphosphate ATP plays a role in neurotransmission and neuromodulation in pain pathways ATP activates ligand-gated purinergic P2X receptors and metabotropic P2Y receptors Expressed by primary afferent neurons and second-order neurons Activates spinal microglia \atp released- causes pain, esp when already have injury

Answer 11

Inhibitory Amino Acids GABA and glycine are inhibitory amino acids- released to modulate pain Provide inhibitory tone for the spinal cord (and many brain regions) Reduce excitability limiting transmission of pain signals Glycine is strychnine-sensitive channel. Binding of strychnine prevents glycine from binding and can cause pain and muscle spasms. Reduces inhibitory pain, can also cause death

Answer 12

Opioids Inhibitory component of pain system, activation will inhibit neuronal activation Beta-endorphin, enkephalins and dynorphins Produced by large molecules that are broken down (i.e., POMC) Why do we have them- to protect us from overactivation, protecting us from pain, are activated by chemicals we have Opioid receptors Mu: ligands act at spinal and supraspinal sites- target of angalgesic drugs Kappa: Binds dynorphins and produces analgesia; activation produces dysphoria- loss of interest/enjoyement Delta: involved in emotional reactivity and anxiety Hughes after talking to butcher looked at hypothalamus and extracted chemicals- found Met-enkephalin endogenous opiod peptibe- activates opiate receptors Beta- endorphin- during exercise and stress

Answer 13

Endogenous opiod peptides Penk- differ in last AA Endorphins- highest selectivity- activates most opiod receptors POMC- pro opiod something Makes many lignads and chemicals- large gene

Answer 14

Darker= higher expression Expressed differently and bind different receptors

Answer 15

Overactive peripherial system- linked to nocioception Reduced threshold and increased excitability of nociceptive neurons in periphery Occurs following tissue injury (role of inflammatory mediators)- burn, inflammatory injury Main mechanism for Hyperalgesia vs allodynia-making more likely for those neurons to fire Many receptors, channels and ligands involved (MAPK, TRPV1, sodium channels).- shift threshold making easier to fire Experiment- skin nerve preparation- dissect skin- still attached to nerve-can injure skin and record nerve activity. Saphenpus nerve- runs up and down leg, connects with foot Look at AP firing- how nerve fire before do anything then response to heat Injure the skin- adding bradikynin- released durring inflammation, known as algegins- causes pain-activates nocioceptors start to get impulses at lower temps and more of them when get to painful stimuli ‘shoifted to the left

Answer 16

Skin-Nerve Preparation”- record nerve activity while applying stimulus, can look at ap firing Algegin- causes pain

Answer 17

2 forms of hyperalgesia Inject substance that causes sensitivity- capsacian- activates trp-v1- have a pain flare Measure sensitivity around it and in it- where don’t see physical damage vs where do Primary hyperalgesia- occurs within the flare Secpndary- outside site of injury Primary vs secondary sensitization Inc sensitivity at primary and secondary sites Meausre pain inside vs out zone- after- all sensitive Using thermal stimuli- notice a difference Site c- shows least change Secondary- only responsive to mechanical stimuli Different neurons different responses and riles Low threshold Mechanical neurons- respond to touch and mechanical stimuli, after pain involved in pain sensitivity and sensitization receive from a beta fibres, become hypersensitive to mechanical stimuli after Inc activity of peripheral neurons that lead to sensitization- sensitizing the primary afferents in peripheral system that cause and promote pain What spinal cord 2° neuron could explain the mechanical specificity of secondary hyperalgesia?- Low threshold Mechano sensitive neurons-

Answer 18

Central sensitization- changes in cns or spinal cord Thought to be main mechanism associated with chronic (clinical) pain- no detectable injury, pain persists, sensitize cns- include brain Pain typically not evoked by a stimulus or normally nonpainful stimuli Changes in the CNS that lead to enhanced pain ”Pain memory”- neurons can remember the stimuli exposed to, remember what will cause pain- LTP, better at transmitting future stimuli, takes less to send a pain response Normal- have nocioceptor responding to noxious stimuli, and low mechano responds to mechanical stimuli, little input to pain, under inhibitory control, cant cause pain neurons to fire After injury- become sensitized, and loose the inhibitory control, - inhibitory control caused by inter-neuron in spinal cord -can now cause pain neurons to fire, eliciting response in pain neurons What would result if the LTM was stimulated following injury?- now activate pain producing neurons, producing pain

Answer 19

Put electrons in spinal cord recorded ispalateral and contralateral sides of injury before and after, records neuron firing, spontaneous activity, doing nothing. Induced injury- thermal Ispalateral- inc activity- where injury is caused Also changed contralateral side- must be central sensitization- whole area not just site of injury WDR neuron- wide dynamic range- many fibres- a delta, a beta and c recording of WDR neurons in spinal cord after thermal injury to the hind paw…

Answer 20

Apply high enough capascin- kills nocioceptors, lets in too much calcium causing death and exocoticity Still have secondary hyperalgesia bc of mechanical dectectors capsaicin desensitization Does capasician cause mirror pain or secondary hyperalgesia- no if you use a high dose and kill off all the nocioceptors, but if don’t then yes doesn’t work “mirror pain”- look at other hand, have mirror pain, similar site on opposite side responsive and sensitive to mechanical stimuli, matches site around initial injury- flare

Answer 21

Temporal summation- epsp or ipsp, coming from different times, if happen close enough reach ap threshold- can inc response, longer ap, neurons get better at responding to pain, are sensitized Needs to be close together, not a potentiation, need to be close Repetive stimulation Central sensitization- can stimulate at low frequency and see response What’s the stimulation frequency?- volts over time- 1 per every second= 1. hertz

Answer 22

LTP- caused by high frequency- 100hz, contributing to sensitivity Other neurons- projection neurons- up to brain What does “STT” stand for?- spinalthalomic tract What would be the input to the LTM neurons?- a beta LTMs are relevant for pain after injury. What concept could explain why?- central sensitization Major dorsal horn projection neuron types: wide dynamic range (WDR) nociceptive-specific (NS)- from a delta and c fibres low-threshold mechanosensitive (LTM) (“silent nociceptors”)

Answer 23

Recording electrode in spinal cord Mainipulate part of foot What neuron are you measuring- respond to pinch, nociocpeptive- recording from WDR, responds to both noxious and non noxious Pinch causes reflex- makes us know that it is nocioceptive Diabetic neuropathy rat- responds to all stimuli, even nothing- spontaneous firing In diabetic- all foot is sensitive and hyperesponsive

Answer 24

CNS0 neurons only activate where receive input from, but If do ACC- any pain manipulation , its all projected to ACC

Answer 25

Brain can send signals back down to modulate pain- Reynolds took electrode in Pareaquidetrial grey- inserted current- inc activity and signalling- did surgery without anesthetic by stimulating this area- sufficient to have surgery done without rat seeming to care Thorn- stimulated PAG- measured tail flix before or after- stimulate it, become less sensitive- takes longer to cause response Gave naloxone- kicks out opiods to rats, it reversed this effect The opiod system is responsible for descending modulation- needed to be in PAG- releases endogenous opiods

Answer 26

Opiods can act at 3 points along descending pain path- PAG and spinal cord, RVM- less pain sensitivity Hypothalamus- rememeber pain and causes release of stress hormones Stress activates this system – stress induced analgesia Frontal lobe asses the danger- activates this

Answer 27

RVM- 3 cell types- Off cell- constantly firing in absence of pain- spontaneously active, become quiet during nocioceptive response, On cells- quiet until nocioceptive response then fires with pain and neutral Put electride in rvm- firing withoit doing anuthing- off cell Morphine inhibits on cells- and activates off cells, takes on cell longer to fire, have higher threshold Put heat and get nocioceptive response- recording from off and applu analgesic- activity inc, don’t get pain response Add opiod to on cell- reduces activity of on cells- dont have pain respose Naloxone blocks this effect- return to normal Why?- because of neurons connections and where recpetors are expressed- On cell- have mu opiod recpeotrs expressed on cell, inc opiods, the opiods work on the on cells, inhibiting them directly Opiod neuron in rvm- receives input from pag, can release opiods to reduce on cell acticity Off cell- don’t have opiod recpetors expressed directly on them, gaba neuron has opiod recpeotrs on presynaptic terminal, it usually blocks the off cells a bit, but with opiods, inihibit gaba and gaba cant fire to off cell, causing inc firing, enhancing off cell activity – important to know Off cell = indirect mu inhibition On cell - direct mu inhibition Off cells fire when no pain stimulus On cells fire right before and after pain threshold is exceeded

Answer 28

Posterior grey horn- Dorsal horn Substantia- layer 1 and 2- conversion of nocioceptive, under microscope- gelatin appearance What happens in spinal cord Look at spinal cord- has butterfly esc shape Within the butterfly- neurons- sensory and motor(ventral) The spinal cord is divided by cell types and cytoarchitecture Have 10 layers Most interested in dorsal part- 1-5 1 and 2- primary afferent coming in- convey nocioceptive infio- a delta and c fibres come here Some a delta go to 3 and 5 A b- sensory fibres- convey touch, pressure, vibration

Answer 29

Fasciculus gracilis Fasciculus cuneatus Tract systems Sensory info but non painful- a beta fibres Microscope image of white matter staining Everything surrounding grey matter= white matter- the neuron tract, relays pain info up into brain Fasiculus- refers to tract system

Answer 30

Another way to see spinal cord Nocioceptive activation relayed via primary afferent neurons- a delta and c fibres, synapses in dorsal horn layer 1 and 2, can be relayed and crossed over then projected up into brain Neuroceptive information crosses tp contralateral side first then goes up Sensory neuron- primary afferent- first neuron in pathway Neuron in spinal cord- projection neurons, taking the info across the brain(secondary order)

Answer 31

Pept. C Aδ Nonpept. C Aβ/Aδ Ab- 3 and 4 layers, deeper lamina layers Peptodergic c fibres- lamina 1 A delta mylentated- 1 and outer lamina Non peptidergic c- lamina 2 Goes into different layers Primary afferent comes in convey pain- 1 and 2 lamina differences based on peptidergic vs not Non painful info- deeper lamina

Answer 32

Spinothalamic tract Spinothalamic tract Major ascending spinal Nociceptive, crude touch and temperature Project from spinal cord to the thalamus What is demonstrated Info comes in synapses with one of two second order neuron- then the info is relayed, crosses over contralalttery then sent to brain Ascending- bottom up, goes upward This path demonstrated= most simple- direct projection from second order neuron into thalamus- in thalamus have tertiary neuron To get pain info into brain- need 3 neurons \break down name- get tract Spinothalamic tract codes Nocioceptive, crude touch and temp LIKES TO ASK TO DRAW PAIN PATHWAY ON EXAM

Answer 33

Lateral Spinothalamic tract Direct projection to VPL thalamus Codes sensory-discriminative qualities of pain and temperature Lots of wide-dynamic range neurons When goes into thalamus, synapses with VPL- thamalic nuclei and directs into sensory info, somatosensory cortex Important for sensory qualities of pain

Answer 34

Anterior Spinothalamic tract Project to intralaminar thalamic nuclei Also sends projections to medulla, pons and midbrain Codes crude touch and pressure Projects to nuclei collection in thalamus- intralaminar thalamic nuclei- affective responses, arousal, autonomic pain Physiological responses to pain- cortisol, sweating, inc heartbeat

Answer 35

Spinoreticular tract- more important for arousal Projects from spinal cord to reticular formation and limbic areas Axons originate in deeper laminae (VII and VIII) Important for arousal, autonomic function, emotional aspects of pain Transmits noxious and innocuous information (mechanical, heat, light touch) Prokects to reticular formation- in brainstem and important for arousal Comes in, after seconday neuron goes up- tract is connecting with neurons in reticular formation areas, along ascent activates reticular neurons- ppl with chronic pain could cause constant activation of reticular- cant sleep Activates cerebellum- coordinates movement

Answer 36

Ascending Spinomescencephalic tract Projects to the periaqueductal gray (PAG) and parabrachial nucleus Activation of PAG neurons results in descending pain inhibition Parabrachial neurons send projections to amygdala Starts out same- goes up in bundle of fibres in mindbrain it synapses and activates PAG and periadecurail gray, then sent to the amygdala- not sent to cortex- emotional aspects of pain, like fear Understand the tracts and how to draw These tracts synapse along ascent Structures in midbrain- send prokections back down to spinal cord- periadecurail gray- if synapse here sends projections back dwon to spinal cord to try and modulate incoming pain signals

Answer 37

Dorsal column Comprises direct non-nociceptive pathway Light touch and tactile discrimination Decussates at level of the medulla Fasciculus gracilis – information from lower body- found throughout spinal cord Fasciculus cuneatus – information from upper body- in upper spinal cord only collection of Fasciculus- touch, tactile info Crosses over at medulla Comes in and goes up right away until reaches medulla and then crosses over- find second order neurons here, synapse with Fasciculus Crosses over to thalamus to get to sensory neurons

Answer 38

Nonpainful info not just going anywehere in cortex- sent to specific place in homosculous Look at cortex- specific parts respond to diff sensory info This process is somatotopy- take sensory info and send it to specific region on somatosensory map May use a diagram like thois for pain pathway * Is this just for nonpainful* brainstem nuclei- spinal pathway somatosensory cortex (S1) thalamus (ventrobasal nucleus; VPL, VPM)

Answer 39

ACC and PFC- cog control of pain Brain tries to modulate incoming pain signal Escape and planning aspects of pain, pain avoidance Don’t just code for pain- criticism of pain matrix

Answer 40

Pain matrix received criticms- activate to nonpainful stimuli This study looked at insula and its activation when in FMRI, used nociocpetive stimulus vs non paindul stimuli All these sensory stimuli activated insula- important for pain and affective aspects, also codes for nonpainful stimuli Now call saliency matrix- makes aware that something is happeneing- shift in homeostatic balance, something needs your attention

Answer 41

Goal- to look and insensivity to pain- have no sodium 1,7 channel- don’t respond to pain stimuli- thought wouldn’t have activation Found that had the same amount of activation, but not experiencing pain Maybe more of a saliency matrix- stiull feel stimulus, just not perceived as pain- only two patients Loss-of-function SCN9A mutations Mechanical pain stimulus fMRI scanner

Answer 42

Correlation between social pain and acc pain. Both activate similar regions- anterior insula, dorsal ACC, look at fmri- social and physical pain activate same areas. Many things activate these regions, acetaminophen- reduces fmri activation

Answer 43

Cognitive and motivational modification of sensory input Many supraspinal sites, cell types and neurotransmitters Descending control activates PAG- in midbrain- has opiods, projections to regions that control pain, activated bu ascending signals and supraspinal structures- higher cog control structures- like ACC, PFC, hypothalamus project to PAG This system is activated by stress

Answer 44

Descending Supraspinal sites PAG and RVM integrate information coming from limbic system Limbic system (ACC, amygdala, PFC) Opioid involvement- activated by stress, dec pain and activate dopamine System is activated by stress- when stressed, activating this system so we don’t perceive pain until later- modulates pain to get finisjed stressful activtivty- ex sports players Send fibtrs down to lower brain stem structures and spinal cord

Answer 45

Descending Monoamine Modulation of Pain- Dopamine from VTA and SN (A11) projects to dorsal horn- modulating incoming pain signals Norepinephrine from LC (A5) projects to dorsal horn- modulate incoming pain signals Serotonin from dorsal raphe projects to dorsal horn These transmitters are targets of antidepressants, for chronic pain can give these to target this system, if don’t respond to other treatment these meds can dec pain Chronic pain- have overactive ascending signals and dysfunctional descending control- taking away systems ability to modulate pain

Answer 46

Spinomescencephalic tract- Blue and red lines say where it is coming from and going from- don’t need to draw both- draw in peripherial nerve with the drg enters spinal cord and synapses with secondary neuron Primary neuron first neuoron in pathway- the drg Secon order- projection neuron in dorsal horn and crosses over and ascends to brain- parabrachial nucleaus – ascends and the ascending part from the spinal cord to synapse here, but sends its own projection into the brain in the amygdala and periaquedictal grey Projection neuron- projects form one to the other over long distance All the tracts start at the same On this diagram y= synapse, circle= neuron Starts in spinal cord ends in mescencaphlon- mid brain, the parabrachial nucleus it whats activates the amygdala- indirect activation of it, does also activate rvm, activates parts of the brainstem There is simaltaneuous activation of each path, multiple paths activated to give rise to the pain experience The ascending pain signals also activate the desceninding pathways the PAG to modulate the pain

Answer 47

Pathogen-Associated Molecular Patterns Recognition of conserved aspects of the cell wall and the cell wall doesmt change for lots of bacteria and viruses Examples include toll-like receptors (TLRs)- bacteria binds and activates it TLR2 and TLR4 recognize yeast and bacteria, respectively Specific receptor types Can divide immune system into two steps- innate- from birth, highly conserved, responds in similar way to all things vs adaptive Innate immune system- needs to recognize certain bacteria and viruses Pathogen- PAMP come off pathogen to bind to specific TLR that are found on specific types of immune cells- macrophage, PMN- these immune cells have specific receptors to recognixe pathogen- pathogen producxts bind here and activate cell to have it secrete contents or activate other cells like t cells to fight the pathogen. TLR activate fight against pathogen by detecting pathogen APC- antigen presenting cell PMN- polymorphonuclear cell

Answer 48

Damage-Associated Molecular Patterns- recognize damage, cells secrete contents- need cell lyses Recognize proteins present in cytosol and nucleus of cells- the proteins normally found in cells, they bind to DAMP Examples include P2X4 and P2X7 Signal that cell has died

Answer 49

Innate immune system Recognition of pathogens based on structural conservation- for many types of bacteria, same molecular patterns activating the susyem, the system doesn’t need to learn anything, the pathogens are conserved Don’t need to build immunity to it Mast cell- allergic reactions Macrophage- releases cytokines, pro inflammatory, mast cell neutrophil and macrophage- peripheral and WBC Microglia and astrocytes- found CNS Microglia- collect garbage of CNS,activated by bacteria, yeast, chronic pain- expression of PRR for pathogens A2 astrocyte- activated when there is damage or a pathogen, react to pathogen/damage, secrete own chemicals

Answer 50

Adaptive immune system- needs to learn Recognize, eliminate and control pathogens based on prior exposure Require exposure to pathogens to be created (cells that give immunity) Types of T-cells Helper T cells (CD4+); Th1 is proinflammatory and Th2 is anti- inflammatory Killer T cells (cytotoxic; CD8+) Have virus that infects macrophage, it presents itself to other immunce cells like t cells and helper t cells- help t cells become activated so it can fight of infection, cause release of cytokines to recruit more immune cells Helper t cell present to infected cells to help body fight off the cells T cell kills off the infected cells

Answer 51

Recognize, eliminate and control pathogens based on prior exposure Require exposure to pathogens to be created (cells that give immunity) Following injuiry distinct cgabges happen to heal Satelitte glial cells- microglial found in drg Have infection for a few weeks- macrophage go down , t cells inc Microglial- critical and important for initiation and developpement of central sensitization and chronic pain, but astrocytes sustain this pain

Answer 52

Around 7% suffer from this, but theres so many surgeries, so a lot of people Many different things contribute to this- inadequate analgesia/ anesthetic during surgery Degree of nocioceptive input during and following surgery During surgery- high nocioceptive input, following surgery still significant activation, theyre continuously being activated Can block nocioceptive input at different parts through this model After surgery give analgesia once- nocioceptive comes back Give it before, blocks it during surgery, but after still have the activation Wanna provide analgesia during surgery, then continuously treat hypersensitivity, nocioceptive input still there Postsurgical pain- driven by hypersensitivity, allodynia Qualioty of life goes down, now in chronic pain

Answer 53

Low back pain For LBP, heavy lifting and lifting weights above the shoulders are risk factors Certain professions are also more at-risk (fireman, nurse, miners, construction workers)., laborious and physicaly taxin Considered musculoskeletal, but can have a neurological component (disc herniation- neuropathic, radicular pain), slipped disk- causes nerve compression, pressing on nerve Most prevellant pain condition, and most severe and debilitating- reduced QOL

Answer 54

Osteoarthritis Risk factors for knee pain include: Age, as get older inc risk being female- most chronic pain conditions being ethnic minority high impact activity joint trauma depression anxiety (stressful job) Obesity Bone rubbing on bone, soft tissue on joints wares down Rheumotoid- inflammation

Answer 55

Rheumatoid Arthritis Chronic inflammatory disorder linked to immune dysfunction, has been considered to be autoimmune disease- lupus, chrones, MS- neuropathic pain (autoimmune) Increased amount of pro-inflammatory cytokines in joint Joint pain, swelling, stiffness, joint degeneration Treatment included biologic- class of drugs disease modifying anti-rheumatic drugs Risk factors include: being female smoking certain genetic markers (HLA genes) fatigue depression anxiety obesity

Answer 56

Few specific inflamatorry cytokines released at high levels- TNFa and IL6 and IL2 Class of drugs- biologics- target these proinflammatory cytokines Humira and Simponi- targets tnfa Andministered via monthly injections – keep activation and release at bay

Answer 57

Chronic widespread pain (Fibromyalgia) Fibromyalgia is a chronic condition characterized by widespread pain in the muscles, ligaments and tendons, fatigue, and multiple tender points. Prevalence of 2-4%, more in women Not associated with identifiable injury or lesion- idiopathic condition, no identifiabkle cause and don’t understand how it develops Thought to result from changes in pain processing pathways All over pain, widespread Have extreme fatigue Have altered prain sensing regions of the brain Considered a rheumatic condition A condition that affects the joints and/or soft tissues, causing chronic pain Significant pain and fatigue But not a form of arthritis No inflammation or damage to joints, muscles, or tissues- cant measure levels of cytokines But does produce pain in soft tissues around joints and in skin and organs throughout body Structurally intact Light blue- females, higher prevelance in females and higher ages Rheumatologist- used to be sent if have pain in joints

Answer 58

Diagnostic Criteria To diagnose it Look at tender points- points within body that are more sensitive to pressure, look at pressure semsitivity in these points Need Widespread pain for at least 3 months Painful sensitivity to 4 Kg(normally not painful) of digital pressure at 11 (or more) out of 18 anatomically defined tender points- first diagnostic criteria

Answer 59

Look at fibromyalgia patients response to pressure, much more sensitive than controls Their brain activity is changed too, controls have inc acticity between amygdala, PAG, obfc, while Fibromyalgias have reduced activity These regions are important for descending pain modulation - they cant modulate pain as well

Answer 60

Headache and migraine Migraine more prevalent in women Migraine is most prevalent among Native Americans and non-Hispanic Whites, followed by Hispanic and Black individuals Triggers include bight lights, noise, eye strain, physical and emotional distress, lack of sleep, weather changes (barometric pressure, humidity), foods (cheese, chocolate, wine), strenuous exercise cause onset of migraine Many different causes to it, genetics, most of the time the vause is unknown Follows distinct stages Prodromal- before actual pain- light and sound sensitivity Aura- hour before headache, only about 20%, changes in visual perception- caused by cortical depression spreading- depolarizing spread across cortical, starts in occipital cortex Headache- usually associated with other symptoms Postdromal- everything has happened, residual effects lack of energy, irritable, fatigue, cant concentrate Migraine episode can last up to a week Migraine linked to trigymenial vascular system- blood vessel system Linked to overdilation and have substance p release

Answer 61

Acute phase :Triptans, Analgesics Taken when a migraine is experienced to reduce pain Treats pain and other symptoms after the attack has begun Prophylatic: preventative- Antiepileptics, Beta-Blockers, Antidepressants Taken on a daily basis Reduces the frequency and intensity of Attacks Prophylatic: Anti-CGRP antibodies Reduces the frequency and intensity of attacks Monthly injections injecting antobody to bind to CGRP and neutralize it, cant be released Cgrp- released in trygmenial ganglion, binds to meneges, can inc pain

Answer 62

hic pain Pain from nerve injury/damage Described as burning, coldness, “pins and needles,” numbness and itching Common in cancer, diabetes or herpes infection Nerves become overly sensitive – allodynia develops Trigemenial neuralgi- something compressing nerve- jaw pain and head pain Trigemenial ganglion- sits under brain collection of cell bodies that inervate trigmenial nerve- main cranial nerve- responsible for neck and head sensory input Dorsal root ganglion- receives from muscle, bones and joints HIV- dsregulation of peripheral nerves Reflex sympathetic dystrophy- complex regional pain- localized pain, caused by mild trauma Tumor can press on nerves, and treatment for cancer can cause neuropathy, kills nerve fibres Postherpetic neuralgia- after shingles pain- shingles virus lays dormant in DRG until reactivated in the nerve fibres, can cause damage Diabetic- nerve fibres of legs and feet start to die

Answer 63

Disease: a medical condition with a specific cause or causes and recognizable signs and symptoms- parkinsons, huntingtons Syndrome: a collection of signs, symptoms, and medical problems that tend to occur together, but are not related to a specific, identifiable cause

Answer 64

Cancer pain- specific type of pain- breakthrough pain – sustained level of background pain but times when it breaksthrough and exceeds normal amount, analgesis is usually enough to keep pain at bay, but pain breakthroughs analgesic Purdue used breakthrough pain as reason for inc analgesic dose Q. What causes cancer pain?- many things The tumor pressing on nerve fibres, lack of oxygenation, chemo,

Answer 65

Consequence of shingles Varicella virus reactivated later in life, causing a painful rash on an area of the body that is innervated by one sensory ganglion, resulting in herpes zoster or shingles. Pain persists after rash is gone due to damage of sensory neurons Pain described as burning, sharp, stabbing Where u express that rash, where virus was reactivated

Answer 66

Phantom limb pain Phantom limb- still feel body part vs. phantom pain- it hirts Area of somatosensory cortex from missing limb can be recruited to process other areas of the body Brushing different areas of the face of an individual following arm amputation produced sensations in different fingers of the phantom hand- reorganization of somatosensory cortex Caused by amputation or severance of limb Ultimate neuropathic condition, damaging lots of nerves All amputess experience phantom limb only 5-10% experience the pain Still activating somatosensory cortex

Answer 67

phantom vs. phantom pain variable onset/ persistence sensation variability- many report low level but go through severe attacks To reduce it- give feedback to areas, how prosthetic attaches to amputated- adjusts pain, need significant contact – control gate- providing input via a beta and dampening pain movement, telescoping- once have an amputation and have phantom sensation, feel like arm is there but experience telescoping- shrink and reduce into stump, due to somatosensory cortex reorganization, not receiving own input, sensation shrinks

Answer 68

Nerve fibres that are severed, clump together form tangled nerve fibres-neuroma that can fire on its own without sensrory input, if provide sensory input, something contacting a beta, can reduce activity of neuroma PLP eliminated in ≈50% of patients provide peripheral nerve/plexus block spinal block (PLP “always”gone)- 100% of the time get rid of it Involves central sensitization more than peripherial

Answer 69

Severe limb and have neuroma, have ectopic- sponatanoues firing In drg- have it firing more Peripherally- sig componenet driven by changes in DRG Ectopic firing in neuroma: 25% Ectopic firing in DRG: 75%

Answer 70

Mirror therapy Gives visual illusion and thus visual sensory input that missing limb is back and moving Associated with reversing the somatosensory cortical reorganization Place mirror in position which you can view mirror and makes it appear as though missing limb is there, tricks brain into thinking the limb is still there Missing limb, have reorganization of somatosensory cortex and mirror therapy over 8 weeks can reverse some of this Mirror therapy, helps reduce pain drastically Mental visualization and covered mirror- no changes in pain

Answer 71

Complex regional pain syndrome- reflex sympathetic dystrophy Affects localized area of body (hand, arm, shoulder) Often due to repetitive strain 1-2 % of population affected Develops in small proportion of individuals following surgery, sprain, fracture – but doesn’t need to be trauma 2 – 4 times more common in women Type I- no identifiable nerve injury and II – have nerve injury, causalgia (no nerve injury vs. causalgia) May be functional reorganization of somatosensory cortex- affected body part is warm, shiny/glossy, swollen even though usually no active inflamattion Starts w injury, which causes changes in sympathetic nerves, reorganization in brain, neurogenic inflammation- makes it hot to touch neurogenic inflammation- AP activated at end of nocioceptor, travels along axon to release NT into spinal cord- primary afferent and nocioceptors But nocioceptors form a branch, activate one, activate many along dendritic branches, travelling to end of nocioceptors and releases substance P to dilate blood vessels and plasma extraversion- leaky blood vessels, causing inflammation-neurogenic Neurogenic= originates from nerve

Answer 72

Given the right conditions, hitting knee- can cause CRPS Peripheral Sensitization- increased excitability of nerves in the peripheral system, causing more sensory info, lowers threshold Central sensitization is the same but instead happens in the CNS

Answer 73

Ketamine- antagonist of NMDA- which is crucial for LTP and memory formation Ltp- increased synaptic communication between neurons If happens in sensory neurons- more able to communicate w each other, inc pain- driven by NMDA receptors Ketamine- dissocative anesthetic