Neuro: 2-3 Pm Scribe: Lital Silverman

Neuro: 2-3 pm Scribe: Lital Silverman Wednesday, Feb 3 Proof: Name Here Dr. Lester Pain!!! Page 1 of 7 I. Introduction PAIN!!! [S1]: a. So, pain. First of all I’ll need a couple of volunteers. Now I know who all the masochists are, right! (Laughter) Now, Dr Gamler’s going to need some volunteers later on so we’ll save volunteers for him. b. So I’m going to try and quickly compare and contrast the pain, and somewhat, the temperature pathway with the fine touch proprioception pathway that Dr Weller just talked about. Obviously there’s some overlap and there are some differences. Pain is separate obviously because it’s one of those senses is clinically more to the forefront: most people go to their clinicians, physicians, doctors, optometrists, and dentists when they are suffering from pain right? That’s why you go to the doctor the most, so, we’ll keep it a little bit separate. II. Pain… [S2] a. So, like fine touch and vibration and proprioception, pain is a modality of somatosensation. It’s the perception, real or theoretical – so you don’t actually have to have any damage or anything, you can just perceive that you have it – unpleasant or aversive sensory or emotional experience. (Emotion back in here). b. So physiologically it’s going to warn you if you’ve gotten any injury or you’re likely to get an injury, ok? So it’s an important sense and we know that people who suffer from a lack of pain perception can get into very serious trouble, right, you can lose an arm or a leg pretty easily without knowing about it. It’s highly individual and subjective: we can alter our pain thresholds quite substantially, and that’s probably – as I’ll talk about at the end – because we have some control over our endogenous pain chemicals. III. General Topics [S3] a. Don’t worry about this; it’s just a list of key things of key things that you should know by the time we’ve finished. IV. Clicker question a. Question: what tract carries pain information? 1. corticospinal, 2. spinothalamic, 3. dorsal columns, 4. medial lemniscus, 5. trigeminal thalamic b. answer: 2. Spinothalamic c. So you should know this my now, and you should also be getting the impression that although we’ve covered sensory pathways in the first part of the course they’ve cropped up again in this part of the course and therefore may again appear on the exam. So you still need to know where they run, and where they cross in the central nervous system. d. Spinothalamic, pretty good. Corticospinal being motor. Dr Weller just talked about dorsal columns and medial lemniscus, and you should keep those together, right? Dorsal columns, once they get up into the medulla and cross form the medial lemniscus. e. Trigeminal thalamic, well, this also carries pain, right? It carries all sensory modalities from the head including pain and temperature. One part of it, one nucleus of the trigeminal nucleus, the spinal nucleus of five is the one that carries pain and temperature. Then the main sensory nucleus is the one that is going to carry fine touch and vibration. And then you’ve got another one, the mesencephalic which is going to carry propioceptive information from the jaw. V. Learning Objective #1 [S4] VI. Dual ascending sensory pathways [S5] a. This is just a diagram to compare and contrast the two main sensory pathways, so we have them clear again. It should just be review, right: dorsal column, medial lemniscus. So we can see that in green here, look we’re coming from some sort of sensory nerve ending, encapsulated, comes into the dorsal column, doesn’t cross over, ascends ipsilaterally into the medulla, crosses over, forms the medial lemniscus, and goes up into the VPL of the thalamus. b. Contrasting with the anterolateral pain and temperature pathway which enters via the substania gelatinosa or the dorsal horn; synapses somewhere in there, usually, crosses over, and ascends in the anterolateral system. So it’s contra-lateral, but again goes up to the VPL. c. We call this the anterolateral system because as we can see, it doesn’t just carry the spinal thalamic tract: the spinothalamic tract is a major component of the anterolateral system but there are other pathways. But, I don’t mind too much, if we kind of use those terms interchangeably, I’ll know what you mean, so we won’t penalize anybody too much. VII. Pain and Temperature [S6] a. This is just a little more detail showing entry of the afferents, the sensory afferents, into Lissauer’s tract, where you remember they ascend and descend a couple of segments before they go in and cross over. So we can actually get damage higher up that where we lose sensation. You can see that they can form multiple synapses, so either in the marginal or the substania gelatinosa layers, layers one and two. Obviously a lot of these cross over, but some of them will send branches or make synapses with neurons that go into the ventral horn, and they are then going to synapse on alpha motor neurons, because important reflexes, as Dr Gamler Neuro: 2-3 pm Scribe: Lital Silverman Wednesday, Feb 3 Proof: Name Here Dr. Lester Pain!!! Page 2 of 7 will talk to about, if you’re walking along a beach and you tread on a piece of glass that requires a reflex for you to withdraw your foot: you’re withdrawing it from pain. b. So there needs to be some kind of reflex pathway connecting pain to withdrawal. So probably involving interneurons in that case. c. This also points out that, although I don’t want you to remember all the different peptides, but one associated with pain a lo,t especially in the C5 afferents, these unmyelinated afferents, is Substance P. So this is just stating for substance P in the superficial layers of the dorsal horn; so, substance P remember with pain. d. We’re also going to talk about enkephalins, and endorphins, so we do have a group of peptides that are kind of pain related that we should know about. VIII. Teaching Objective #2 [S7] a. Ok so we’re going to talk a little bit here about velocities of pain fibers. Because I know everybody here doesn’t have the book, what I’ll do here when I get back is there’s a nice little table in the book which compares all the different types of fibers and their velocities and what information they carry. Because there are multiple naming systems for those, it shows which ones go with which. We talk about C fibers, then we talk about 1-alpha or 2 alpha fibers and which ones correspond so it’s a nice little table. I’ll show you that in a minute IX. C fibers use two transmitters: substance P and glutamate [S8] a. So again here’s a synapse in the spinal cord between an incoming C fiber onto a dendrite, right, and what you can see are there are little clear vesicles lined up and they are going to store glutamate--and that’s going to be our fast synaptic transmission, the transmitter between our sensory afferents and the spinal cord, and that we know is likely to be true for all of our sensory information coming into the spinal cord. b. You can see these dense core vesicles somewhat scattered around in this pre-synaptic terminal and they’re the ones that contain substance P, and they, remember, are going to be released more so with stronger stimulation. c. So for example, if the pain is acute and not very strong the signal might only need glutamate to signal to the spinal cord and up to the brain. But if we have persistent pain, it carries on for a long time; we get lots of action potentials coming down into this terminal: now we’re going to start to release substance P, and substance P is going to exaggerate synaptic transmission here. It actually acts to affect synaptic transmission through glutamate receptors, and we’ll talk about that again when we talk about sensitization. d. Remember, Dr Weller, when she talked about touch receptors, most of those receptors kind of desensitize so they’re active more at the beginning and then they fade away. The idea is that you get dressed in the morning. And you put your clothes on, and you kind of feel it, but you don’t wander around all day with the sensation that your clothes are brushing against you, you get desensitized to that kind of vibratory pain, or vibratory touch X. Afferent termination in dorsal horn [S9] a. You’ll find lots of different diagrams for showing inputs into the different layers from the different fibers. I’m not going to worry about this too much, ok, this is just to show you that C fibers and the A delta fibers, which are the ones that we’re more interested in for pain and temperature, tend to synapse in layers one and two, the marginal and the substantia gelatinosa. b. But there are some synapses with deeper neurons which would then carry information either across contralaterally or into the ventral horn where they might activate motor reflexes. XI. Question: What type of information is conducted the fastest? a. Dull pain, proprioception, touch, sharp pain. Answer: proprioception. b. Remember, I think I set this right at the beginning of class: probably the most important thing for humans is being able to move really quickly when you want to move, right? So your alpha motor fibers are very fast signaling. But of your sensory modalities, in order for you to be able to move accurately and to know where your joints are in space and your muscles and what they’re doing, you need reliable propioceptive information. Because otherwise we would not have any baseballs players or basketball players or anything like that because they’d be completely uncoordinated, they wouldn’t be able to catch balls or hit balls or whatever, right? So we need to know where our body is in space so we can constantly adjust it without thinking about it. c. So proprioception is our fastest sense, and when I send you the table, you’ll see this listed, ok? d. Followed by touch at least in this scheme of things, and then sharp pain which tends to be carried by A delta fibers and dull pain which is carried by our unmylenated C fibers. XII. Conduction velocities[S10] a. And that’s shown here, simply, up here we have A alpha and A beta, so we’re representing basically, A alpha, right, alpha muscle, alpha motor neurons, propioceptive information would be in this speed. So this represents conduction time, so things get fast. b. A delta, slow, which has sharp pains but also carries some temperature information – is going to be a little slower – Neuro: 2-3 pm Scribe: Lital Silverman Wednesday, Feb 3 Proof: Name Here Dr. Lester Pain!!! Page 3 of 7 c. but you can see C fibers are going to be really slow. They’re unmyelinated, very thin fibers; it takes a long time for information to travel up through C fibers. d. The problem is, once you start C fibers going, and they get turned on, you’ll see they’re pretty hard to turn off, so you can have this dull aching pain for long time. And, unfortunately, we couldn’t have Dr Ness follow up with a clinical lecture straight after me, so you’re going to get him in a couple of weeks, but he’s going to talk about the clinical implications of these dull, neuropathic pains and how hard they are to treat. XIII.Noticeptors are free nerve endings[S11] a. And this is just a simple diagram showing you, well, if you cut the myelinated A delta you lose the fast pain – the sharp pain – and if you cut the C fibers you lose the slow pain, you should know that. b. So this is similar to the diagram that Dr Weller showed you right, here are all our sensory nerve endings. The only thing that we’re going to worry about for pain and temperature is that pain and temperature don’t have encapsulated endings, they have free nerve endings. So pain and temperature are just parts of the axon which just forms nets and just sit under the skin. c. And in those free nerve endings are going to be lots of things, lots of receptors. There are going to be mechano- receptors, there are going to be receptors for chemicals, and one other type of receptor, polymodal thermal receptors, so extreme temperatures. XIV. Teaching Objective #3 [S12] a. Ok, so we call the free nerve endings nociceptors, that’s the term. It’s not the term for the individual receptors that sit in the membrane, it’s the terms for free nerve ending: that’s the nociceptor, right? So that’s equivalent to the photoreceptor or the hair cell. Nociceptors are the receptor mechanism for pain. XV. Nociceptors [S13] a. So the membrane of these, contain the receptors. b. And we get them in the face, the trigeminal ganglia neurons have free nerve endings, that where we get pain from our head, as well as the dorsal root ganglia carrying pain from the body. These are the classes, and we’ll talk about them a little bit, ok c. Thermal: a delta and c fibers carry normal temperature, temperature we would think was normal, you know when you put your hand in there it feels warm or cold, but you don’t have to remove your hand. But they also carry thermal receptors which are extreme receptors, that are burning either hot or cold. d. Mechanical: I’ll show you an example of this. Again, you can think of these as being an extreme version of the touch receptors, these are receptors that require extreme mechanical pressure to respond. So you have to jab yourself, or really deform your skin to feel pain. e. And then these polymodal ones, these are the really nasty ones because these are the ones that spread the pain out and amplify the pain and release all sorts of chemicals and just keep the whole pain thing going for a long time. You get sun burnt, that’s what’s going on. XVI. Chemical nociceptors [S14] a. So this is just a few things, I just tried to list a couple things that might be going on with our chemical nociceptors. So remember dorsal horn of the spinal cord these pseudo unipolar neurons, dorsal root ganglia and they carry information generally from the periphery into the spinal cord. b. But this is a clear example here of where you can see that they are releasing things as both ends: there’s a release of chemicals both out in the periphery and centrally. c. So, first of all, when we’re damaged, we release chemicals from the tissue that is damaged. Platelets, endothelial cells. One of the easiest things that you’d think is released is potassium: you release a bunch of potassium, guess what, you depolarize a bunch of nerve endings. Action potentials, you’re already signaling pain just by releasing a bunch of potassium. You can release other things: histamine from mass cells. Serotonin gets released, bradykinin another peptide which is released. d. All of these act to sensitize the nerve endings to other chemicals, so now these nerve endings are much more sensitive, and anything will set them off. When we increase sensitization or increase painful stim-- or change the threshold of painful stimulation we call that hyperalgesia. It was a little bit painful before but now when we touch that area it’s really painful. e. A few other things happen, which is really cool, so instead of this information going straight back to the spinal cord to say pain is coming, it goes down collateral branches. The pain not only stays where it happened, it starts to spread to adjacent areas. You can release things there, substance P, which we know is released in the spinal cord, calcitonin gene related peptide is another thing which again tends to activate mass cells to release histamine. f. They also affect blood vessels and cause vasodilation, so we’ve got inflammation going on, and cause extrovasation, so leakage of fluids from the blood vessels which causes swelling of the area and sensitizes and tenderizes it. Neuro: 2-3 pm Scribe: Lital Silverman Wednesday, Feb 3 Proof: Name Here Dr. Lester Pain!!! Page 4 of 7 g. We release arachidonic acid from membranes: arachidonic acid makes prostaglandins and prostaglandins are also part of this whole sensitization process. Remember that’s where these Cox inhibitors, like aspirin, act on cyclooxegenases to actually decrease the production of things like prostaglandins. h. So there’s lots of things going on with these free nerve endings, but just remember these general patterns that there are chemicals released, there are local and central effects, and pain can spread and be amplified. XVII. Thermal nociceptors [S15] a. What I’ve shown you here are normal thermal receptors. Here’s a cold receptor, it’s gonna respond when the temperature is around 25 degrees or less. Here’s a warm receptor, it’s starting to get warm, 40 degrees, but you can put your finger in 40 degree water you’re going to be ok. b. Thermo nociceptors are activated by temperatures outside this range, extremely cold or extremely hot. What’s become known recently is that these receptors are part of these transient receptor potential class, these TRP channels. Again, remember like I said for taste, like we associate spicy food with hotness, there’s kind of a pain going on there: same thing here. So extreme temperature using these trip channels which may be activated by other things: you get some hot chilli pepper on your finger, it starts to burn, it’s probably activating these TRP channels. c. Pain, temperature, spinothalamic tract – these are both going together. d. Again, to mention that just like those chemical responsive free nerve endings the pain and temperature ones are also free nerve endings. XVIII. Mechanical nociceptors [S16] a. Here’s the mechanosensitivity, this is where we could have a volunteer… You can see here we’re not testing for touch, we’re testing for pain. So, one assume we’re recording from a pain fiber, here is an afferent fiber. b. The first experiment, in A, is we just touch the finger. If you touch your own finger, you can feel that, it’s not painful but you feel it, it’s touch – that’s your dorsal column system. And you can see quite a bit of force, you can push down there quite a bit, deep, you can feel that, it’s still not painful: no response from the afferent fiber. c. Now we take a pin and stick it in you, it’s not really that painful. I’m not really jabbing it in you, I’m just going to depress the skin a little, not too bad, right? But it starts to set off firing in our pain fiber-- d. And here’s a nasty one, where I get a pair of forceps and squeeze a bunch of skin together. A big squeeze, lots of pain, lots of signaling. Again telling you a general phenomena about how the brain utilizes action potentials: the stronger the pain, the more the action potentials. We’re using frequency coding to signal intensity of pain, just like we do in other sensory modalities. XIX. Sensitization of nociceptors [17] a. This is an example of hyperalgesia (that another Dr Ness is going to talk more about). So here’s our area of skin [pushes own finger onto hand], I push on it till it’s painful, it takes me so much I can take a lot, because I have a good threshold for that. But if I burn myself, I’ve got some damage here, and if I push on that, the threshold’s changed, becomes a lot more painful to mechanical stimulation: that’s mechanical hyperalgesia. b. The area of the initial damage has spread, so that’s this idea that this information is coming into the CNS but going down the collaterals, and then activating areas adjacent. XX. Pain pathways sensitize!!! [18] a. So, here’s two terms we can define: hyperalgesia, and allodynia. And they’re kind of similar; we’ll make a distinction between them. b. So, the hyperalgesia it’s really the threshold decreases, right? And magnitude of pain from superthreshold stimuli increases, so things that were only mildly painful before now become extremely painful. Hyperalgesia. c. Allodynia is different. Things that were non noxious before, like touching or rubbing your skin, now become incredibly painful. So we’ve actually transferred modalities, we’ve transferred touch into pain. d. A big thing to remember is that pain pathways sensitize, they don’t desensitize. At the site of injury, there’s an increase in the pain over time. With severe or persistent injury, there’s a type of plasticity that happens. And the reason this happens is that those C fibers are continually getting exposed to chemicals and stimulated and they don’t get desensitized, they carry on firing action potentials, and those action potentials, then, when they reach the spinal cord, cause plasticity. They actually change the efficiency of those synapses so that pain information is carried into the central nervous system even more efficiently. It’s been termed wind up. A plasticity that involves a glutamate receptor called an NMDA receptor, and later on in the course we’re gonna talk about central brain plasticity involving NMDA receptors, and it’s actually pretty similar. A plasticity that exaggerates the pain. So not only does the pain get strong because it’s repetitively activated, it actually changes the synapses after a while. e. Dr. Ness will talk about neuropathic pain, pain that cannot be directly traced to the site of injury, or persists, or is totally out of proportion to the damage. So after the pain has subsided the injury has healed up the person still feels a lot of pain. Well, it probably involves central mechanisms like this that have changed the encoding of Neuro: 2-3 pm Scribe: Lital Silverman Wednesday, Feb 3 Proof: Name Here Dr. Lester Pain!!! Page 5 of 7 pain somehow, and it’s very difficult to treat. And it’s what most people that have lasting pain syndromes suffer from. XXI. Teaching objective #1 [19] a. Ok, we’ll quickly do some anatomy. XXII. Spinothalamic [20] a. And most of this we’ve done before. So I’ll try to point out some differences. b. We know spinothalamic right, comes in, synapses, crosses, goes up in the anterolateral system, to the VPL. The body pain goes to the VPL part of the thalamus. And then up to the cortex, anterior, posterior, lateral. c. You can see, though, the pain fibers go to other parts of the thalamus, Dr. Weller mentioned this. I’m not going to worry that we know all the parts of the thalamus that pain goes to. We definitely need to know that it goes to the VPL, there’s talk about it going to the VPI, the intralaminar nuclei, just know it goes to other parts of the thalamus, and then it can be distributed more diffusely to other parts of the cortex. XXIII. No title [S21] a. This is another example comparing and contrasting the dorsal column medial lemniscus, and the pain fibers. showing you pain fibers going to the intralaminar nuclei of the thalamic nuclei, contrasting with the dorsal column medial lemniscus, going just to the posteriolateral complex. b. XXIV. Pain pathways through thalamus [22] a. And this divides up pain perception in two ways, the VPL VPM, VPL body, VPM from the face, coming from trigeminal thalamic tract. Is basically gonna tell you where the pain is on your body. Location of pain is coming to the VPM and the VPL. And that makes sense. Dr Wallace showed you the mammunculous, the topographic map, so as well as touch being mapped on there, we can map pain on to there. So that’s a nice topographical arrangement, probably go on to postcentral central gyrus, to those primary sensory areas. b. But from other areas of the thalamus, we might go to other places, and we might receive projections that we’ll talk about in a minute. And these might go more diffusely, they might go to more visceral parts of the cortex, more limbic parts of the cortex; remember, pain has a lot of limbic associations with it, so it wants to go spread out and interact with other parts of the cortex. XXV. Teaching Objection # 4 [23] XXVI. Ascending pain pathways [24] a. Ok these are the two other pathways that you need to know. b. Spinoreticular, so it’s coming from spine to reticular formation of the brainstem, which is largely in the medulla and the pons. c. Spinomesencephalic, meaning spinal pathway to midbrain, this is the one Dr Benos talked about that is gonna that is gonna interact with periaqueductal gray in the midbrain, and is involved in pain modulation. XXVII. Spinoreticular [25] a. Here’s spinoreticular, kinda makes little side trips into the reticular formation of the medulla and the pons— b. As Dr Benos mentioned, that reticular formation is part of ARAS, ascending reticular activating system, it kinda feeds into this idea that he told you that if you’re unconscious, and you want to be woken up, nice little bit of painful stimulation might be the way to do it. Well there’s the pain pathway that’s feeding into the reticular formation that might arouse you if you’re at least at a certain level of consciousness. c. Again you can see it does follow up to the thalamus, and up to the postcentral gyrus, so it is carrying pain information, it’s just doing a few other things on the way. XXVIII. Spinomesencephalic [26] a. Ok so here’s our mesencephalic pathway, and here is our periaqueductal gray around the central canal. b. And this has a big role in the descending control of pain. c. We’re gonna talk about, in a minute, the two ways in which pain is gated. Pain is highly regulated, it’s regulated in a descending manner, through the periaqueductal gray; it’s also regulated, or gated, as it’s ascending. And we want to understand those two mechanisms. XXIX. Teaching objective #5 [27] XXX. Descending control [28] a. So here’s our descending control, I’ve got a couple of diagrams, don’t worry about all the details. b. It’s been shown, if you go in and directly stimulate, electrically, the periaqueductal grey, around the canal, you can actually change somebody’s pain thresholds. Takes a lot more pain for them to feel painful stimuli. So there’s something about the periaqueductal grey (and what it does and what it contacts) that gates pain. c. We know that the periaqueductal gray contains a lot of natural enkephalins and endorphins, so it contains a lot of anti noxious chemicals. It also contacts a lot of other things on the way down. Neuro: 2-3 pm Scribe: Lital Silverman Wednesday, Feb 3 Proof: Name Here Dr. Lester Pain!!! Page 6 of 7 d. In particular, it contacts the Raphe nuclei. Now the Raphe nuclei—what chemical? Serotonin—so this is a serotonin descending regulation of pain, plays a big role, serotonin down to the spinal cord. XXXI. Other transmitters [29] a. This kinda puts a bunch of it together. And actually involves a couple of classic chemicals: noradrenalin and serotonin. b. So we have our periaqueductal grey descending down to midline Raphe nuclei, which are serotonin, down to the dorsal horn, nice convenient spot because that’s where our pain fibers are arriving in. c. But, there’s also descending control from the locus ceruleus, so we’ve got norepinephrine fibers, and there’s also a lot of natural opioids in the locus ceruleus that come down. d. In the spinal cord itself, you have a lot of interneurons that contain opioid chemicals, enkephalins. The basic idea would be for this descending control to synapse onto these local interneurons and perhaps release some natural anti-pain chemicals, the enkephalins. XXXII. Local circuit interneurons… [30] a. And that’s indeed what’s thought to happen. b. So at the most cellular level, here’s our dorsal root ganglia, here’s our pain fiber, coming in. It’s releasing substance P and glutamate onto our neuron in the substantia gelatinosa, or wherever it is in the dorsal horn. So we’ve got pain transmission coming through there. c. Now, we get a nice EPSP or action potential in our projection neuron so our pain is transmitted up through the spinal cord, up into the cortex. d. So couple of things to mention here, here’s where pain control has been used a lot clinically by using compounds like morphine, because there are a lot of morphine/new opioids receptors on these pain fibers, so we can exogenously target morphine to actually decrease stimulation through this pathway, because morphine tends to hyperpolarize neurons. Or tends to inhibit calcium entry into presynaptic terminals. So it cam kinda helps stop pain remission though by using morphine as an exogenous drug. e. But, we’ve also got an endogenous mechanism. These enkephalin-containing interneurons of the spinal cord. If these things get activated by descending serotonin or norepinephrine fibers, will flood that area with enkephalins, which will do the same thing as morphine. And it will tend to reduce the signal from the C fiber to the spinal cord fiber, and therefore gate or control the amount of pain that gets through. f. People get confused, (and I write bad questions on the subject), this is the descending control of pain. Coming down from periaqueductal grey, and serotonin and epinephrine releasing endorphins, it’s descending control. It’s gonna contrast with what I’ll tell you about in a minute g. This is an interesting phenomena. This is probably how most of us are able to regulate our own pain thresholds. i. And there was a famous experiment that was done, where they put a little device on the subjects’ wrist, it caused pain, turn up the dial, the subject would say stop, that’s too painful. And then they gave the subject a drug, they said it is an analgesic, it will take away some of the pain. Did the same experiment again. Turned up the pain… This time they noticed they could turn up his pain thresholds right up, they were able to turn it up more and more and he didn’t feel it till it got to a much higher level. ii. Well turns out they gave him a placebo. There was nothing in that drug. But to show that there was actually a physiological basis for it, they did another trial and they gave him another drug, Naloxone. And Naloxoneblocks enkephalin action. And when they gave him Naloxone, he wasn’t ale to keep his pain thresholds elevated. Because what had happened is that the placebo had convinced him that he was getting a drug and he’d released a whole bunch of enkephalins, gave himself up “oh, I’m not gonna feel that pain”, did it naturally. But the Naloxoneactually blocked that, so once it was blocked he felt the pain. So there’s a placebo, and there’s a big difference in personal experience in how we feel pain. XXXIII. Teaching Objective #6 [S31] XXXIV. Gating control hypothesis of pain [S32] a. Ok, now, this is gating ascending pain. So we’ve done the descending, this is ascending. It’s kinda cool, and there’s an easy way of remembering it. It’s something we all do, when we experience pain. So, let’s imagine hitting our hand hard on the bench. What is the next thing you do? Shake it out, or rub it. Why would you do that? I mean, you do it automatically. I have no idea if it has anything to do with this type of gating. But maybe it does. b. So here’s our pain fiber coming into the spinal cord, big activation, just whacked my hand, lots of pain, strong activation. Turns out there’s an interaction in the dorsal horn between the noxious, the C fibers and non- noxious, sensory fibers, coming in, so vibration from rubbing and proprioception from shaking, those are coming in as well, and they send out collaterals that turn on inhibitory interneurons. So guess what, when those fibers are activated, there’s inhibitory interneurons stimulated, which tends to decrease the amount of pain that’s coming through that C fiber up through the spinal cord. So it makes sense. Neuro: 2-3 pm Scribe: Lital Silverman Wednesday, Feb 3 Proof: Name Here Dr. Lester Pain!!! Page 7 of 7 c. So if you remember that, bang your hand, rub it, that’s vibration, shake it out, that’s proprioception, you’re increasing the activity of non noxious fibers going into your spinal cord, and it works! It definitely decreases your perception of pain when you do that. So there is a physiological basis, we think, for that. XXXV. Cortical representation of pain [S33] a. So that was descending control and ascending control, ascending control is sometimes called gating the pain. b. This is just to kinda complete the story because we talked about pain being a little more diffuse. We have our main thalamic nuclei going to primary somatosensory. We’re aware of the pain conscious level, location, and maybe in part intensity of the pain. Because we’re going to have the number of action potentials come up there tell us about intensity. c. It also projects to insular cortex and cingular. Insular we tend to think about autonomic and visceral components. And cingular we know is limbic, memory, Hape’s loop, which well talk about more. So maybe there’s some memory type things about pain, or more emotional aspects of paint that we remember. But just to let you know that pain is more diffuse. And it could go to these other regions, it probably goes into other cortical regions as well. XXXVI. Referred pain [S34] a. And then there’s one final thing, which is sometimes important, definitely in non-western medicine, which is referred pain. b. When you feel strong pain in your left arm, what does that mean? Heart attack. c. The main idea here is that dermatomes and viscera, are internal organs, tend to synapse together at different layers of spinal cord. And receptors here tend to be more silent and to the ones on your dermatome dominate, functionally, but occasionally the visceral pain receptors are gonna dominate, but your not gonna be able to tell whether that pain came from the viscera or from the corresponding dermatomes. And that’s why different pain from different visceral organs may be associated with pain from different parts of the body. That’s referred to as referred pain, and can actually be a useful diagnostic tool XXXVII.Question: a. Which area should be excluded? dorsal horn, STT, periaqueductal gray, Raphe nuclei, substantia niagra, locus coeruleus b. Answer: substantia niagra. c. A clue: what have we been trying to be talk about the last hour? Something that I did not mention one of those things there. But by the end of next week you’ll be sick of that nucleus. Pretty good! Substantia niagra.