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        New Message Board Archives >> Medications, Treatments, Therapies 2004 >> CH - Got Endorphins?
        
(Message started by: floridian on Aug 30th, 2004, 11:32am)
Title: CH - Got Endorphins?
Post by floridian on Aug 30th, 2004, 11:32am
Interesting.  The level of Nociceptin (an endorphin-like substance) in our blood drops by 50% when we go into a cluster period, then returns to normal when the period is over.  Nociceptin inhibits vasodilation.  Nociceptin can cause pain as well as block pain.


Quote:
Headache. 2004 Sep;44(8):852.      
   
   CLUSTER.

   [No authors listed]

   Ertsey C, Hantos M, Bozsik G, Tekes K. Circulating nociceptin levels during the cluster headache period. Cephalalgia. 2004;24:28-283. The trigeminal innervation of the dura and its vessels has a prominent role in the mechanism of cluster headache. Nociceptin, an opioid neuropeptide, is the endogenous ligand of the OP-4 receptor, with both algesic and analgesic properties depending on the site of action. Nociceptin and its receptor are expressed by trigeminal ganglion cells where they colocalize with calcitonin gene-related peptide (CGRP), a marker peptide of the trigeminovascular neurones. Nociceptin inhibits neurogenic dural vasodilatation, a phenomenon related to trigeminovascular activation. To explore its possible involvement in cluster headache, we studied circulating levels of nociceptin when attack-free during the cluster period, and also after the termination of the cluster period, using radioimmunoassay. In 14 cluster headache patients nociceptin levels during the cluster period were significantly lower than in age-, and sex-matched controls (4.91 +/- 1.96 vs. 9.58 +/- 2.57 pg/ml; P <.01). After the termination of the cluster period nociceptin levels (8.60 +/- 1.47 pg/ml) were not statistically different from controls. Nociceptin levels did not correlate with age, length of disease, or episode length. Lower nociceptin levels during the cluster period may result in a defective regulation of trigeminal activity that might not protect sufficiently against the attacks.


Nociceptin is a polypeptide ('mini-protein' made of amino acids).  The sequence of amino acids is symbolized as:
http://www.peptide.co.jp/eng/new/pinews/nocicptn.gif
(if you hack with amino acids, this could be put together fairly easily)
Title: Re: CH - Got Endorphins?
Post by Margi on Aug 30th, 2004, 11:55am
fascinating!

This must be why an attack is usually aborted when a sufferer is put into a sudden crisis situation (ex. a supporter I know tripped and fell HARD while bringing her cluster hubby an ice pack - he was SO worried that she'd broken something and rushed to help her, *presto* instant abort) - maybe it's the endorphin surge and not the adrenaline surge?  or maybe both?

so how do we manufacture synthetic endorphins as abortives?

you do great research, Floridian.  Thank you!
Title: Re: CH - Got Endorphins?
Post by floridian on Aug 30th, 2004, 12:06pm
There are ways of synthesizing endorphins, but I don't know about toxicity.  Some endorphins are very potent, and over dosing could cause problems.  Some clinical trials are needed first.

As milk protein is digested, some endorphin like compounds are created - these cause relaxation (a glass of warm milk before bed) and other pharmacological effects (nasal congestion).  


Quote:
Curr Pharm Des. 2003;9(16):1331-44.      

   Opioid receptor ligands derived from food proteins.

   Teschemacher H.

   During the last two decades a variety of food protein fragments has been demonstrated to elicit biological effects in various in vitro or in vivo test systems. A considerable part of these bioactive peptides are opioid receptor ligands, which may be regarded as exogenous supplements to the endogenous opioidergic systems of the human organism. Most of these food-derived opioid receptor ligands are fragments of the milk proteins alpha-, beta- or kappa-casein, alpha-lactalbumin, beta-lactoglobulin or lactotransferrin; however, also wheat gluten, rice albumin, bovine serum albumin or hemoglobin, i.e. possible constituents of meat, and even a protein from spinach could be demonstrated to contain fragments behaving like opioid receptor ligands. Practically all of these compounds display opioid agonist activity; only very few of them behave like opioid antagonists. Bioactive food protein derivatives have been termed " food hormones", which implies that these compounds display their bioactivities when released from food constituents, i.e. from their precursor molecules due to the action of gastrointestinal enzymes. The critical point in case of food protein-derived opioid receptor ligands is that only a minority of their bioactive effects demonstrated as yet has been observed upon oral or intragastric administration of these peptides or their precursor proteins and that most of these studies have been performed in animals. Thus, in terms of "evidence-based dietary supplementation" more studies are needed to prove effects of food protein-derived opioid receptor ligands or their precursors after oral administration in humans and, moreover, to prove a benefit for the consumer's organism.



Quote:
Br J Nutr. 2000 Nov;84 Suppl 1:S27-31.      
   
   Opioid peptides encrypted in intact milk protein sequences.

   Meisel H, FitzGerald RJ.

   Opioid agonistic and antagonistic peptides which are inactive within the sequence of the precursor milk proteins can be released and thus activated by enzymatic proteolysis, for example during gastrointestinal digestion or during food processing. Activated opioid peptides are potential modulators of various regulatory processes in the body. Opioid peptides can interact with subepithelial opioid receptors or specific luminal binding sites in the intestinal tract. Furthermore, they may be absorbed and then reach endogenous opioid receptors.
Title: Re: CH - Got Endorphins?
Post by Redd715 on Aug 30th, 2004, 12:24pm
Daymn it sucks.....

CH and Lactose intolerant to boot!  Guess I'm really screwed!  [smiley=laugh.gif] [smiley=laugh.gif]
Title: Re: CH - Got Endorphins?
Post by FZfan on Aug 30th, 2004, 12:41pm
Doesn't sex release endorphins into the blood? Or am I way off base here?
Title: Re: CH - Got Endorphins?
Post by floridian on Aug 30th, 2004, 12:49pm
Alas, sex does not increase endorphin.  On the positive side, there are lactose free dairy products - the milk sugar is not related directly to the protein/endorphins. In fact, some fermented foods that are low lactose/lactose free might be the best source for endorphin like compounds. Not sure that dairy endorphins are the same as nociceptin, but maybe??  


Quote:
Psychosom Med. 1999 May-Jun;61(3):280-9.      

   Comment in:

       * Psychosom Med. 1999 May-Jun;61(3):290-1.

   
   Cardiovascular and endocrine alterations after masturbation-induced orgasm in women.

   Exton MS, Bindert A, Kruger T, Scheller F, Hartmann U, Schedlowski M.

   Department of Medical Psychology, University Clinic Essen, Germany.

   OBJECTIVE: The present study investigated the cardiovascular, genital, and endocrine changes in women after masturbation-induced orgasm because the neuroendocrine response to sexual arousal in humans is equivocal. METHODS: Healthy women (N = 10) completed an experimental session, in which a documentary film was observed for 20 minutes, followed by a pornographic film for 20 minutes, and another documentary for an additional 20 minutes. Subjects also participated in a control session, in which participants watched a documentary film for 60 minutes. After subjects had watched the pornographic film for 10 minutes in the experimental session, they were asked to masturbate until orgasm. Cardiovascular (heart rate and blood pressure) and genital (vaginal pulse amplitude) parameters were monitored continuously throughout testing. Furthermore, blood was drawn continuously for analysis of plasma concentrations of adrenaline, noradrenaline, cortisol, prolactin, luteinizing hormone (LH), beta-endorphin, follicle-stimulating hormone (FSH), testosterone, progesterone, and estradiol. RESULTS: Orgasm induced elevations in cardiovascular parameters and levels of plasma adrenaline and noradrenaline. Plasma prolactin substantially increased after orgasm, remained elevated over the remainder of the session, and was still raised 60 minutes after sexual arousal. In addition, sexual arousal also produced small increases in plasma LH and testosterone concentrations. In contrast, plasma concentrations of cortisol, FSH, beta-endorphin, progesterone, and estradiol were unaffected by orgasm. CONCLUSIONS: Sexual arousal and orgasm produce a distinct pattern of neuroendocrine alterations in women, primarily inducing a long-lasting elevation in plasma prolactin concentrations. These results concur with those observed in men, suggesting that prolactin is an endocrine marker of sexual arousal and orgasm.
Title: Re: CH - Got Endorphins?
Post by FZfan on Aug 30th, 2004, 1:03pm

on 08/30/04 at 12:49:31, floridian wrote:
Alas, sex does not increase endorphin.


Damn!  ;;D

Thanks floridian.
Title: Re: CH - Got Endorphins?
Post by Margi on Aug 30th, 2004, 2:31pm

on 08/30/04 at 12:49:31, floridian wrote:
Not sure that dairy endorphins are the same as nociceptin, but maybe??  


I would tend to think not as you said above it's a vasocontrictor...dairy doesn't do that, does it?

In my really uneducated opinion, I'd say it's closer to adrenaline - simply because of it's pain blocking/causing abilities.  Think of the story of the mom lifting a car off her kid - major adrenaline/endorphine? rush there.  Lots of cluster attacks aborted, like I said, with these rushes, too.  Stands to reason that if your levels are diminished while in cycle, a sudden surge COULD have abortive properties, just not enough to end your cycle.

Am I correct in assuming epinephrine is man-made adrenaline?  (My dentist says it is - that's why your heart beats faster when you get dental freezing so they have a non-adrenaline variety available for those with heart problems).  I hate to say the "m" word, but I've had this stuff abort an impending attack for me and have heard from another clusterhead that they felt they were going to get hit just before the dentist froze them - attack abort.  

I think there's really something to this theory, Floridian.  
Title: Re: CH - Got Endorphins?
Post by floridian on Aug 30th, 2004, 4:29pm
One class of milk derrived endorphins are the casomorphins. These mimic the action of the hormone somatostatin. (first abstract)

Somatostatin blocks Substance P mediated pain in cluster headaches! (second abstract)

I was a heavy milk drinker for my first 18 years.  Started drinking soft drinks in college.  Milk consumption was down near zero when the clusters started.


Quote:
Comp Biochem Physiol A Mol Integr Physiol. 2000 Nov;127(3):249-57.      
   
   Effects of intra-abomasal infusion of beta-casomorphins on circulating concentrations of hyperglycaemic insulin and glucose in dairy cows.

   Kim TG, Choung JJ, Wallace RJ, Chamberlain DG.

   The effects of intra-abomasal infusion of a mixture of -casomorphins on circulating concentrations of insulin and glucose prestimulated by either abomasal (experiment 1) or intravenous (experiment 2) glucose were studied using non-lactating dairy cows. In both experiments, bolus infusion of 240 mg of a mixture of three beta-casomorphins (beta-casomorphin-4-amide, -5 and -7) was given via an abomasal infusion line. The beta-casomorphins significantly lowered the responses of serum insulin to both abomasal and intravenous glucose infusions (P<0.05). However, the beta-casomorphins did not significantly affect circulating glucose concentrations. The insulinopenic action of the beta-casomorphins is consistent with the action of somatostatin-28 (SS-28) as judged from the effects of SS-28 on the insulin secretion when administered intravenously in experiment 1.




Quote:
Ric Clin Lab. 1987 Apr-Jun;17(2):155-62.      

   A pharmacological approach to the analgesizing mechanism of somatostatin in cluster headache.

   Caleri D, Marabini S, Panconesi A, Pietrini U.

   Vasodilation, conjunctival and nasal edema as well as miosis are symptoms associated with cluster headache (CH) attacks. Similar symptomatology is caused by substance P (SP) release from peripheral trigeminal nerve endings. The symptomatic effect of somatostatin (SRIF) during CH attacks was attributed to the inhibition of SP release from trigeminal neurons. This study was designed to evaluate both the vascular effect of SRIF on the dorsal hand vein and SRIF plasma levels prior to and after subcutaneous and intranasal administration in CH patients. A powerful venoconstriction and tachyphylaxis were demonstrated when SRIF was administered both as bolus and infusion. Plasma levels of SRIF in CH sufferers were lower than in control subjects. Subcutaneous and intranasal SRIF administrations induced maximal plasma levels after 5 and 10 min, respectively. These data suggest that SRIF plays an important role during CH attacks; however, its exact mechanism of action is still to be defined.
Title: Re: CH - Got Endorphins?
Post by floridian on Aug 30th, 2004, 4:51pm
Margi

epinephrine is adrenaline - it could be synthetic, or extracted from humans or animals - same thing.  Epinephrine does constrict the blood vessels, so that probably has some effect in fighting a cluster. As part of the fight-or-flight mechanism, it keeps blood away from the extremities.  It is also hard on the heart.

Not sure about milk and the blood vessels - I would think the calcium and potassium in milk would keep blood pressure low, don't know if that is from relaxing the blood vessels, or some other mechanism. Milk has so many different things, it may be that whole milk has little effect, but an extract of one component might be more effective.
Title: Re: CH - Got Endorphins?
Post by BobG on Aug 30th, 2004, 4:52pm
I've heard Margi's adrenaline theory (she'll have to explain it, I can't) and I think it has a great deal of merit.
Bob P has a serotonin/melatonin theory (He'll have to explain it, I can't) that fits in nicely with the adrenaline theory.

Adrenaline is a very powerful chemical and can be addicting. I would call it the Rambo syndrome. You know, a person always looking for one more thrill to get one more adrenaline rush.
Title: Re: CH - Got Endorphins?
Post by Margi on Aug 30th, 2004, 5:45pm
maybe all y'all should just take up skydiving or bungee jumping or roller coastering.  GREAT way to get a surge.

BobG - I'm not sure I really can explain it either.  I was counting on YOU to understand it and interpret it for me.  Sheesh.   ::)
Title: Adrenaline / Noradrenaline
Post by floridian on Aug 31st, 2004, 10:57am
Just came across an article on migraine that puts forward the idea that migraine is primarily a 'sympathetic nervous system disorder.'  According to that theory, migraine is due to low noradrenaline levels (and high prostaglandin/atp/dopamine).   Coincidentally, clusterheads have low sympathetic nervous system activity, and low norepinephrine.  

The amino acid phenylalanine is an essential building block (precursor) of both adrenaline and noradrenaline.  Wonder if this would help with the sympathetic deficit?? Phenylalanine reportedly helps with migraine pain, but some sources indicate that large doses of phenylalanine can trigger migraine, so this is not something to rush into. Pure phenylalanine can also interact with some meds - another reason not to leap.  Also along these lines, there is a new class of anti-depressants that are serotonin AND noradrenaline reuptake inhibitors.  These might help where SSRIs are not very effective in CH.

(continued)
Title: Adrenaline / Noradrenaline  part 2
Post by floridian on Aug 31st, 2004, 10:57am


Quote:
Headache. 2004 Jan;44(1):53-64.      
   
   Migraine: a chronic sympathetic nervous system disorder.

   OBJECTIVES: To determine the degree of diagnostic and clinical similarity between chronic sympathetic nervous system disorders and migraine. BACKGROUND: Migraine is an episodic syndrome consisting of a variety of clinical features that result from dysfunction of the sympathetic nervous system. During headache-free periods, migraineurs have a reduction in sympathetic function compared to nonmigraineurs. Sympathetic nervous system dysfunction is also the major feature of rare neurological disorders such as pure autonomic failure and multiple system atrophy. There are no known reports in the medical literature, however, comparing sympathetic nervous system function in individuals with migraine, pure autonomic failure, and multiple system atrophy. METHODS: A detailed review of the literature was performed to compare the results of a wide variety of diagnostic tests and clinical signs that have been described in these 3 heretofore unrelated disorders. RESULTS: The data indicate that migraine shares significant diagnostic and clinical features with both pure autonomic failure and multiple system atrophy, yet represents a distinct subtype of chronic sympathetic dysfunction. Migraine is most similar to pure autonomic failure in terms of reduced supine plasma norepinephrine levels, peripheral adrenergic receptor supersensitivity, and clinical symptomatology directly related to sympathetic nervous system dysfunction. The peripheral sympathetic nervous system dysfunction is much more severe in pure autonomic failure than in migraine. Migraine differs from both pure autonomic failure and multiple system atrophy in that migraineurs retain the ability, although suboptimal, to increase plasma norepinephrine levels following physiological stressors. CONCLUSIONS: The major finding of the present study is that migraine is a disorder of chronic sympathetic dysfunction, sharing many diagnostic and clinical characteristics with pure autonomic failure and multiple system atrophy. However, the sympathetic nervous system dysfunction in migraine differs from pure autonomic failure and multiple system atrophy in that occurs in an anatomically intact system. It is proposed that the sympathetic dysfunction in migraine relates to an imbalance of sympathetic co-transmitters. Specifically, it is suggested that a migraine attack is characterized by a relative depletion of sympathetic norepinephrine stores in conjunction with an increase in the release of other sympathetic cotransmitters such as dopamine, prostaglandins, adenosine triphosphate, and adenosine. An enhanced understanding of the sympathetic dysfunction in migraine may help to more effectively diagnose, prevent, and/or treat migraine and other types of headache.



Quote:
Schweiz Med Wochenschr. 1996 Jun 15;126(24):1054-61.      

   [Reduced sympathetic nervous system activity during the cluster period of cluster-headache]

   Cluster headache is a rare, very severe disorder that is clinically well characterized with a relatively poorly understood pathophysiology. Alterations of the hypothalamic-pituitary axis due to chronobiological changes, such as typical temporal pattern of both cluster periods and attacks, point to a central etiopathogenesis. Multiple local and systemic autonomic symptoms are compatible with an altered balance of the sympathetic and parasympathetic nervous system. In this connection, too, a central etiology is postulated. To evaluate the activation of the sympathetic nervous system, in 12 cluster headache patients we investigated the plasma catecholamines norepinephrine and epinephrine four times a day (7.00, 12.00, 17.00, 23.00) in the cluster period. In the cerebrospinal fluid we determined the transmitters norepinephrine, epinephrine, dopamine and the metabolites homovanillic acid (HVA), vanillymandelic acid (VMA) and 5-hydroxyindoleacetic acid (5-HIAA). Values of plasma norepinephrine in the morning (p < 0.01), in the evening (p < 0.01) and the daily mean value (223.8 = 58.3 nmol/ml) were significantly decreased in the cluster headache group in comparison to the control group (328.8 = 53.0 nmol/ml, p < 0.01). The plasma epinephrine showed no significant changes. In the CSF of cluster headache patients norepinephrine (p < 0.05), HVA (p < 0.01), and 5-HIAA (p < 0.01) were significantly decreased. Plasma norepinephrine was correlated with CSF values of HVA and 5-HIAA. The longer the duration of the disease, the lower the values of HVA and 5-HIAA in the CSF of cluster headache patients. Moreover, plasma norepinephrine showed a significant correlation with the duration, the intensity and the frequency of the attacks. The results of this study implicate decreased activity of the sympathetic nervous system with alteration of circadian rhythmicity during the cluster period. The decreased CSF transmitter values may support the hypothesis of a central etiopathogenesis of cluster headache. Moreover, plasma norepinephrine seems to be involved in triggering and continuing the attacks. The anatomical region in which this interface of sympathetic and neurogenic inflammatory processes might be located is the trigemino-vascular system.
Title: Re: CH - Got Endorphins?
Post by vig on Aug 31st, 2004, 11:17am
I sure appreciate your efforts, Floridian.
(even when I can't quite follow them all.)
I'm getting quite an education from you.
Thanks...

The neuro I went to told me to:
"keep your endorphins up"
I'm trying.
Title: Re: CH - Got Endorphins?
Post by Abaris on Sep 7th, 2004, 1:21pm
What about adrenochrome? It is derived from adrenoline. It also has been found to have effects similar to the mushrooms that are discussed on these message boards.
Title: Re: CH - Got Endorphins?
Post by pubgirl on Sep 7th, 2004, 5:57pm
Lots of interesting reading and rereading.

It may be coincidence, but I certainly feel that the NSAID (which is also a prostaglandin inhibitor) I take for a different problem often stops my migraines while I'm taking it.
Trouble is I haven't noticed it having any effect on my CH attacks. It has always seemed like more evidence to me that my migraines and CH attacks are not caused by/or result from or in the same things occurring in my head and body

An obvious (but unrelated to the above) question:

Has anyone synthesised Nociceptin?

Wendy


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