descending monoaminergic analgesic pathway for this i think i can tell you a story what is that that we have heard that you know many times when we are hearing that those soldiers who are at the border areas they had bullet injuries of one two or three of that but still they continued to fight the now the question is or maybe a sports person who is participating in the olympics and he ha he is about to reach his finish line and he suddenly gets a sprain on his leg but he doesn't stop there he or she doesn't stop there what does he do he continues to keep running the soldier continues to keep fighting the sports person continues to keep running and going for the finish line what exactly has happened at that time is that the pain was not there at all what had happened that they did not feel the pain at all and they continued to keep uh you know their activity and the answer to that is because there is an endogenous in her you know inside our body endogenous descending monoaminergic analgesic pathway since the neurotransmitter released here is your serotonin nor adrenaline so they are monoamines we call this as descending descending means it is coming from the highest center to my spinal cord since this fibers are descending we call them as descending and we call them monominergic because they are involving monoamine neurotransmitters hence the pathway is called as descending monoaminergic analgesic pathway so what has happened we have seen this is the circuit isn't it this was my projection neuron and we have the nausea septals who go and stimulate these projection neurons isn't it and they are going to stimulate and so we are going to get the pain perception what has happened to the uh here we will talk about it here itself now actually this is what is happening this is one so we'll go one by one what is the center for this this is the higher center it is coming from you know lot of emotions are involved here so we have lot of emotions coming you know we have lot of impulses coming from the higher centers they go to an area called as periaqueductal grey area of midbrain so they come and converge over this nuclei that is periaqueductal gray matter in the midbrain and what is these fibers are actually these fibers they once they get stimulated they start sending the impulses okay so they come they give the impulses and they kind of stimulate their descending pathways which why are the locus cellulose you know they go and innervate to the local cellulose of pons they also go and stimulate the nucleus raphe so the raphe nucleus and raphael nucleus we have seen when we were talking about the neurotransmitters that they are going to release the serotonin serotonin is 5-hydroxytryptamine so they are very rich with serotonin so we have the stimulation of the raphe nucleus from the periaqueductally gray areas so periaqueductal gray area so let me start with the pathway periaqueductal gray area they go to now they start from where they are starting from the midbrain then they go to ponds in the ponds they stimulate locus cellulose so locus cerulus in turn is going to give the nor adrenergic so locus cerulus is going to release the non-adrenergic norad nor adrenergic pathway okay so which is ultimately going to my spinal cord that is one thing that this will do other thing is that the fibers which had started from periaqueductal gray area they give fibers to locus cellulose as well as they go to raphael nucleus now from our previous knowledge of neurotransmitters we know that raphael nucleus is the rich neurons you know they're having the cell bodies which are literally in you know for the release of serotonin so they're going to release the serotonin and so these we have the serotonergic fibers which are going to the spinal cord so actually we have the two pathways which is descending two monomer check pathways which is descending on to my spinal cord one is from the raphe nucleus that is the serotonergic nerve pathway and from the locus syrus we have the nor adrenergic pathway okay so what happens now so there is you know a lot of emotions lot of stuff which is involved from the higher center the higher centers are stimulating my periaqueductal gray area matter nuclei they in turn is going to go and stimulate two nucleus one in the pons that is locus cellulose other in medulla that is nucleus graphene magnus locus sterlus is going to stimulate the non-energy nor adrenergic pathway hence this pathway is going to be stimulated and the fibers which are coming to the raphe nucleus they are going to release the serotonin and the serotonin is going to converge into the spinal cord now what happens at the spinal cord level so let us see this diagram i think this is going to tell us a lot so we have two fibers you know coming down descending down one is from the locus sterilis bringing the norepinephrine and one is from the raphael nucleus that is certain well good enough what will they do serotonin is going to cause you know these these twos say norepinephrine and serotonin they are going to stimulate the encephalin neuro interneuron in kaphalin interneuron is actually an inhibitory interneuron this is a inhibitory interneuron so what will this inhibitory interneuron will do they will stimulate the inhibitory interneuron and these inhibitory interneuron in turn is going to inhibit ah now as we have seen in the gate control theory they are going to inhibit the perception you can say the you know transmission of pain via the projection neurons okay so let us see one more diagram for us to understand how it is so this is how the local interneuron this is one picture which is going to tell in detail for us that we have sensory inputs alone and what if we have the opioids encephalins so it is interneurons are actually encephalin energy interneurons and so they are going to release the encephalin and caffeine is your endogenous opioid which is going to stimulate the receptors the morphine receptors and so the pain perception is going to be reduced okay so let us take a condition where there is sensory input alone so we have the nociceptor sensory neuron we have stimulated it once we stimulate it it is going to release as i told you right glutamate it is going to release the glutamate and glutamate is going to cause the you know the whole of the mechanism that is they are going to release uh the the neurotransmitters are going to go and bind to their amta ampa receptors and nd nmda receptors who in turn is going to cause the influx of the calcium ions and the sodium ions and all that so what is it happening since uh this is going to go and cause the uh stimulation of my projection neuron so we have a stimulus here okay so we have we have not given any sensory input but we what did we find is that we have a stimulation of the projection neuron what if along with the sensory inputs you know along with the sensory inputs we gave the opioids so you have stimulated it here as well as you have given the opioids you are given the pain uh you have stimulated your uh kind of stimulating the inhibitory interneuron which is encephalinergic interneuron and they are going to release the encephalin so what is encephalin is going to do in kathleen is going to stimulate you know we have uh here they have kind of stimulated the morphine releasing uh stimulus is there here it was they have not stimulated those nausea septal neurons here they have stimulated the morphines you know they have given the morphines over here also they are giving the morphines at this level also and they are giving the end capillins here so what exactly is happening when you are giving the opioids you know either you give the uh stimulate and and careful energy neurons or you give any opioids what exactly you do you block the sensory input you kind of reduce the stimulation so you have a hyper polarization there so what about the extra epsp which is there in the projection neuron it has not reduced so now the pain perception has got reduced why because opioids either you give endogenous or exogenous endogenous is the one which is being released by the descending energetic pathway and so they block the channels and so if they block the channels there is no depolarization instead of depolarization there may be hyperpolarization and even if there is a depolarization the magnitude of depolarization is going to get reduced and so the perception of the pain is going to be reduced you know the impulses which is coming from your projection neurons they they are reduced and so the person doesn't feel the pain perception of pain is reduced