Nitric Oxide, Fatigue and Neuropathic Pain

EnVisage · Post by **EnVisage** » Sat Oct 25, 2003 3:31 pm

It has been noted that chronic pelvic syndrome (CPPS) has much in common with chronic fatigue syndrome (CFS) and fibromyalgia. For instance, many chronic prostatitis / chronic pelvic pain syndrome sufferers experience marked fatigue during periods of flare-up. And, like persons with CFS and fibromyalgia, many chronic prostatitis / chronic pelvic pain syndrome sufferers find that strenous physical activity can leave them "drained" for days after the exertion.

Researcher Martin Pall has proposed that excesses of nitric oxide (and its metabolite, peroxynitrite) may be responsible for many of the symptoms of CFS and fibromyalgia. The biochemical mechanisms involve overactivity of the N-methyl-D-aspartate (NMDA) receptors. The full text can be found at http://molecular.biosciences.wsu.edu/Fa ... _fibro.htm

The neurogenic inflammation / neuropathic pain model of chronic prostatitis / chronic pelvic pain syndrome likewise suggests overstimulation of NMDA receptors and remodelling of pain pathways in the sympathetic nervous system. Nitric oxide is one of several substances that plays a role in the pain and neurogenic inflammation.
http://www.chronicprosatitis.com
and
http://www.hosppract.com/issues/2000/07/brook.htm

There may be other similarities (at the neurochemical level) between CFS and CPPS. Addington notes that levels of the neurotransmitters dopamine and norepinephrine tend to be low in persons with CFS.
http://www.immunesupport.com/library/bu ... &PROD=PH35
Interestingly, tricyclic antidepressant (TCA) drugs often produce relief of symptoms in persons with neuropathic pain syndromes.
http://www.spineuniverse.com/displayart ... le391.html
Elavil, a TCA, has been suggested for management of chronic prostatitis / chronic pelvic pain syndrome pain.
http://www.chronicprosatitis.com
The TCAs function by blocking the re-uptake of the neurotransmitters serotonin and norepinephrine from nerve synapses. It is the potentiation of norepinephrine (rather than that of serotonin) that is thought to be responsible for the pain relief.
http://www.uspharmacist.com/ce/neuropat ... lt.htm#top
Addington notes that of the herbal treatments for CFS, St John's wort (hypericum) and kava appear to be the most effective.
http://www.immunesupport.com/library/bu ... &PROD=PH35
St John's wort is thought to work by raising synaptic levels of serotonin, norepinephrine and dopamine. Kava is thought to relieve pain by means of NMDA receptor blockade. It also relieves painful muscle spasm. (See my posting "Kava & St John's wort: ideal herbs for CPPS?" in the Phytotherapy and Nutrients section of this forum (30 May 2003)).

Elimination of certain foodstuffs (most notably the flavor enhancer MSG, and the artificial sweetener aspartame) may serve a significant role in the management of conditions involving overstimulation of the NMDA receptor. The following passage, from Martin Pall's article, explains the reasoning....
"Excessive NMDA activity is implicated in FM by three different types of studies. The most recent of these was recently reported by Smith et al, reporting that a subgroup of FM patients had a complete resolution of their symptoms by removing both monosodium glutamate (MSG) and aspartame from their diets. MSG and aspartame are both described as excitotoxins, because both glutamate from MSG and aspartate from aspartame, activate the NMDA receptors in the nervous system and may lead to neural damage as a consequence of excessive activation."
http://molecular.biosciences.wsu.edu/Fa ... _fibro.htm

If nitric oxide is responsible (in part, at least) for the pain and fatigue of CFS, chronic prostatitis / chronic pelvic pain syndrome and fibromyalgia, then it may well be beneficial to implement therapies aimed at combatting excesses of the chemical. Pall reveals that cobalamin (vitamin B12) is a nitric oxide "scavenger" and that therapeutic administration of the vitamin may help to alleviate symptoms of CFS and fibromyalgia.
Considering the similarities between these conditions and CPPS, it may be reasonable to assume that chronic prostatitis / chronic pelvic pain syndrome patients could likewise benefit from B12 therapy.

Post by **webslave** » Sat Oct 25, 2003 3:42 pm

That's a very well thought out theory, Mike.

If correct, it back my idea that chronic prostatitis / chronic pelvic pain syndrome is centrally mediated to some extent.

Gabriel · Post by **Gabriel** » Sat Oct 25, 2003 3:53 pm

I seem to remember JD sometimes prescribes Milgamma N to his patients, which is a vitamin B complex.

EnVisage · Post by **EnVisage** » Sun Oct 26, 2003 11:49 am

Hi, Mark.

Thanks for your response. I, too, am convinced that chronic prostatitis / chronic pelvic pain syndrome involves more than just a localised prostate inflammation. And it's the info on this site that got me pointed in that direction, specifically the item CAUSES>>COMPLEX REGIONAL PAIN SYNDROME. Since reading that, I've looked at numerous sites on complex regional pain syndrome (CRPS), aka reflex sympathetic dystrophy (RSD), and have been impressed by the similarities between this condition and CPPS. Even if they're not necessarily one and the same, there are some meaningful "overlaps". Two sites even present the reader with a RSD diet, and it's noteworthy that the suggested dietary modifications are almost identical to those that have been developed for control of CPPS.
This one is quite lenient....
http://www.rsdrx.com/four_f's_diet.htm

This next site has an interesting introduction to RSD, including some theories as to why some people are more prone than others to developing the condition. (Included is a theory that essentially combines the notion of autoimmune attack with that of remodelled pain pathways). There's also a RSD diet, one that is a bit more stringent than the first....
http://www.artzoo.com/health/rsdcrps.htm

It's interesting that these diets are based on the principle that one is seeking to counter excessive activity of the sympathetic division of the autonomic nervous system (i.e. diminish production of norepinephrine (NE) by avoiding caffeine, etc.). On the other hand, the TCA drugs (a mainstay for treating CRPS/RSD) work by raising levels of NE in the synapse, potentiating the effect of the neurotransmitter at alpha-2 adrenergic receptors. It would seem that the cause and the cure are one and the same (?) and it's an apparent paradox that I'm still grappling with....

Go well.

Post by **webslave** » Sun Oct 26, 2003 2:25 pm

The last page you reference is very interesting. It reads like a page on CPPS; the similarities are striking! However, it's not very scientific. The website (artzoo.com) belongs to a private non-medical individual, a CRPS patient, who does not reference any studies to back up her claims. Still, it is quite a compelling read for people with CP/IC/CPPS/PM. I think I wrote a while ago that I thought that PM could be a special form of CRPS.

EnVisage · Post by **EnVisage** » Sun Oct 26, 2003 6:06 pm

webslave wrote:However, it's not very scientific.

Yes, you're absolutely right. As soon as I saw the word "detox" (an overused and overhyped concept IMHO), I realised that it wasn't gonna be high science.

Go well.

Richard.N · Post by **Richard.N** » Mon Oct 27, 2003 5:59 pm

Addington notes that levels of the neurotransmitters dopamine and norepinephrine tend to be low in persons with CFS.

Ah. That'll be why even a low dose of Elavil crushed my fatigue

Are norepinephrine and noradrenaline the same thing by any chance? Opioids affect this as well (Ultram?).

EnVisage · Post by **EnVisage** » Tue Oct 28, 2003 8:01 am

Richard wrote:
"Are norepinephrine and noradrenaline the same thing by any chance? Opioids affect this as well (Ultram?)."

Yes, noradrenaline and norepinephrine are simply different names for the same chemical substance. This neurotransmitter is derived from another neurotransmitter, dopamine. Adrenalin (aka epinephrine), the related hormone, is produced in the adrenal glands, so called because they sit just above (ad) the kidneys (renal).
Opiates/opioids work at different receptor sites.
This page is an excellent intro to neurotransmitters....
http://www.benbest.com/science/anatmind ... html#intro

Go well.