so in this video we're going to take a quick look or maybe not a quick look but a look at pain so pain can be described as an unpleasant sensory and emotional experience associated with tissue damage or potential tissue damage or described in terms of tissue damage now that's quite a big definition of pain and this is the definition that's used by the International Association for the study of pain there are some other definitions out there but I think this definition nicely encompasses everything that has to do truly with pain so for example you see that it's an unpleasant obviously sensory or emotional experience so this makes pain quite different to other types of sensory stimuli or sensory experiences for example such as basic touch or sight or sound or taste in which the emotional component doesn't heavily alter the experience but when it comes to pain the emotional component truly does alter the experience I'm going to get to that point when we talk about descending inhibitory pathways so now that we've got the definition at the road let's look at pain and the pain pathway and how it all works together with the central nervous system so I think the first thing we need to have a look at some of the triggers for pain so we know that we've got fine touch or two-point discrimination touch now this will travel to the brain via a different pathway than the pain and temperature pathway so first thing you need to be aware of is that pain and temperature basically piggyback on one another when it comes to being sent from the external environment or internal environment to the brain it's different to that on the simple fine touch or two-point discrimination touch they go to the brain together through a different pathway so what type of stimuli triggers pain that's the next question well pain can be triggered pain can be triggered by mechanical stimuli paying could be triggered by thermal stimuli so temperature or it can be triggered by chemical stimuli so mechanical thermal and chemical are the three stimuli for pain now what you're going to find is that when we look at receptors for pain so obviously you need a receptor to pick up a stimulus for paying these receptors are free nerve endings so remember that your nerves are going to have been myelinated what you're going to find for pain is that the receptors are free nerve endings and they're unmyelinated they're not encapsulated with certain types of connective tissue they are just free no nerve endings so we can say free nerve endings and there's basically two main types of fibers that pick up pain and these two main types of fibers are what we call a delta fibers and c fibers now a delta fibers that both are thin in diameter so they're both thin fibers now when I say thin that's that's a comparative term it's thin in comparison to the fibers that send normal touch or fine touch stimulus to the brain so these are thin fibers they're all so poorly myelinated which means they don't have a nice sheath surrounding them you'll find that that a delta fibers poorly myelinated and so are the C fibers but they're even less so so we can basically say that they're unmyelinated so both are thin fibers both are poorly myelinated or unmyelinated and what you'll find is that a delta fibers they send a relatively fast signal or at least compared to C fibers they send a fast signal and C fiber send a slow signal how fast well around about 15 or so m/s and for slow its around about half a meter to a meter per second now why do we have two different types of signals sending pain or fibers sending pain to the brain one that's quick one that's slow well what you'll find is that the a delta fibers the type of signal that they send quick sharp stabbing pains and the C fibers they send slow dull aching pains and this makes sense when you stub your toe in the middle of the night you'll kick something you'll first experience the first pain which is the fast one that's going to get to your brain faster you experience a sharp stabbing pain and that tends to subside relatively quickly and then what takes over is this slow dull aching pain so what I want to talk about is the fact that I'm going to show you the pathway that these two fibers take to the brain and what they do in order to alter your emotional state as well and also result in you experiencing pain so when it comes to these three stimuli stimulating these two different types of fibers what you're going to find is that even though these are the three stimuli there's three main types of receptors now you may say yeah mechanical thermal and chemical but in actual fact the receptors that pick up these stimuli one is what's called a high threshold high threshold mechanical another one is called a mechanic Oh thermal receptor mechanic Oh thermal and another one is what we call a poly modal so of these three stimuli what do these receptors pick up well the first one which is a high threshold mechanical obviously picks up a mechanical stimulus but it's high threshold now what does that mean well you know hopefully you know that when you need to send a signal through a neuron it needs to stimulate an action potential and an action potential needs to hit a particular threshold in order for it to occur so for example for most neurons it's around about negative 55 millivolts this is the difference the threshold that meets that reach before it can send an action potential now higher thresholds mean that it's not going to be negative 55 it's going to be somewhere higher than that now what that means is it takes more positive ions to influx to stimulate it okay so with normal touch right with normal fine to point discriminative touch such as that of being able to feel that I'm holding this pen then low threshold mechanical stimuli so it doesn't take much to stimulate the mechanical receptors because mechanical receptors require some sort of mechanical force or depression on the receptor and this alters its conformational that sodium ions rush in there low threshold which means that you don't need many sodium ions to come in to send a signal to my brain and I go oh I'm touching something right but when it comes to these high threshold mechanical fine pressure or reduced amount of pressure isn't sufficient you need a fair bit of pressure and that's why you've got this delineation between fine touch and then if something pushes very hard it can be quite painful because that's now triggering there's high threshold mechanical receptors you require more sodium influx in that area mechanical thermal will they simply pick up mechanical force and temperature and poly modal actually picks up all three paths mechanical thermal and chemical when it comes to a delta fibers and C fibers what type of receptors do they have well what you'll find is that the a delta fibers will have high threshold mechanical receptors and Mackenna co thermal and that the poly modal receptors are those of C fibers okay so far what have you learned you've learnt that pain neurons have free nerve endings okay so they're not encapsulated at the end or covered in myelin there's two main types of fibers that are connected to these receptors they see fibers and a delta fibers a delta a faster for a sharp stabbing pain and C fibers are slower for a slow dull aching pain the type of stimuli that can trigger pain fibers mechanical thermal and chemical and they can trigger receptors via high threshold mechanical mechanical thermal and poly modal now what we need to talk about is draw up the spinal cord and show how pain can get to the brain differently to fine touch and talk about some clinical implications all right so let's now draw up a cross-section of a spinal cord so let's now draw up a cross-section of a spinal cord okay now couple things this is a transverse section so we're looking in we've got the gray matter here where the central canal there we've got white matter here and you're going to have obviously your dorsal nerve root with the dorsal root ganglia and your ventral nerve root and they come up to form a fixed nerve as we're aware and that's your spinal nerve and obviously you have pairs of spinal nerve so it's going to happen on the other side as well but we're not going to worry about that at the moment ah now couple things is first thing is that you know that the white matter which sits out here they're simply the highways they just send the signals so they're going to send signals up or they're gonna send signals down if we have a look at a spinal cord and have a look at these tracks what you're gonna find for example is that there's going to be white matter tracks at the back here and these white matter tracks will send signals up to the brain so therefore sensory input and these white matter tracks are here for fine touch they're called the dorsal column right they're there for fine touch two-point discrimination and proprioception okay it's actually called the dorsal column medial lemniscus pathway I've done another video on that so please feel free to watch it you're going to have pathways here that are coming down on that side and on this side and this is going to be from motor so it's going to send a signal out and this is the cortical spinal pathways and this is from motor now it's actually motor predominately for the limbs for example and you'll find that here you've also got motor pathways at the anterior aspect and this motor is more so for the axial so the the axial musculature so that's going to be the the thorax and the torso and so forth and then here you're going to have I should change the color I think i sinning will be in bloody sinning wall being read and you've got a sending pathways here and this is for pain and temperature and this is called the spinothalamic tract and that's what we're going to focus on so we're not going to talk about any of these descending motor pathways so we're not going to talk about what's happening up here or down here we're going to talk about firstly fine touch get into the brain and pain and temperature get into the brain and how it works differently okay so these are the white matter tracts first of all so now let's draw it back up and talk about touch getting to the brain so get our cross-section of the spinal cord alright and we're gonna have the dorsal nerve right ventral nerve throat coming together to form a mixed bottle nerve dorsal root ganglion okay now let's just say that this is my finger and the nerve the neuron for fine touch is coming into my arm into the spinal nerve which is this here and we know that it must go through the dorsal nerve very all sensory input goes with a dorsal nerve root all motor comes out the ventral nerve root so you need to know that first of all and then it's going to come in to the dorsal gray horn all right so let's make fine touch in blue so something is triggered so fine touch let's say it's my finger something has triggered that neuron and it sends an action potential in through the spinal nerve up through the dorsal nerve root that's the dorsal root ganglion a ganglion is where cell bodies sit outside of the central nervous system alright it continues in it goes into the spinal cord at the door gray horn and what happens with fine touch is that this neuron jumps into this dorsal white matter and it starts to move up towards the brain so now what we need to draw is a little bit of the spinal cord then we need to draw the brainstem and in the cerebrum so we've got a bit of the spinal cord here and here and now we're going to go to the medulla and then the pons and in the midbrain and then we go into the cerebrum okay so what's going to happen actually let's let's just draw this a little bit lower so that I can show you more so what happens at the cerebrum medulla pons midbrain medulla pons midbrain cerebrum cerebrum let's drop the film eye which is there in the diencephalon we'll talk about that in a second okay so what's happening here the touch signal has just come from my finger it's going in the dorsal nerve root it goes into the dorsal gray Horn jumps into the dorsal white matter here goes up these tracks continues up until it gets to the medulla so let's label this you've got the midbrain you've got the pons and you've got the medulla and we know together that's the brainstem this is the cerebrum cerebral hemispheres and these are our thell am i okay athol um I talked about that in the same so the touch signals going up once it gets to the medulla this is where it's sign APS's with a second neuron now here at synapse is with the second neuron and it decussate meaning it crosses over to the other side of the spinal cord so that means that when you have a sim pull touch fine touch coming into my hand for example down my arm into my spinal cord it goes up to the brain the same side in which it came in okay and at the medulla which is the lowest aspect of the brainstem that's where it's synapse is with a second neuron and deca sites which is a term we used for crossing over to the other side of the brainstem and then continues to a send and goes to the thalamus now why are the thalamus because the thalamus is the sorting center of the brain and it takes sensory information and it decides what to do with it you guys okay am I going to send it to this part of the cortex this part of the cortex maybe after the limbic system maybe somewhere else so it's the sorting Center just like the post office and it decides okay I'm going to send this signal to this part of the cortex which is associated with the hand for example so what you can see is that a sending sensor information is a three neuron chain for fine touch it's one to the medulla to to the thalamus three to the cortex now you're probably watching this going I don't care I'm here to talk about pain well let's now look at the pain pathway let's now say that it's coming from the mouse the same finger that had the phone touch the tickle with the feather for example and now we're stimulating nociceptors nociceptors are the pain receptors remember I spoke about those pain receptors high threshold mechanical mechanic Oh thermal and also the poly modal we're stimulating that at my finger maybe with a pinprick and we send a signal down remember the a delta and C fibers and it's coming in because it's sensory it still goes through the dorsal nerve root goes into the dorsal gray horn and a couple things might happen first of all if it's an a delta fiber what you'll find is little synapse very very early in this dorsal gray horn so let's just say it is an a delta fiber the fast one it will synapse in the first two couple of layers here these Rex layers of the Rex laminar layers of the dorsal gray horn maybe what or three or one or two and it's I lapses here with the second neuron so this is different to touch already and it will then cross over anterior to the canal into the lateral white matter okay this lateral white matter and what it will then do is it starts to a send up a spinal cord now it bypasses the medulla and go straight to the thalamus where it signups is it must go to the felmers because all the sensory input in order for you to be aware of it must go through the thalamus and then sends a signal again to the part of the cortex associated with the hand but this time you know it's painful so what can you see you can see that compared to touch the pain signal the first still a three and you're on chain right one two three so all sensory a sending pathways are three neuron chains the first sign-ups is at the dorsal gray horn with the second neuron which decussate s-- at the level in which it entered the spinal cord crosses over goes into the white matter now probably more so into the anterior lateral white matter which is more so down here and then moves upwards and then continues to a cell bypasses the brainstem goes to the film of silences with the third neuron that then goes to the cerebrum says okay you're now experiencing pain this happens because it's a delta quickly it's a sharp pain and it goes straight to the thalamus and it's quite localized so a delta fibers will give you a localized relatively specific pain you know it's coming from your finger for example okay how is this different to a see father well let's now just pretend that this red path way we've drawn is now a see father as opposed to an a delta fiber okay it's still going basically via the same pathway to the brain now the a delta fibers are usually known as the neo spinothalamic pathway so what I want to write up now this the pain pathway is called the spinothalamic pathway and now you can see why because it goes from the spine to the thalamus right spider thelma's the spinothalamic pathway that's the pain pathway and you can have the Neo spinothalamic pathway neo means new or you can have the Paleo spinothalamic pathway paleo is referring to old what's the difference well the Neo is usually the a delta fibers and the paleo is usually the C fibers okay so if you hear the Neo spinothalamic path weights that fast a delta fibers quite specific and localized and then the C fibers paleo older it's a slower signal and what you'll find is it's not that localized it's more a diffuse pain so when you stab your stub your toe for example the a delta you know exactly where you stubbed your toe but then that dull aching pain afterwards you just get this general ache around your foot for example so it's poorly localized alright so now this is a C fiber coming in it's more slow about 0.5 to 1 meter a second right and as it comes up this is one of the differences instead of just sign up seeing at the thalamus and then at the cortex like the a delta fibers do there's actually branches of C fibers that sign-ups with other different areas of the brain so for example what you're going to find is moving down your brainstem you've got something called the reticular system okay or the reticular formation so this is the reticular formation and the reticular formation is there and it helps sleep-wake cycles so basically it's there to tell you whether you're awake or asleep okay it's this basically it's a system that when you're asleep it's suppressed and when you're awake it's activated and what's going to happen is that as this see fiber comes up it's going to send branches off and sign ups with the reticular system that means that when you have a C fiber activated stimulating the reticular system you end up being awake one of the reasons why you can't sleep when you're in pain because it's activated the reticular system another thing that activates as it comes up is the limbic system and so the limbic system is going to be involved in emotion so you're going to have signals coming off sent to the limbic system for example and the limbic system allows you to have some sort of a motive connection to it okay are you going to be happy are you going to cry you're gonna get depressed what is the association with it now a couple of other important points I want to talk about the fact that you can modulate pain at different levels so for example anytime you talk about modulating pain we're talking about changing pain changing the perception because pain is 100% at the level of perception now you may say that's not true because it's stimulated here sign-ups is here silent sign-ups is here silence is here so it's not just at a level of perception but it actually is because different to other types of sensory input for example you know that a particular wavelength of light will result in a particular perception in the brown color perception you know that a particular decibel will result in a particular sound perception in the brain but when it comes to pain you cannot adequately tell me that a certain stimulus here is going to result in somebody experiencing a certain type of pain you can't be sure the way I experience it it's going to be different to the way the next person experiences it I may say it's a 9 out of 10 the next person may say it's a 2 out of 10 and you've stimulated them the exact same way and the reason why is because pain is modulated or changed here peripherally here centrally here essentially or here essentially ok so how is it modulated all right well it's modulated a number of different ways firstly let's just talk about we haven't spoken about any of the neurotransmitters we haven't spoken about any of the other chemicals or anything like that so let's do that some of the chemicals that are released that stimulate pain and pain receptors include glutamate now glutamate is the main neurotransmitter for pain substance P and then there's other chemicals that can modulate pain and the weight modulates pain is often it reduces the threshold so if you've got certain chemicals released here or here for example what it can do is it can drop the threshold which means it makes it a lot easier to send a pain signal and these types of chemicals include potassium it includes bradykinin it includes prostaglandins many different other chemicals cytokines I mean I could probably list another 50 of them so many different chemicals now you may see that prostaglandins Brady cannons for example cytokines histamine these are all others tic tic these are associated with inflammation and this is important because there is a link between inflammation and pain and that's probably not a surprise to you because all inflammation is okay so inflammation is a response to injury to vascularized tissue so anytime vascularized tissue is damaged so this this is tissue with a blood supply you'll get an inflammatory response this means that a vascular tissue such as cartilage will not elicit an inflammatory response and is one of the reasons why it takes so long for cartilage to heal itself when it's damaged okay so these are all different chemicals so neurotransmitters for example and various chemicals that can modulate pain they can either stimulate pain receptors or they can reduce the threshold to make it easier to send pain so for example if here peripherally let's just say somebody cut my handle keep with the finger somebody cut my finger that's going to be damage to vascularized tissue and result in inflammation inflammation results in the release of histamine and Brady cannons and prostaglandins and what they do is they can stimulate pain receptors or or and they can drop the threshold and make it easier to send a painful stimulus and it goes in and the same thing happens here you also have the release of these chemicals centrally in the spinal cord okay which means it makes it easier to send the signal at the spinal cord level and going up and so forth now you've probably noticed that if you've fallen over or you see a little kid or you remember being a little kid falling over you rub the woman you knock your head you rub rub rub rub rub that to make it feel better how come rubbing some injured site makes you feel better this is something called the pain gate theory okay how does the pain gate theory work well what I'm gonna do is I'm gonna wipe this off for a second and I'm going to show you a more zoomed in picture of the spinal cord and tell you how the pain Gate theory is proposed to work now the pain gate theory has was proposed in the 40s and 50s and basically what it states pain gate the gate is there because it's says that you can basically gate off or limit a painful stimulus through other sorts of sensory stimulation so if you have the spinal cord so you have the spinal cord okay so you've got the spinal cord and what's going to happen is painful stimulus coming in dorsal root ganglion and that's the cell body of the pain neuron it's coming in synapse is here the second neuron which crosses over goes up not a surprise now touch signals coming in and remember I said the touch signal will jump into the dorsal column and go up the opposing side right what you'll find is that from this primary afferent sensory neuron that's going to the brain by the dorsal column you have some branches that come off at the dorsal gray horn and they will synapse with another neuron which is an in-between neuron called an inter neuron now I've even drawn up too small there so let's just draw it over here we've got the pain neuron sign-up sing with the next pain neuron which is going over and then going up and then we've got the sensory neuron coming in going up but you've got a branch that comes off sigh lapsing with what we call an inter neuron and as you can see this inter neuron synapses with the secondary nociceptive neuron the secondary pain fiber what's happening here is that when you get a painful stimulus positive positive pain touch well if you get a painful stimulus let's just say you knock your head right painful stimulus coming and going to the brain now let's just say you rub your head rub rub rub rub rub what you're doing is stimulating these blue fibers the fine touch fibers and as it comes in this branch synapse is with the inter neuron and sends a negative signal and inhibitory signal to the pain you're on and closes the gate on that pain signal so it can no longer get to the brain and so all that's getting to the brain is this constant touch signal that you're amplifying so basically the analogy that you can use since it's pain Gate theory is that there is a gate and there's only enough room for a certain amount of stimuli to go through if you bombard it with fine touch then the gate is closing on pain and pain when I get to the brain this is the proposed mechanism by which tens machines work so these are the electro stimulatory machines acupuncture massage therapy and other alternative therapies that seem to seem to modulate pain but again the evidence is limited to the use of a number of these types of alternative pain modulating therapies so that's the pain gate theory okay next thing I want to talk about is I even though I shall showed you that fine touch and pain go up to the brain via different pathways I didn't tell you about what the implications are of this the clinical implications I said I was going to tell you so let's have a look will be drawn up a lot of cross-sections of the spinal cord in this lecture spinal cord spinal cord medulla midbrain medulla pons midbrain medulla pons midbrain cerebellum thalmus okay touch you know it off by heart now it's coming in it's going up sign up seeing at the medulla crosses over goes up to the thalamus sign up says go to the part of brain dedicated to the hand let's do pain pain comes in sign up says at the dorsal great horn Decca sights at the level in which it came Xin comes in goes up the anterior lateral spinothalamic pathway sinuses of the Thelma's and then protects to the brain as well alright you see it's going up different sides what is the clinical implication of this now there is something called Brown Sicard syndrome Brown Sicard syndrome some people may be in a car accident for example and they may experience damage to the spinal cord but only one side of the spinal cord this is called a Hemi lesion which is damage on one side okay so let's just say somebody experienced the Hemi lesion on this side of the spinal cord what does that mean so let's just say this is the left side this is the right side let's say somebody experienced the Hemi lesion let's just say somewhere at the thoracic 5 level okay on the left-hand side what does that mean for touch coming from the right-hand side of the body so the lesion is on the left hand side what happens to touch that's coming from the right-hand side of the body below the level of the lesion so let's say touch to the foot or leg well let's have a look the touch is going to come in and to the spinal cord and go up the same side it came in which means the right-hand side and get to the brain unimpeded which means for touch below the level of injury on the contralateral side which is the opposing side you can still feel touch what about pain on the contralateral side well pains coming in from the foot goes into the dorsal gray Horn sign-ups as crosses over so deca sites at the level and tries to ace into the brain but it is impeded by this lesion which means you do not feel pain on the contralateral side below the level of injury what about a signal coming in from this side well let's have the let's have our spinal nerves touch is coming in goes up the same side impeded so touch on the EPSA lateral meaning the same side of the injury below the level of injury will not get to the brain and pain therefore sign APS's crosses over a sends unimpeded pain on the ipsilateral side the same side of the lesion but below the level of injury we'll get to the brain can you see these differences now so this is called brown Sicard syndrome and you can test these remember the pain pathway in the temperature pathway piggyback on one another so what you can do is if somebody's come in after a car accident for example and you want to determine whether that whether there is a spinal cord injury and at what level you can get an ice cube for example run it up the leg so you can start to a send-up particular limbs ice end up and ask them if they're feeling the temperature right so if they're feeling the temperature on this side on the right hand side of the body at the leg for example it means that the right hand side of the spinal cord has not necessarily been damaged right but if they if they can feel that pain but they can't feel touch then what it may mean is that there is a potentially on the same side of the spinal cord okay so that's called brown Sicard syndrome clinically very important all right let's move on so what I want to talk about now is how we can modulate pain through what we call the endogenous opioid system so you know that we produce our own analgesia so this is medications that can mitigate pain okay so let's just define some terms first actually so you've got lgz ER which is pain you've got analgesia which is no pain you've got a load in ER which is pain when they shouldn't be pain there is hyper lgz our hyperalgesia is increased response to pain and hyperalgesia which is decreased response to pain okay so allodynia is if I were to poke you now poking may be annoying but it's not painful but if it were to elicit pain and it shouldn't be right that's allodynia so when do you get allodynia you get a sunburn for example have you ever had a sunburn and then you've touched it and you go oh all that hurts and it shouldn't that's allodynia hyperalgesia is if I were to pinch you and it hurts a little bit but then the next day or to pinch you to the same degree using the same amount of force and you go oh my god that's so painful now well that's hyperalgesia you're experiencing even more pain so what I want to talk about is that our body has an endogenous that means coming from within analgesic system this is called the descending inhibitory pathway let's have a look at it so draw out more of that spinal cord let's just draw it coming up like this like this medulla pons midbrain and dollar pons midbrain cerebrum cerebrum fala my let's have the reticular formation which I said was you know stimulate stimulating you being awake and now let's send a pain signal in got a pain signal coming in sign apses deca sites asons thalamus cortex right now remember I said if it's a C fiber you're going to get all these afferents coming off and stimulating the reticular system but there's also something at the midbrain I'll just draw it like this and that's going to be called the periaqueductal gray Malins draw a bit differently okay this is called the peri aqueduct all gray matter which we sometimes just refer to as P a G okay periaqueductal gray matter next to the cerebral ventricles right peri aqueduct or near the aqueduct so cerebral aqueduct what do they do as the pain signal comes in obviously reticular system you're awake it also triggers the periaqueductal gray matter now the periaqueductal gray matter they control a descending pathway that comes down I'm going to draw the ascending pathway in purple so it sends signals down right now what are these signals do well these signals these descending signals the neurotransmitter so P AG the neurotransmitters that are used here are serotonin serotonin and nor adrenaline if you're American that's not epinephrine these are the neurotransmitters use for this descending pathway and what happens is when they get down to the spinal cord for example they release certain opioids opioids what are opieop ok opioids are these chemicals that are released that can reduce or mitigate pain for opioids they include endorphins I'm sure you've heard of that and endorphin release includes the in careful ins and includes the dine orphans endorphins and Kevin's done orphans what they do is they're released and they trigger opioid receptors and these receptors can be they called new receptors Delta receptors Kappa receptors right there's many different types of opioid receptors which are stimulated by these endorphins and careful ins and Dyne orphans then you're a transmitter that regulates their releases serotonin or adrenaline right and what they do is they will inhibit pain signals being sent they can do this peripherally so they can do this here opioids can act here peripherally they can act here essentially they can act up here in different areas right as well and they can act in the cortex so the opioids connect all throughout the system and what they do is they reduce the stimulus of pain being sent how do they do this well if you've got a painful stimulus it's going to release certain chemicals here and I said those chemicals are going to be glutamate it's going to be substance P prostaglandins you know a whole bunch of other stuff right and they need to be released and they need to bind to receptors here opioids stop that binding what they also do is they stop the release okay so they stop the release of the neurotransmitters for pain and they stop the binding of those neurotransmitters that may be available to the postsynaptic neuron this is how these opioids work now the opiates which are predominately exogenous compounds that mimic these endogenous opioids they include things like morphine and basically what they do is they mimic this activity which means morphine can act pro-pro peripherally and it can act centrally and again what it does is it stops the button the release of the neurotransmitters for pain and the binding and sending of the signal for the neurotransmitters of pain they can do this peripherally they can do it essentially okay now morphine obviously there's numerous side effects one of which is respiratory depression so what that means is if you give somebody morphine 'ok and reduce their respiratory rate how does it do this well we know that the midbrain the pons controls respiration so there's parts in the midbrain and pons here that control the respiratory process and they respond to increases in carbon dioxide right so they're sensitive to increases in co2 when you see our two increases it triggers these areas for example in the midbrain and you take a breath what morphine does is it makes these areas less sensitive to co2 which means they're not as a responsive to increases in co2 and therefore the respiratory rate can be depressed or respiration in itself can be depressed that's one of the things that morphine morphine also slows down the GI T for example so can result in constipation as well all right okay so what else what other types of drugs and medications can we use well the first thing we need to talk about as well before we move on to other types of meds is that you can have what's called acute pain and chronic pain now acute pain is pain that lasts less than three months so acute is simply a time frame right chronic is also time frame chronic pain is greater than three months this is usually right this is just an arbitrary value that we've been putting out but chronic doesn't mean bad acute doesn't mean good or vice versa there's simply time frames acute for pain is less than three months chronic for pain is greater than three months so what you'll find is that acute usually leads to chronic when it comes to pain how does this occur well if the acute goes unmanaged it can lead to chronic pain now acute pain is also often turned nociceptive pain while chronic pain is often termed neuropathic now there's exceptions to this but don't stress about that nociceptive pain is usually pain that occurs because some tissue has been damaged or is potentially being damaged and you're experiencing pain as a means to first recognize what's happening and hopefully try and avoid whatever action that you're performing so that that pain no longer occurs so that may be stop stabbing yourself with a pin or that may be stop touching the hot plate or it may be that you've cut yourself and that finger starts to hurt and it's telling you this finger hurts maybe don't use it for a while while I heal myself okay so if you do all these things then should within three months this acute nociceptive pain should diminish and disappear but what can happen is this pain different pain is different to the other types of sensory input such as sight smell touch sound and so so forth it's different in the sense that those stimuli you can become desensitized to so let's think of basic touch you wake up in the morning you put your socks on you feel your socks for about three to five second and then you forget about the feeling of the Sox for the rest of the day that's a desensitization you walk into a room you smell somebody's perfume after a couple of minutes you don't smell it anymore you're desensitized that's gone into the background same happens with sounds and visions and all those types of things pain is different when you experience a small amount of pain that system has evolved to amplify that pain pain doesn't so this is a good point because you should not just tough your way through pain if you experience pain you need to find a way to mitigate that pain okay now usually it's as simple as avoiding using the injured limb for example until the it's healed and disappears but if for example you don't let that heal you don't let the pain disappear what happens is it gets amplified and gets amplified at every single level here peripherally and here essentially how does it get amplified well a couple of different things happen first thing is I spoke about inflammation right so acute nociceptive pain is usually associated with inflammation so let's actually write that down so the acute nociceptive pain is associated with inflammation which means it's stimulated by those prostaglandins histamine Brady cannons for example and when they're released like I said they reduce the threshold of scent of pain neurons of nociception reduce threshold of pain signals okay so it makes it easier to send a pain signal now this can happen here in the spinal cord for example and what that means is all these chemicals so you get some sort of painful stimulus that sends it here and more chemicals are released here which means that this pain neuron the thresholds dropped and you don't even need to trigger this peripheral fiber very much at all to result in the same amount of pain and ultimately what can happen is no painful stimulus is being triggered here and you're still getting a painful stimulus here so you begin to get this hyperalgesia and then sometimes you can get this allodynia in which you're getting pain stimuli being sent through the spinal cord and there's actually no painful stimulus in the periphery that's sending it through now this is called central sensitization central sensitization and central sensitization results in decrease the threshold and you actually get the neurons changing a little bit okay in the sense that they increase the amount of pain receptors so you've got the threshold decreasing so easier to send a signal and more pain receptors which means it doesn't take much to stimulate them to send a signal either now this can happen and over time it becomes a chronic state right and because these neurons have changed so much that's what we turned in neuro Pathak pain which is usually changes of neurons or damage to neurons that result in chronic stimulation of pain receptors resulting in chronic pain now nociceptors pain was an indication that something's wrong and if you fix the underlying cause you fix the pain chronic pain there's no underlying cause triggering it so there's nothing you can do to mitigate it to stop that pain which means you've got to try and find the best way to not cope with that pain but try and reduce the painful stimulus some way or another so first of all if it's inflammatory nociceptive pain prostaglandin system in Braddock Islands what you can do is take certain types of drugs that are called NSAIDs now what NSAIDs will do so these are usually the first line of pain medication in short term short acute nociceptive inflammatory based pain NSAIDs include aspirin include ibuprofen includes celecoxib and people say yes people say no acetaminophen okay which is paracetamol so I'm gonna put it in and I'm gonna get people saying acetaminophen isn't an NSAID well I'm just gonna put it in anyway so aspirin ibuprofen celecoxib acetaminophen the NSAIDs now what they do is there are enzymes called Cox Cox 1 Cox - and they produce prostaglandins prostaglandins reduce the threshold of painful stimulus and sometimes can trigger a painful stimulus so they produce prostaglandins which means aspirin ibuprofen celecoxib Ceylon cinnamon ofin they block cox-1 or Cox - or both which means they block prostaglandins which means they reduce inflammatory based pain so when you have an inflammatory response prostaglandins are reduced causing pain you take NSAIDs stops prostaglandins stops pain ok this is what you can take in the acuteness receptive pain resulting from inflammation but what happens if it's moved on to a more chronic pain well NSAIDs don't necessarily work very well because it's no longer caused by inflammation so we need other types of pain relief medications so you can take the opioids for example which include the morphine's and the fentanyl's and so forth but again they don't necessarily have a great effect for chronic pain for many different reasons one of which is that even though the opiates can block pain transmission right centrally and peripheral it doesn't necessarily work that well and you don't want to use the long term that's the thing morphine for example because of their addictive properties morphine is usually used right for acute so short term intense pain or let's say severe pain so acute severe pain right there's an e on the end of severe acute severe pain it's up more things useful so that means what three to five days ish maybe right obviously variable it's not used for chronic pain because of its addictive properties and it doesn't necessarily work that well because of negative feedback because these mimic your own endogenous opioid system it negative feed there's a negative feedback system which tells them not to be released and therefore you have a negative homeostatic response so what medications can we then use for chronic pain well what we find now more and more so the types of medications that we are using now for chronic pain include the antidepressants and include the anticonvulsants so antiepileptic drugs and antidepressants a couple of different types of antidepressants that are used try cyclic antidepressants all right try cyclic cyclic I'm a horrible speller try cyclic antidepressants and also the serotonin specific reuptake inhibitors which are known as SSRIs yes honest or serotonin noradrenaline reuptake inhibitors which are called the S and eyes now these are all antidepressants that are used now remember here I said that for the descending opioid system that's coming from the P og periaqueductal gray matter also the racial nucleus as well which I the Rafe Magnum Magnus which I didn't talk about but there as well there's many different structures involved that the neurotransmitter involved for this descending inhibitory pathway for the endogenous opioid system was serotonin and noradrenaline which means that when they are released so think about there than your are transmitters which means when you've got a signal being sent right neurotransmitters need to cross that synapse so if you've got serotonin and noradrenaline let's write s and n they need to cross that gap and bind to serotonin and noradrenaline receptors on the postsynaptic neuron to send the rest of the signal now these serotonin specific reuptake inhibitors what does that mean well there are mechanisms that will take serotonin that's been released into the synapse and throw it back into the presynaptic neuron there are a uptake mechanisms that take noradrenaline throw it back which means that these reuptake mechanisms not these ones but reuptake mechanisms themselves recycle the neurotransmitters and they do not spend a very long period of time in this synapse very short period of time so if you inhibit this reuptake what are you doing you're keeping them in the synapse for a longer period of time increasing their likelihood to send an action potential by the second neuron right and increase in the release of the endogenous opiates which are the endorphins and Catharines and dine orphans all right so that's what the serotonin specific and serotonin noradrenaline reuptake inhibitors do they can also actually apart from inhibit the reuptake then they can actually block sodium channels on the postsynaptic neuron why is that important well we know when we need to send an action potential down a neuron that positive sodium ions need to jump into the neuron to depolarize it that's how all signals are sent right it's a depolarizing event positive sodium jumps into the cell that's all the signal is if you block that you block a signal right so that's another way of how they now they're not doing it on the neuron that's sending the endogenous opiate they do it at the pain signal so they block the sodium channels at the pain neuron okay so that's how these SSRIs SNRIs work the tri cyclic antidepressants or the trus cyclic antidepressants they also play around with serotonin noradrenaline as well and they can also block sodium channels and they can also block calcium channels too so they block serotonin reuptake noradrenaline reuptake they can block sodium channels and it can block calcium channels why calcium channels well calcium channels we know that once an action potentials reach the end of a neuron calcium needs to enter at the end of the neuron because calcium is the trigger to release neurotransmitters so if you block calcium voltage-gated calcium channels at the pain neurons you're blocking the release of neurotransmitters associated with sending a pain signal okay so that's again one of the ways of this tricyclic antidepressants work so they're the antidepressants you've also got the anticonvulsants and probably the only one I'll talk about is gabapentin and gabapentin works that exact same way calcium channel blocker it's a calcium channel blocker which again means it's blocking calcium entering which inhibits the release of the neurotransmitters for pain okay so these seem to be the most prominent pain meds for chronic pain so what are the types of pain meds you can have you can have non-steroidal anti-inflammatory drugs they're there NSAIDs so that's the aspirin that ibuprofen the celecoxib this freedom in ofin they block the prostaglandins and blocking inflammatory pain that happens both peripherally and essentially you can then have the opioids so this includes morphine and fentanyl and they mimic the endogenous opiates system of endorphins and Kev ones and endorphin endorphins and Kev lens and diamond orphans and what they do is they block pain transmission and they can also alter what's happening up here in the brain essentially alter the perception of brain is perception of pain too but that's more difficult to discuss and then for chronic pain you can have the antidepressants which predominantly work by inhibiting the reuptake of serotonin or adrenaline and also the anticonvulsants like gabapentin which block calcium channel voltage-gated calcium channels which stop the pain receptors releasing the pain neurotransmitters such as substance P and glutamate for example so we've gone through a lot here with pain there's obviously a lot more that we could talk about but maybe I'll just finish it here if you have any questions please feel free to send it through but that is a quick run-through of pain pain pathways analgesics NSAIDs opioids and chronic pain relief medications thanks