Fight-Fright. We all know it. We have all felt it. For many of us getting sick seems to increase it and the usual parasympathetic (PNS) counterbalance works less well, thus leaving us in heightened overdrive a lot of the time (HPA axis dysfunction). We all know that this chronic stress state - where the pedal is always at the metal - is bad for us, but to really understand how it can become so important in the maintenance of the chronic illness state we need to know the steps. So, what is going on with this system and where can it go wrong when we have #MECFS #LongCovid. The names of the neurotransmitter and brain regions are important here - but dont fret. You do not need to remember the details. Its the gist of how the system gets stuck ON and how we can start to work towards OFF is what is important. Stage 1: The Threat - We perceive the threat through our senses *Even this very first step is dysfunctional in MECFS. because environmental sensitivity is itself a threat - just our regular senses become a potential danger trigger) Stage 2: Amygdala is activated and triggers fight-or-flight *The amygdala might be dysfunctional in MECFS picking up smaller events than it used too as being worth paying attention too (like a knock at the door or the phone ringing). Fear processing issues have been shown but structural brain studies are not super clear (however, there is a huge list of articles that mention amygdala on Health Rising. Stage 3: Hypothalamus is activated - The amygdala sends the distress signal to the hypothalamus (command center for the sympathetic nervous system (SNS). *the hypothalamus might be damaged in MECFS so this signal might be passed on more times or at lower levels of threat than what we see in healthy normals . see my latest "orexin' damage hypothesis. search "orexin (from:chydorina). * regardless - neuroinflammation is probably impacting function in both brain regions Stage 4. Sympathetic Nervous System (SNS) Activation - This is where things RAMP UP big time. Norepinephrine (noradrenaline) is released from adrenals - this is what prepares the body for action. As you read this list think about all the MECFS stuff that is ALREADY wonky with these systems (i.e. POTS). Norepinephrine causes: - the heart to beat faster - more blood to muscles and vital organs - Increase in blood pressure - Blood vessels constrict, to help deliver oxygen and nutrients more efficiently. - Airways in the lungs open wider, allowing for increased oxygen intake. - Increased glucose release (quick energy source) - Digestion and other non-essential functions slow down to conserve energy for immediate survival. ALL OF THIS USES A TON OF EXTRA ENERGY Stage 4: Adrenaline (Epinephrine) is Released - Simultaneously, the hypothalamus signals the adrenal medulla (part of the adrenal glands) to release adrenaline (epinephrine) into the bloodstream. * This double whammy of norepinephrine and adrenaline dials in the physiological responses above and also sharpens attention (which is energy-intensive). Energy use in eyes increases to better assess threat. EVEN MORE ENERGY IS BEING USED. Stage 5. HPA Axis Activation (Long-Term Response) -The above massive increase in arousal (aka energy-use in Stage 4) is obviously worrying and when we overlay all those physiological shifts onto someone who has POTS it is obvious how things could be wrong here. Its Stage 5 where the chronic stress system starts to break down. This is where the Hypothalamus-Pituitary-Adrenal (HPA) Axis changes to try and manage longer-term stress responses. -The hypothalamus releases corticotropin-releasing hormone (CRH), which prompts the pituitary gland to release adrenocorticotropic hormone (ACTH). ACTH travels to the adrenal cortex, stimulating the release of cortisol. Aha!! Finally we get to cortisol (and whether yours is low or high, we know that cortisol dysregulation is seen in MECFS). -Cortisol is known as the "stress hormone". It sustains the body's heightened alertness and energy levels. It promotes glucose production (not great for us), suppresses the immune system to prevent overreaction (really not great for us), and helps maintain blood pressure. -When our HPA axis becomes dysfunctional cortisol is overproduced and can lead eventually to not enough cortisol being produced. Cortisol is also required to turn OFF this response. So dysfunctional cortisol production can have major effects. Stage 6. Return to Baseline (Parasympathetic Nervous System Activation) - Finally we are realizing that the phone ringing is not a serious threat but because our HPA axis is dysfunctional the normal parasympathetic response does not get triggered. We often see dysfunctional ANS (autonomic nervous system), too high SNS (sympathetic nervous system, hence why Beta-Blockers can be helpful), too low PNS (parasympathetic nervous system). It can also be more complicated than this. *this is where VAGAL stimulation might help. we need to re-teach our bodies to RESOLVE the threat. - The body is now trying to get back to "Rest and Digest" - the counteract the SNS with the PNS. - To help this the PNS releases Acetylcholine: *Acetylcholine (ALCAR + alpha GPC help here could help here. nicotine mimics acetylcholine) - slows the heart rate - decreases blood pressure - promotes relaxation of muscles and digestion. *The levels of norepinephrine and adrenaline in the bloodstream decrease allowing the body to return to a state of homeostasis. Stage 7: In healthy normals this is where we get homeostasis and recovery Cortisol levels decline signaling that we do not need to be on alert. Recovery: In healthy normals the body focuses on repairing any damage caused by the stress response, replenishing energy stores, and restoring balance to physiological systems. This is obviously much harder in MECFS. The Stress Response System itself seems to be broken. The body can still turn ON the stress, its the process of turning it OFF where the problem seems to lie. *Unfortunately, this is another break in the chain as recovery takes ENERGY and we have probably used up all the reserves in the STRESS RESPONSE. Like with most dysfunctions in MECFS we see strong evidence at almost all the steps in the fight-fright response where things can go wrong because of other dysfunctions we experience (like POTS). When you re-read this - focus on where in the chain of steps you think you might have dysfunctions. We can use supplements and interventions at various stages alone this chain to help it function better. For me focusing on the Stage 1 and Stage 6 have yielded the best results. This has meant learning to react less and to activate the PNS (vagal stimulation, yoga nidra). I also take many supplements (some listed above) to help support these pathways. sign up for @behlthi (we are just getting started but lots of good collaborations are in the works).Neuroprotective actions of norepinephrine in neurological diseases

Fight-Fright. We all know it. We have all felt it. For many of us getting sick seems to increase it and the usual parasympathetic (PNS) counterbalance works less well, thus leaving us in heightened overdrive a lot of the time (HPA axis dysfunction). We all know that this chronic stress state - where the pedal is always at the metal - is bad for us, but to really understand how it can become so important in the maintenance of the chronic illness state we need to know the steps. So, what is going on with this system and where can it go wrong when we have #MECFS #LongCovid. The names of the neurotransmitter and brain regions are important here - but dont fret. You do not need to remember the details. Its the gist of how the system gets stuck ON and how we can start to work towards OFF is what is important. Stage 1: The Threat - We perceive the threat through our senses *Even this very first step is dysfunctional in MECFS. because environmental sensitivity is itself a threat - just our regular senses become a potential danger trigger) Stage 2: Amygdala is activated and triggers fight-or-flight *The amygdala might be dysfunctional in MECFS picking up smaller events than it used too as being worth paying attention too (like a knock at the door or the phone ringing). Fear processing issues have been shown but structural brain studies are not super clear (however, there is a huge list of articles that mention amygdala on Health Rising. Stage 3: Hypothalamus is activated - The amygdala sends the distress signal to the hypothalamus (command center for the sympathetic nervous system (SNS). *the hypothalamus might be damaged in MECFS so this signal might be passed on more times or at lower levels of threat than what we see in healthy normals . see my latest "orexin' damage hypothesis. search "orexin (from:chydorina). * regardless - neuroinflammation is probably impacting function in both brain regions Stage 4. Sympathetic Nervous System (SNS) Activation - This is where things RAMP UP big time. Norepinephrine (noradrenaline) is released from adrenals - this is what prepares the body for action. As you read this list think about all the MECFS stuff that is ALREADY wonky with these systems (i.e. POTS). Norepinephrine causes: - the heart to beat faster - more blood to muscles and vital organs - Increase in blood pressure - Blood vessels constrict, to help deliver oxygen and nutrients more efficiently. - Airways in the lungs open wider, allowing for increased oxygen intake. - Increased glucose release (quick energy source) - Digestion and other non-essential functions slow down to conserve energy for immediate survival. ALL OF THIS USES A TON OF EXTRA ENERGY Stage 4: Adrenaline (Epinephrine) is Released - Simultaneously, the hypothalamus signals the adrenal medulla (part of the adrenal glands) to release adrenaline (epinephrine) into the bloodstream. * This double whammy of norepinephrine and adrenaline dials in the physiological responses above and also sharpens attention (which is energy-intensive). Energy use in eyes increases to better assess threat. EVEN MORE ENERGY IS BEING USED. Stage 5. HPA Axis Activation (Long-Term Response) -The above massive increase in arousal (aka energy-use in Stage 4) is obviously worrying and when we overlay all those physiological shifts onto someone who has POTS it is obvious how things could be wrong here. Its Stage 5 where the chronic stress system starts to break down. This is where the Hypothalamus-Pituitary-Adrenal (HPA) Axis changes to try and manage longer-term stress responses. -The hypothalamus releases corticotropin-releasing hormone (CRH), which prompts the pituitary gland to release adrenocorticotropic hormone (ACTH). ACTH travels to the adrenal cortex, stimulating the release of cortisol. Aha!! Finally we get to cortisol (and whether yours is low or high, we know that cortisol dysregulation is seen in MECFS). -Cortisol is known as the "stress hormone". It sustains the body's heightened alertness and energy levels. It promotes glucose production (not great for us), suppresses the immune system to prevent overreaction (really not great for us), and helps maintain blood pressure. -When our HPA axis becomes dysfunctional cortisol is overproduced and can lead eventually to not enough cortisol being produced. Cortisol is also required to turn OFF this response. So dysfunctional cortisol production can have major effects. Stage 6. Return to Baseline (Parasympathetic Nervous System Activation) - Finally we are realizing that the phone ringing is not a serious threat but because our HPA axis is dysfunctional the normal parasympathetic response does not get triggered. We often see dysfunctional ANS (autonomic nervous system), too high SNS (sympathetic nervous system, hence why Beta-Blockers can be helpful), too low PNS (parasympathetic nervous system). It can also be more complicated than this. *this is where VAGAL stimulation might help. we need to re-teach our bodies to RESOLVE the threat. - The body is now trying to get back to "Rest and Digest" - the counteract the SNS with the PNS. - To help this the PNS releases Acetylcholine: *Acetylcholine (ALCAR + alpha GPC help here could help here. nicotine mimics acetylcholine) - slows the heart rate - decreases blood pressure - promotes relaxation of muscles and digestion. *The levels of norepinephrine and adrenaline in the bloodstream decrease allowing the body to return to a state of homeostasis. Stage 7: In healthy normals this is where we get homeostasis and recovery Cortisol levels decline signaling that we do not need to be on alert. Recovery: In healthy normals the body focuses on repairing any damage caused by the stress response, replenishing energy stores, and restoring balance to physiological systems. This is obviously much harder in MECFS. The Stress Response System itself seems to be broken. The body can still turn ON the stress, its the process of turning it OFF where the problem seems to lie. *Unfortunately, this is another break in the chain as recovery takes ENERGY and we have probably used up all the reserves in the STRESS RESPONSE. Like with most dysfunctions in MECFS we see strong evidence at almost all the steps in the fight-fright response where things can go wrong because of other dysfunctions we experience (like POTS). When you re-read this - focus on where in the chain of steps you think you might have dysfunctions. We can use supplements and interventions at various stages alone this chain to help it function better. For me focusing on the Stage 1 and Stage 6 have yielded the best results. This has meant learning to react less and to activate the PNS (vagal stimulation, yoga nidra). I also take many supplements (some listed above) to help support these pathways. sign up for @behlthi (we are just getting started but lots of good collaborations are in the works). ... Neuroprotective actions of norepinephrine in neurological diseases ...