attacking RSD induced swelling with diuretics [not]
 

For a while I've been trying to figure out why there wasn't anything I could find in the literature on the treatment of CRPS-induced swelling with a class of drugs called diuretics, basically drugs designed to increase kidney functioning as a way of removing excess fluids from the body. My interest having been piqued by the ballooning of my feet over the last few months, six years into RSD/CRPS, to to point that over the last couple of weeks I haven't been able to fit into one of two pairs of sandals that had stood me in good stead through August and September.

Turns out that the stumbling block on the use of diuretics for CRPS induced swelling was over a significant point, wherein the concurrent use of diuretics and narcotics tends to produce something called orthostatic hyotension "(also known as postural hypotension, orthostatic intolerance and, colloquially, as head rush or a dizzy spell) is a sudden fall in blood pressure, typically greater than 20/10 mm Hg, that occurs when a person assumes a standing position, usually after a prolonged period of rest." http://en.wikipedia.org/wiki/Orthostatic_hypotension

After waiting for a call this evening from my internist/cadiologist, he faxed me a letter instead, suggesting that my best options were continuing my restriction of salt, which is already very low, wearing support stockings (a non-starter where I can't tollerate any compresssion around my ankles) and keeping my legs" elevated [above my heart] as much as possible." A certainly well meaning suggestion . . . .

So it goes and now we know.

Mike

Mike,

What wonderful helpful advice:rolleyes:
I am sure that soon your oedema will be just a distant memory:wink:
To be honest, all my doctor says "Neurogenic Oedema is the most difficult to treat." This of course is no help when you feel as though you limbs are going to split like over cooked hot dogs!

Sorry I can't be any help
Tayla:hug:

Hi Mike,
 

I showed my right foot to my Dr. a couple of weeks ago. It is doing the same thing as yours and I can't wear certain shoes. I wear sandels in the summertime but in the winter it's going to be a harder problem. My RSD is worse in my right foot up to my knee, second to my right arm and hand and my pelvic/hip area.

I did buy Morton's light salt to see if that might help but so far it hasn't. It's got half the sodium in it. You might want to try it and see if it will help some. So far it hasn't for me but I like popcorn at night for a snack and I have been pouring it on so I might be using to much of it.

Who knows, nothing might do it. Like you, I have had the RSD since 98 and this is the first time I have delt with the swelling in the foot and leg.

Sorry to hear you are having this and I do hope it starts calming down for you.

Ada

Hi
 

My leg is like yours. It is really swollen from the knee downwards. I cannot wear any shoes, I used to be able to get sandals on but now I cant because of the swelling and hypersenstivity.
Before I developed RSD I was a size 4 in shoes (I am only 12) and after I developed RSD it went to a size 6 on my bad leg and a 4 on my good leg!
I have asked my physiotherapist if she's got any shoes that I can wear, but they will not supply me any!
Thanks for the advice Mike
Alison

I have had that...
 

My doctor gives me the diuretics for when the swelling gets to be full body. He told me just take for a couple days to help relieve the discomfort of all the swelling. It works usually in one dose, and I feel much better by the next day.

He did warn me to stand up slow, and if I have to, hang on to something. Really, I havent had much trouble with dizzyness though. I am totally salt free, except for what is already in the food, and it was a chore to get the salt intake down because of the flavor factor. It does help alot to get the salt intake down to as low as possible.

I am just now getting over the flu, and my wife bought some chicken soup mix to give us something for nourishment. Oh man each sip of the broth was like eating a teaspoon of salt! I never remembered the flavor of this kind of soup being that salty lol.

Back in my healthy days, I worked out with heavy weights 4 days a week. I learned early on that drinking alot of water was a good habit. If you didnt drink enough water the body would retain water, because it knew it wasnt getting enough compared to what was going out. But if you drank lots of water, the brain would tell the body to stop retaining water, and it would start releasing water. This would help flush out toxins and such in the system.

Now if I could just find a doctor to prescribe some pain relief, life would be much more enjoyable :)

Hi Jose,
 

I have heard of drinking water to help with swelling. I do drink a lot of water everyday but it hasn't helped with the swelling.

I forgot to say also all of my fingers are swollen. I have had to take all of my rings off. The only one I still have on is my wedding ring and I am hesitant about taking it off yet but I have to use butter to get it off. This just started awhile back.

My right hand is the worst but I am having surgery on it next Thursday. I think some of the swelling on my right hand is from my injured finger but I do know it's not all that due to my left hand being the same.

It would be interesting to find out what your Dr. says Jose. Any input would be good.

Ali, could you buy 2 pair of shoes to get two different sizes. I know it could get expensive if you buy very many pair but maybe one good expensive set would help for when you have to go places.

Thanks for this thread Mike, maybe we can learn from others how to deal with some of the swelling.

Ada

Thank you all for your input on this one.

For the record, the particular diuretic we were looking at is called Aldactone, and I have the following from its U.S. (FDA approved) prescribing information sheet:

Drug interactions:
* * *
Alcohol, barbiturates, or narcotics: Potentiation of orthostatic hypotension may occur.

http://www.pfizer.com/pfizer/downloa..._aldactone.pdf

And Jose, to the extent that you could get more information of any kind from your doctor - including citations in the literature - to "fighting water with water," it would be greatly appreciated.

Thanks again.

Mike

hi mike

thanks for that - i have had orthostatic hypotension for a year or more (not sure of dates!) and I have been on diuretics to try and reduce the full body swelling I was getting (and it was agony to pee because of the retention etc). Anyway I did realise that the hypotension got worse with the diuretic but just blamed it on...RSD (most things are attributable to it).

Ali - go to somewhere like foot locker as they are pretty cheap and get the backless trainers, on in a small size and one in the larger size. Alternatively buy one large pair and then wear that with your bad leg and wear another one you already own on your good leg. I have had HORRENDOUS swelling in the past (3 times the size of a normal limb to the point where my skin has cracked/ split which thankfully lowered after a year or so) and because the physios wanted to desense me they just took a pair of scissors to a pair of backless shoes I owned and split them down the middle until I could get my feet inside. It actually worked really well even though the shoes were ruined but it meant I could go a size up and have something on my feet. Weird - when I was walking/ crutching I could wear shoes not socks. Since I've been in a wheelchair I can wear socks (mostly) not shoes. Just an odd thought.

Love ya

Frogga xxxx

Dear Frogga -

I have requested this article from my friend who has access to such things:

"Neurokinin mediation of edema and inflammation," Campos MM, Calixto JB, Neuropeptides 2000 Oct; 34(5):314-22.

The aim of this article is to furnish a brief review of the role played by neurokinins in the inflammatory process. Further attention is given to the mechanisms, as well as to the receptor subtypes involved in neurokinin-mediated inflammation, in an attempt to clarify the participation of neurokinins in different models of acute and chronic inflammation. The involvement of SP, NKA and NKB is also examined in relation to the major signs of inflammation, including edema formation, protein plasma extravasation and vasodilatation. Finally, we provide a general overview on the potential clinical applications of neurokinin antagonists, along with the involvement of neurokinins in human diseases.

It sounds interesting. Edema - or oedema for our friends in the Commonweath - obviously ties into an inflammatory process, it would just be nice to understand the mechanism in a little more detail. I'll make the article available, when and as it falls into my hands.

Mike

http://www.pubmedcentral.nih.gov/art...medid=17362934

This is interesting

And here's the article I had found earlier on Neurokinin mediation of edema and inflamation:

Diuretics are dangerous for RSD
 

Hi Mike,
It is my understanding that diuretics are dangerous for RSd. the reason I was told is because our edema is caused by fluid ,being held or leaked within the nerve cell. Not the typical tissue swelling. Direutics work for people that have connective tissue disorders etc as the swelling is in the tissues. When you have RSD and take diruetics, it increases muscle spasms and dysfunction.
Not a good thing for us.Jose had good advise on drinking more water. We generally are dehydrated and just the nature of RSD keeps our limbs from being supplied adquetaly with blood flow which also moves water through our bodies.Our edema is very unique like every thing else with this disease. I had so much fluid once in both legs, from the nerve cells, I was hospitalized and they successfully removed seven pounds of fluid from each leg- but with a ketamine infusion and another medicine that starts with an m... mizondian - something like that sorry I cant remember the name-it is listed in Dr. Hoosmands puzzles. Hope this helps. My primary, thinking she was helping put me on a diruetic recently due to my upper back swellling. The spasms almost killed me- she quickly told me to stop taking it. When I told my Rsd doctor this he explained to me why the diruetic was not right for us. I hope this helps. Good luck. cz

trying to put it all together
 

What's real interesting here is how when you begin to look at look at the use of Neurokinins in the control of edema, as set forth in the article I posted above, and underlying the neuro-immunolgical model of edema, the first question that comes up is - of course - what's a Neurokinin?

Now, the good folks who give us our little online medical dictionary have an answer for that, "a mammalian decapeptide tachykinin found in the central nervous system. It is similar in structure and action to substance p and neurokinin k. The compound has bronchoconstrictor, smooth muscle constrictor, and hypotensive effects and also activates the micturition reflex."

But that isn't as hard as it seems. First, a decapeptide is defined in turn simply as "an oligopeptide [a peptide of a small number of component amino acids as opposed to a polypeptide] containing 10 amino acids."

But here comes the interesting part. A tachykinin is defined as "Any member of a group of polypeptides, widely scattered in vertebrate and invertebrate tissues, that have in common four of the five terminal amino acids: Phe-Xaa-Gly-Leu-Met-NH2; pharmacologically, they all cause hypotension in mammals, contraction of gut and bladder smooth muscle, and secretion of saliva." Note the key word here: hypotension.

Now consider a somewhat different definition of Neurokinins in the article posted above:

Neurokinins form a family of peptides that include substance P (SP), neurokinin A (NKA) and neurokinin B(NKB). These peptides are largely distributed throughout the central and peripheral nervous system, being localized in capsaicin-sensitive neurons.

"Neurokinin mediation of edema and inflammation," Campos MM, Calixto JB, Neuropeptides 2000 Oct; 34(5): 314 at 314.

And then the following:

The participation of neurokinins and their receptors at inflammatory events has been demonstrated by a great amount of pharmacological and biochemical studies, indicating their importance in most pathological responses. One of the main alterations evoking the increase in neurokinin levels is sensorial nerve damage. The destruction of neuronal terminals may occur following inflammatory chronic diseases or in response to some noxious stimulus, such as the application of chemical agents or burns. The characterization of the main alterations in the neurokinin system may constitute an attractive and relevant alternative for the development of new therapeutic agents. The aim of the present review is to highlight the recent progress in the area of neurogenic inflammation, with an emphasis on the roles exerted by neurokinins in this scenario.

Id at 315.

But then getting back to the the slightly more generic issue of tachykinins, check out the exhaustive survey article, "The Tachykinin Peptide Family," Cinzia Severini et al, Pharmacological Reviews, 54: 285–322, 2002, available online at http://pharmrev.aspetjournals.org [or just send me a PM with your email address for a copy], and it's discussion under the topic heading "Neurogenic Inflammation," at 313-14":

Electrical, mechanical, and chemical stimulation of the C-fibers in sensory neurons causes an axon reflex taking place in the branchings of sensory nerves. The consequence is the neurogenic inflammation: pain, vasodilation (flare), and plasma extravasation.

Antidromic vasodilation is mediated by a neurotransmitter at the sensory nerve endings in the skin. Similarly, plasma extravasation elicited by antidromic stimulation also seemed to be provoked by a mediator released from pain sensitive nerve terminals (Jancso et al., 1967).

Among the many transmitters suggested in this connection were acetylcholine, noradrenaline, ATP, bradykinin, histamine, 5-HT, and prostaglandins. At the present time, SP fulfills the criteria for being accepted as the main mediator for all components of antidromic stimulation (Lembeck and Holzer, 1979; Pernow, 1985).

i. SP is present in the C-fibers of the sensory neurons and is released from these fibers during antidromic stimulation.

ii. Close arterial administration of SP causes vasodilation and plasma extravasation, thus, mimicking the effect of antidromic stimulation.

iii. Capsaicin, which depletes SP in sensory neurons, almost completely blocks vasodilation and neurogenic plasma extravasation.

The above criteria were completed and remarkably strengthened by more recent data:

iv. The nociceptin/orphanin-induced nociceptive response is brought about in mice by SP release from peripheral endings of nociceptive primary afferent neurons (Inoue et al., 1998), supporting the view that also pain in neurogenic inflammation is due to release of SP.

v. In mutant mice with disrupted preprotachykinin A gene, neurogenic inflammation produced by topical application of capsaicin was almost absent, whereas in non-neurogenic paw edema produced by complete Freund’s adjuvant neurogenic inflammation was the same in wild-type and mutant mice (Cao et al., 1998). However, there is some doubt about the fact that SP is the unique direct or indirect (through release of histamine from the mast cells) agent responsible for the vasodilation and plasma extravasation seen in neurogenic inflammation. Two points deserve attention. The first is that SP is costored and coreleased from sensory nerve endings with calcitonin gene-related peptide, which displays a potent edema producing activity; the second is that the histamine-releasing activity of SP, which remarkably contributes to plasma extravasation and edema, has been attributed not to the intact SP molecule but to its N-terminal fragment (1–7). Moreover there are data, which need confirmation, showing that antidromic stimulation may not always release SP but other active agents.

In summing up, there is little doubt that neurogenic inflammation represents the most striking and credible example of a decisive, if not unique, involvement of SP in a physiopathological process.

Then in the same vein, we also have "Neurokinins enhance excitability in capsaicin responsive DRG neurons," Adrian Sculptoreanu and William C. de Groat, Exp. Neurol. 2007 May; 205(1): 92–100 [and once more, I'll be happy to send anyone a copy of this who wants it]:

Abstract

Neurokinins released by capsaicin-responsive (C-R) dorsal root ganglia neurons (DRG) may control firing in these neurons by an autofeedback mechanism. Here we used patch clamp techniques to examine the effects of neurokinins on firing properties of dissociated DRG neurons of male rats. In C-R neurons that generated only a few action potentials (APs, termed phasic) in response to long depolarizing current pulses (600 ms), substance P (SP, 0.5 μM) lowered the AP threshold by 11.0 ±0.3 mV and increased firing from 1.1±0.7 APs to 5.2±0.6 APs. In C-R tonic neurons that fire multiple APs, SP elicited smaller changes in AP threshold (6.0±0.1 mV reduction) and the number of APs (11±1 vs. 9±1 in control). The effects of SP were similar to the effect of heteropodatoxin II (0.05μM) or low concentrations of 4-aminopyridine (50 μM) that block A-type K+ currents. A selective NK2 agonist, [βAla8]-neurokinin A (4–10) (0.5 μM), mimicked the effects of SP. The effects of SP in C-R phasic neurons were fully reversed by an NK2 receptor antagonist (MEN10376, 0.5 μM) but only partially by a protein kinase C (PKC) inhibitor (bisindolylmaleimide, 0.5 μM). An NK3 selective agonist ([MePhe7]-neurokinin B, 0.5 μM), an NK1 selective agonist ([Sar9, Met11]-substance P, 0.5μM) or activation of PKC with phorbol 12, 13-dibutyrate (0.5 μM) did not change firing. Our data suggest that the excitability of C-R phasic afferent neurons is increased by activation of NK2 receptors and intracellular signaling mediated only in part by PKC.

All of which leads me, full circle, back to the thread I posted a couple of weeks ago, "Sodium Channel Blockers Make it Big or The Holy Grail in Pain Science":

Jim Broatch of the RSDSA just forwarded a press release, dated October 3, 2007, in which this work was referred to as meeting "The Holy Grail in pain science is to eliminate pathologic pain without impairing thinking, alertness, coordination, or other vital functions of the nervous system," by the director of the National Institute of Neurological Disorders and Stroke (NINDS) at NIH:

TREATMENT BLOCKS PAIN WITHOUT DISRUPTING OTHER FUNCTIONS

A combination of two drugs can selectively block pain- sensing neurons in rats without impairing movement or other sensations such as touch, according to a new study by National Institutes of Health (NIH)-supported investigators. The finding suggests an improved way to treat pain from childbirth and surgical procedures. It may also lead to new treatments to help the millions of Americans who suffer from chronic pain. The study used a combination of capsaicin -- the substance that makes chili peppers hot -- and a drug called QX-314. This combination exploits a characteristic unique to pain-sensing neurons, also called nociceptors, in order to block their activity without impairing signals from other cells. In contrast, most pain relievers used for surgical procedures block activity in all types of neurons. This can cause numbness, paralysis and other nervous system disturbances.

"The Holy Grail in pain science is to eliminate pathologic pain without impairing thinking, alertness, coordination, or other vital functions of the nervous system. This finding shows that a specific combination of two molecules can block only pain- related neurons. It holds the promise of major future breakthroughs for the millions of persons who suffer with disabling pain," says Story C. Landis, Ph.D., director of the National Institute of Neurological Disorders and Stroke (NINDS) at the NIH, which funds the investigators' research along with the National Institute of Dental and Craniofacial Research (NIDCR) and the National Institute of General Medical Sciences (NIGMS). The study appears in the October 4, 2007, issue of "Nature". [1]

[1] Binshtok AM, Bean BP, Woolf CJ. "Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockers." "Nature", October 4, 2007, Vol. 449, No. 7162, pp. 607-610.

http://neurotalk.psychcentral.com/sh...ghlight=sodium

So as soon as they are ready, count me in on the chili peppers. (Unless I try out something else altogether first.)

Mike

Your mention of my article brought me to this forum...there is actually a connection between neurokinins and Na channels in nociceptive (pain) neurons which I am presently investigating. Turns out that neurokinins stimulate Na channles; particularly the tetrodotoxin-resistant subtype (Nav1.9) which has more recently been associated with development of chronic pain; that may account in part for the increase in excitability caused by neurokinins. There is a wide interest in the pharmaceutical industry at present to develop drugs that are selective blockers of this Na channel subtype and it is hope may selectively influence (inhibit) abnormal electrical activity in pain neurons. We have evidence to support this assertion:
"26. Yamane H, de Groat WC, Sculptoreanu A. (2007) Effects of ralfinamide, a Na+ channel blocker, on firing properties of nociceptive dorsal root ganglion neurons of adult rats. Exp Neurol. 208(1):63-72."

To qote the highlight of one of my colleagues (Michael Gold):

Thanks for discussing my articles, I am the guy who did the work, Adrian Sculptoreanu. There are many interesting things still emerging from my early studies..among them Na channels are definitely a target of neurokinin modulation via erk kinase. That could be theoretically why during inflammation phosphorylated channels have higher affinities for certain local anesthetics. The autofeedback mechanism responsible for switching on C-fiber neurons are more complex and may involve several channels that may include TRP in addition to a slew of voltage dependent channels. For example SP and endothelin (released by some tumors) interact synergistically to produce very large increases in depolarizing TRPC currents (non selective cation channels)...so if I had the money to continue this research there are many dfirections it could take. For now I am in Italy enjoying the good weather...

do we have 2 Dr Adrians claiming to be the author worrying