Article by Goldstein on Neuroscience

[Guest guest]

This Is - Los Angeles

Published in The National Forum - Winter 1998/99

By Jay A. Goldstein, M.D.

No, this is not the wraith of R. Morrow reporting to you as if

from

the London blitz, but this is Jay Goldstein reporting to you from the

floor

of the Los Angles Convention Center after attending five days of the

28th

Annual Meeting of the Society for Neuroscience, the largest and most

important conference in the world which is held every year. I try to

attend

whenever I can, and on this occasion I definitely am reporting from

the

floor of the Convention Center, where I am lying after being blitzed

by

12,000 experiments in five days. This averaged out to about 1,200

experiments every morning and 1,200 experiments every afternoon. This

meeting marks a watershed in my association and study of neuroscience.

Back in the early 1980s when the Society for Neuroscience was fairly

small,

I taught a course in medical neurobiology for psychiatry residents. I

had to

invent this course because there were no textbooks on neuroscience at

that

time, at least not that I knew of, whereas now there are 12,000

experiments.

The last Society for Neuroscience conference that I attended was two

years

ago, at which time there were about 5,000 experiments in the same

number of

days. I was able to absorb this amount of information, although with

great

difficulty due to the time involved and due to the increasing

complexity of

the material. At the current conference, I realized that I was no

longer

able to encompass the totality of neuroscience, if indeed I ever had

been.

My confidence in my knowledge of neuroscience previously may have been

somewhat delusional. I was encouraged, however, by the number of

findings

that were presented at this conference that reflect hypotheses that I

had

made in my earlier books about how the brain worked and how it

malfunctioned

in neurosomatic disorders, of which Chronic Fatigue Syndrome is one.

Strangely enough, there were no members of the board of the AACFS at

this

meeting. One would think that these worthies had realized that the

brain

didn't work right in patients with Chronic Fatigue Syndrome, and they

might

want to learn more about why this was so. However, they must have been

overwhelmed with the enormous information overload received at the

AACFS

meeting in Boston two weeks previously, although at the moment I can't

recall any information that was presented that would overload

circuitry.

Reviewing the program and the abstracts, I was reminded of the

song, " Let's

Do the Time Warp Again. " If it had been played at the AACFS, I might

have

been induced to attend, because at least I could have had a little

bit of

fun dancing.

The continued emphasis on cognitive behavioral therapy as perhaps the

only

treatment aside from the checkered performance of Ampligen reminded

me of an

earlier song by Dr. Feelgood and the Interns in 1957 called " You've

Got the

Right String, Baby, But the Wrong Yo-Yo. " Cognitive therapy done

pharmacologically, as I have suggested in the past, is tremendously

more

effective in my practice than cognitive behavioral therapy done by

psychologists. At one time, we had two psychologists doing cognitive

behavioral therapy with my patients, one of whom was my wife, Gail,

and both

had to leave the practice as I became more adept at pharmacologically

manipulating signal-to-noise ratio and perception of saliency of

information

so that it could be gated properly in the patients that I was seeing.

I would like to review for you what I consider to be the most

important

presentations related to neurosomatic disorders at this conference. I

will,

of necessity, omit the vast majority of the experiments that were

presented

since I can hardly allude to 12,000 experiments in this article. I

will be

referring to the pages in the Abstracts of the Society for

Neuroscience of

the 28th Annual Meeting when I discuss the experiments. If you would

like to

obtain the abstracts, which I must wam you are extremely technical

but are

very interesting to me, you can call the Society for Neuroscience, I I

Dupont Cr. N.W., Suite 500, Washington, D.C. 20036. Ask for the

Societyfor

Neuroscience Abstracts Volume 24, Parts I and 11, 1998. 1 would

assume that

in the first four meetings they had not published volumes of

abstracts and

begin with meeting number five. I have had difficulty obtaining

abstracts

before when calling the Society over the phone and so, at this

meeting, I

met the person who is in charge of sending out the abstracts. Her

name is

Marcia Pool. She is a very nice person who wants to make the abstracts

available in an efficient manner. If you call to get the abstracts,

speak to

her.

Let's start with Volume 1. There were usually five or six abstracts

on each

page. I will be mainly focusing on norepinephrine, dopamine, NMDA

receptor

antagonism, GABA, and the regulation of these substances

physiologically and

pharmacologically. Norepinephrine is important in regulating sensory

and

cognitive gating, as is dopaniine and the NMDA receptor. The NMDA

receptor

is one of the receptors for the excitatory amino acid transmitter,

glutamate, and seems to have a central role in much of the

pathophysiology.

The inhibitory neurotransmitter, GABA, which has a significant role in

almost every neuronal activity, is also important. I will also be

alluding

to some of the medications that I use in the treatment of neurosomatic

disorders as they were discussed in the context of the neuroscience

meeting.

Remember that these experiments were primarily done by Ph.D. or M.D.

researchers, who rarely, if ever, see patients but rather focus

primarily on

an extremely narrow aspect of neuroscience. One researcher with whom I

spoke, when I discussed my use of thyrotropin releasing hormone in

the form

of nasal spray and eyedrops, which I will talk about a little bit

later,

almost had an orgasm right there on the convention floor, " My whole

life is

TRW " he exclaimed. TRH is a very small polypeptide molecule that is

cleaved

from precursor polypeptides. This man's whole life was TRH and that

exemplifies the focus of those involved in research. No one that I

spoke

with at this meeting had very much of a conception of how to

integrate his

research with the health and illness of an entire person conversely.

Few

clinical researchers know enough basic science, and the average

practicing

physician knows very little basic science at all.

-Page 353: Prolonged stress may decrease dopamine in the Nucleus

Accumbens

(NAc), an extremely important structure in neurosomatic disorders. It

mediates reward and pleasure. Most of my treatments, when effective,

end up

increasing dopamine, and turn on norepinephrine, especially in the

NAc.

-Page 355: Very early life events can be extremely important in the

predisposition to develop neurosomatic disorders. Newborn rats

separated

from their mothers for 180 minutes on days 2-14 had markedly elevated

norepinephrine (NE) secretion from the locus cerudeus, the main

nucleus in

the brain for NE secretion. After a while, at least in humans, this

elevated

response can become fatigued, can " poop out, " or be dysregulated by

inappropriate perception of the salience of sensory or cognitive

information.

-Page 357: Carbemazepine (Tegretol) and valproic acid (Depakote) do

not

increase dopamine levels in the NAc. They are also not very good

atments for

neurosomatic disorders.

-Page 357: The primary source of doparnine secretion in the areas of

the

brain involved in neurosomatic disorders is called the ventral

tegmental

area (VTA). Dopamine secretion from the VTA to the NAx and prefrontal

cortex

(PFC) is regulated in various ways. One of them is by muscarinic and

nicotinic receptors for acetylcholine (Ach). That's how medications

like

Cognex, Aricept, and nicotine patches can make some patients feel

better,

depending on whether these circuits are working properly (no

response), too

much (worse), or too little (better).

-Page 491: Rats that are bred to have too little GABA in their

dorsomedial

hypothalamus (DMH) appear to develop panic attacks. Almost everywhere

there

is glutamate, the excitatory amino acid (EAA), there is GABA to

balance its

effect by inhibiting it. In this case, infusion of an antagonist to

the

N-methyl- daspartate (NDA) receptor for glutamate prevented panic

attacks

caused by the infusion of lactate. This medication helped to .

restore the

balance. Fibromyalgia patients, but not normals, are much more likely

to

have a lactate-induced panic attack.

-Page 504: Alpha-I agonists (like midodrine or ProAmatine) cause the

secretion of oxytocin. NE is also an Alpha-I agonist. On the

relatively few

occasions when midodrine helps a patient to feel better, I bet

oxytocin

(OCT) is involved.

-Page 507: As measured by H2 150 PET, which can be done rapidly, the

right

prefrontal cortex is critical in maintaining attention to a task when

distractors are present. If your right PFC does not work right (see

Betrayal) you'll be easily distracted, i.e., your concentration will

be

poor.

-Page 528: If you briefly injure a neonatal rat you can increase the

rat's

pain sensitivity for the rest of its life. There is a critical time

window

for this fairly mild injury to produce this effect.

-Page 529: Emeran Mayer has become the leader in irritable bowel

syndrome

(IBS) research. I got to know him and invited him to speak at one of

my

conferences when he was fairly new at this research, and introduced

him to

the role of the brain in 113S. He presented PET scan studies of IBS

patients

and normals. They fail to activate the anterior cingulate cortex

(ACC --

more about this later) and abnormally activate the left dorsolateral

PFC

when anticipating and receiving rectal distention with a balloon. He

followed up this work at the Neuroscience meeting. Moderate non-

noxious

rectal distention caused PFC activation in patients but not normals.

After

sensitzation with repetitive painful balloon distention, the IBS

patients

activated the ACC following nonpainful stimulation, not seen in

normals.

Emeran suggested that normals inhibit pain better from an area of the

brain

stem called the periaqueductal gray (PAG) and so they aren't

sensitized

(develop " hyperalgesia7> I'm not so sure this is the way it works

(higher

centers are involved in regulating the PAG and interpreting painful

visceral

stimuli), but his work is the closest to mine of any researcher. I'm

trying

to feed him as much neuropharmacology and cognitive neuroscience as I

think

he can handle (he's a gastroenterologist). The next steps are for him

to

understand why IBS occurs, and then how to treat it.

-Page 592: 1 have suggested that endothelin in excess can make

neurosomatic

patients feel sick. The effects of endothelin on sensory gating have

not

been studied, but activation of the endothelin A receptor (there are

A & B

regulators which work quite differently) caused reduction in a

potassium

channel response caused by activation of the mu opioid receptor (done

also

by morphine-like drugs). The effect of endothelin was mimicked by

arachidonic acid (AA), produced by the enzyme phospholipase A2

(PLPA2) which

is the main constituent of honey bee venom, one of my treatments,

which

works on a few people. The biochemistry is too complicated to discuss

here,

but AA is an indirect NMDA receptor antagonist, as well as a

stimulator of

dopamine secretion. This experiment suggests that endothelin might be

good

for you, at least in some people.

-Page 601: Amerge (naratriptan) is a migraine headache medicine like

Imitrex

(sumatriptan), Zomig (zolmitriptan), and Maxalt (rizatriptan). What

makes

Amerge different is that it has no side effects or drug interactions

and has

a much higher affinity for the serotonin (5HT1B) receptor, which is

related

to the 5HTIO receptor which they all stimulate. The triptans as a

group

block the release of substance P and calcitonin gene-related peptide

(CGRP),

and can decrease (I have found) the symptoms of cervical spinal

stenosis

when nerve roots and the spinal cord are being compressed, with the

release

of (particularly) CGRP. But Amerge can help more than migraines and

spinal

cord problems. The 5HT IB receptor is crucial for the serotonin

reuptake

inhibitors (SRI) antidepressants to work. If you block it, they are

ineffective. So you can see how directly stimulating the 514TIB

receptor

might be a good thing. It sometimes alleviates fibromyalgia and helps

CFS

patients feel better in general. It also might be the best migraine

medicine

for them, too. It may specifically increase 5HT in the PFC, one of the

places you really want it, working better than SRIs.

-Page 707: If neurosomatic patients are hypervigilant, they should be

more

easily stressed, particularly when they perceive the stressor to be

uncontrollable. And such is the case with many. Blocking the NMDA

receptor

in the dorsal raphe nucleus (DRN), where most of the serotonin in the

brain

is made, ameliorates this sort of stress in rats. If the NMDA

antagonist had

been infused elsewhere (lots of other places) the amelioration would

have

been greater, but the neurotransmitters all work together, like an

orchestra. Some play louder and longer than the others in certain

situations.

-Page 708: When you are stressed, you have neuronal overactivation in

numerous areas of your brain. This overactivation is not good for

your brain

and so it makes more adenosine, an inhibitory neurotransmitter like

GABA to

decrease the activation. Adenosine can make you feel fatigued and

sleepy. It

undoubtedly plays a role in CFS symptoms, particularly when acting in

regions that subserve fear and defensive behavior.

-Page 709: Exercise decreases the amount of norepinephrine in the PFC

of

stressed rats (and people?), one reason for exercise-induced relapse.

There

are others. The complexity of the brain is beyond imagination.

*Page 709: Scalding rats (a stressor) releases endothelin-I (there

are three

kinds) from the hypothalamus into the bloodstream.

-Page 711: This one will be a little complicated. NMDA receptors in

the PFC

constantly ( " tonically " ) inhibit dopamine release. If doparnine

levels in

the PFC are too low, as they probably are in neurosomatic disorders,

then

blocking the NMDA receptors for glutarnate in the PFC will increase

PFC

doparrime, suggesting that glutarnate neurons in the brains of

neurosomatic

patients were hyWfunctionin & since if their PFCs sent more glutamate

to the

VTA, they would get more dopamine back. Interestingly, schizophrenia

has

been postulated to be a hypoglutamateric disorder, but one that

increases

dopamine secretion in the PFC the opposite of what happens in

neurosomatic

disorders, which are more akin to Parkinson's disease, if anything.

-

Page 711: Increasing dopamine in the PFC helps give " working memory "

the

ability to organize multiple tasks and solve problems. I wish I knew

an easy

way to increase PFC doparnine.

-Page 711: Blocking the NMDA receptor with a systemic drug increased

PFC

dopamine (DA), NE, and acetylcholine (Ach). Infusing this drug into

the PFC

increases DA and NE, but not Ach, which is independently regulated.

All

three are involved in increasing attention (focusing), a basic CFS

problem.

-Page 711: Talwin (pentazocine) could be an antidepressant. A related

drug,

igmesine, is.

-Page 712: Lamictal (lamotrigine), one of my favorite medications,

inhibits

the release of glutamate, Thus, it decreases glutamate's effect at

all its

receptors. Rilutek (riluzole) has this effect also.

-Page 746: Repetitive transcranial magnetic stimulation (rTMS) has no

side

effects and might help some patients with CFS. Probes were implanted

in the

hypothalamic paraventricular nucleus and dorsal hippocampus of rats,

which

were then given rTMS. Increases in glutamate, taurine, aspartate,

serine,

and serotonin were noted.

-Page 771: As I have written previously, Marino]

(delta-9-tatrahydrocannabinol) is a very useful agent in neurosomatic

disorders. It stimulates AA release and inhibits glutamate reuptake,

thereby

increasing glutamate levels. Other experiments find different results,

especially that cannabinoids are NMDA antagonists.

-Page 854: Dopamine, acting as the D, receptor (there are at least

five of

them) acts on L-type calcium channels, the same ones that are blocked

by

drugs like Nimotop (nimodipine). D] receptor activation can cause GABA

release and can rapidly change neuron discharge, noise to signal, and

neural

plasticity in the PFC. Calcium channel blockers can " fine tune " these

effects.

-Page 861: Pinolol increases DA and NE, but not 5- HT, in the PFC of

rats.

This effect helps many CFS patients. I don't understand why it

doesn't help

more of them.

-Page 892: Analgesia produced by TENS is blocked by opioid antagonist

naloxone in anliritic rats.

*Page 893: Improgen, an H2 receptor antagonist like Tagamet or Zantac,

relieves pain by a " non-opioid " mechanism. It is an NMDA receptor

antagonist, but these experimenters were apparently unaware of this

fact.

-Page 949: OXT increases enkephalin and hence doparmine levels in the

NAc.

Opioids increase DA in the NAc. That's why some of you have all your

symptoms relieved when you take a Vicodin. I don't know why OXT

doesn't work

in everybody, either.

-Page 1021: The muscarinic Ach receptor couples to PLPA2 to release

AA which

is an L-type calcium channel blocker, like Nimotop.

-Page 1109: Pindolot potentiates SRIs. It is known to be a 5HTIA

antagonist,

but its 5HTIB/10 antagonism might be more important in the

potentiation.

This result is sort of the opposite of what I wrote about Amerge.

-Page 1131: Many patients with FMS have temporomandibular dysfunction

(TMD),

manifested by jaw clenching and teeth grinding. Often, TMD is a

precursor to

FMS. As seen on PET, post-clench jaw pain was associated with

activation of

the thalamus and cingulate gyrus, structures thought to mediate the

increase

in pain.

-Page 1134: The amygdala is a structure involved in fear and other

defensive

and aggressive emotions. It is also involved in the pain relief

produced by

morphine. Infusion of a cannabinoid into the amygdala of rats produced

potent pain relief.

-Page 1135: In a very complex way, patients with FMS pay more

attention to

stimuli they perceive as painful. When a person attends to something

else,

the same stimulus should be perceived as less painful, but FMS

patients have

difficulty switching attention due to their hypervigilance and altered

perception of saliency of sensory and cognitive information. The main

cortical region which processes painful input is called the primary

somatosensory cortex (S I). When normal subjects studied with water

PET

attended to or did not attend to painful stimuli, the activation of S

I

differed, decreasing when they did not pay as much attention to it.

-Page 1160: NE can act as an NMDA receptor antagonist by enhancing the

effect of inhibitory interneurons. The circle has been closed.

-Page 1172: AA increases NMDA-evoked brain blood flow. An agonist in

some

situations, an antagonist in others.

-Page 1193: Brain alpha- I receptor stimulation (by NE or ProAmatine)

is a

protective factor during stress but only at a low range, above which

adverse

effects predominate.

-

Page 1193: Parnate and Nardil work better than Eldepril or

meclobemide in an

animal model of anxiety. I've found this in people, too.

-Page 1198: OXT injected into the PVN stimulates nitric oxide (NO) and

causes penile erection. NMIDA infused into the PVN also causes penile

erection, but by a different mechanism.

-Page 1245: Marinol, acting at the cannabinoid, (CB) receptor,

increased PFC

DA, probably a good thing in many neurosomatic patients.

-Page 1252: The dorsolateral PFC selects, or g=, visual and spatial

information, selecting salient stimuli from irrelevant ones, as shown

by

functional magnetic resonance imaging (fMRI).

-Page 1253: Cannabinoids inhibit wind-up a centrally mediated

increase in

the response of spinal cord dorsal horn neurons to successive stimuli.

Windup can be a precursor to chronic pain conditions.

-Page 1319: Norepinephrine enhances GABAA receptor mediated synaptic

transmission in rat hypothalamic paraventricular neurons. Thus,

norepinephrine can have an inhibitory effect by stimulating gabaergic

interneurons as discussed previously. Norepinephrine also has a direct

effect on the cell membranes by hyperpolarizing them and making them

less

apt to be depolarized and activated by weak stimuli. Thus it can raise

signal - to-noise ratio. This neurophysiologic effect translates in

neural

networks to a patient being less distractible and more able to

concentrate.

-Page 1392: For those patients who have cervical spinal stenosis,

which

could also compress spinal nerve roots exiting from the spinal canal,

CGRP

and substance P are secreted in excess in this situation and enhance

pain.

These substances can be inhibited by one of the triptan drugs that

are used

to treat migraine. CGRP and substance P are also inhibited by

gabapentin,

which acts as well on the thalamus and the anterior cingulate cortex

as

discussed in an article by Ness, et al. in the November, 1998 issue

of the

journal.

-Page 1438: Thyroid status differentially affects behavior of the

depression

prone Wistar Kyoto rat. Wistar Kyoto rats show hyperresponsiveness to

stress

in depression and anxious be havior. They are more likely to become

hypothyroid but are not helped by being given thyroid hormone.

-Page 1430: A precursor to thyrotropin releasing hormone (TRH) has

antidepressant behavioral responses in the rat. TRH itself also

appears to

have antidepressant and antineurosomatic properties in the human

being when

given intravenously in a dose of 500 units and also when given by

nasal

spray in a dose of three units in each nostril. It can also be given

as an

eyedrop.

-Page 1491: An agent like Talwin, called igmesme, increases

extracellular

levels of both NMDA but not 5- HT in the brain. Talwin and igmesme

are sigma

I stimulators or " ligands. " Talwin is thought to have many

neurobehavioral

effects, not just as an antidepressant but also as a potential

antipsychotic.

-Page 1620: There is a pathway from the lumbosacral spinal cord to

the penis

which can regulate penile erection in rats. It is originally

stimulated by

oxytocin at the level of the lumbosacral spinal cord which stimulates

the

secretion of nitric oxide which releases cyclic GMP, a vasodilator

which

causes penile erections. Therefore, there is an oxytocin nitric oxide

cyclic

GMP pathway from the lumbosacral spinal cord to the veins of the

penis that

can cause penile erection. Since oxytocin may be low in patients with

Chronic Fatigue Syndrome, giving oxytocin might be helpful.

-Page 1628: When rats have pain caused by a nerve injury, it is called

neuropathic pain. There are ways to experimentally induce this sort of

injury, and it is fairly well known that the effect of morphine on

such

injuries is somewhat limited, just as it is on central pain. Giving

Marinol

to rats with neuropathic pain decreased the pain significantly. This

pain

relief was independent of the NMDA and the opioid systems.

Furthermore, in a

second experiment on the same page, it was noted that cannabinoids;

suppressed pain processing at the level of the medial thalamus, the

main

switchboard of the brain. They acted there by a non-opioid and non-

NMDA

mechanism.

-Page 1629: Neuropathic pain is relieved by clonidine, a medication

which

stimulates the alpha-2 adrenergic receptor. Clonidine increases the

release

of acetylcholine and nitric oxide at the level of the spinal cord. The

acetylcholine attached to both receptors for the muscarinic and the

nicotinic receptors to elicit nitric oxide production in pain relief.

The

inhibitory neurotransmitter adenosine acting at the Al adenosine

receptor

works as an NMDA receptor antagonist. It therefore can be analgesic

in this

situation and also blocks the release of amino acids that occur

secondarily

to NMDA receptor activation. Amino acids blocked include glutamate,

aspartate, and taurine.

-Page 1680: The activity of 130 neurons in the locus ceruleus of a

monkey

were recorded when the monkey had to make rapid choices between

salient and

non-salient targets. When the monkey performed this task, there was

enhanced

activity in the locus ceruleus. Since the locus ceruleus is the main

nucleus

in the brain that secretes norepinephrine, I would expect that

neurosomatic

patients would perform rather poorly in such tasks.

-Page 1681: Another experiment reports that locus ceruleus neurons are

selectively activated by attentive stimuli suggesting reward

availability as

well as other salient events such as loud noises. The part of this

response

that occurs early when the monkey is performing tasks rapidly that

require

discrimination between cues is thought to indicate enhanced

attentiveness

during this condition and may relect sensory gating which would prime

the

locus ceruleus and many associated structures. Thus, events would be

processed more rapidly. Obviously, performance on this kind of test

would be

impaired in neurosomatic patients.

Another experiment on the same page finds that the right prefrontal

cortex

is necessary to inhibit unattended semantic information. These results

support models suggesting right hemisphere dominance for human

attention. We

have found that there is usually right hemispheric impairment on

brain SPECT

when we examine patients with Chronic Fatigue Syndrome.

-Page 1682: Examines the function of the human anterior cingulate

cortex

which is involved with executive control of cognitive processes,

response

selection, conflict resolution, internal monitoring, anticipation and

preparatory processes, and affective and motivation aspects of

behavior.

Although these terms sound rather technical, they are all aspects of

behaviors that are often impaired in patients with neurosomatic

disorders.

These experimenters found that decisions are computed in the lateral

prefrontal areas and then channeled to the anterior cingulate cortex

for

translation into motor output during which selection between

alternative

responses takes place. On the same page is an experiment which

discusses the

amygdala in the context of fear learning in previously fear

conditioned

rats. This experiment would apply to neurosomatic patients who are

hypervigilant either due to gentic or developmental factors. If the

NMDA

receptors in the amygdala are blocked, new fear learning disappears

rapidly,

i.e., extinction occurs rapidly when the NMDA receptors are blocked.

-Page 1926: An experiment on this page again looks at Wistar Kyoto

rats and

looks for precursors of TRH to understand underlying mechanisms of

depression. In Wistar Kyoto rats, two regions that were examined, the

paraventricular nucleus of the hypothalamus and the bed nucleus of

the stria

terminalis had a lower density of nerve fibers that manufactured

precursors

to TRH than did regular Wistar rats which were not vulnerable to

depression.

On page 1928, an important experiment shows that transforming growth

factor

beta released in the brain by physical exercise causes the sensation

of

fatigue. Rats that became fatigued were found to have elevated levels

of

this substance in their cerebrospinal fluid. Their fatigue was

suppressed by

injecting anti- TGF beta antibody into their cerebrospinal fluid.

Injecting

TGF beta suppressed their activity. These results suggest that either

inhibiting the biosynthetics of TGF beta or blocking its effects in

humans

might be an effective treatment for fatigue along with adenosine

receptor

antagonists that do not cause jitteriness like caffeine does.

There is no published interaction between adenosine and TGF-beta.

Substances

that inhibit the action of TGF-beta are not particularly effective in

alleviating fatigue in my patients. These include Cozaar, intravenous

immunoglobulin, prolactin, and substances that increase it (like

haloperidol), tamoxifen, and corticosteroids. Intravenous

immunoglobulin is

the only agent among these putative TGF blockers that benefits

neurosomatic

patients, and probably by an unrelated mechanism.

Many more experiments were presented at this meeting which I did not

discuss

due to constraints of space and also because of their complexity.

Many of

these relate to bow different circuits or neural networks in the

brain are

regulated, an important concept for understanding neurosomatic

disorders.

Other complex work was related to attentional mechanisms and the

structure

and function of the nucleus accumbens and its interactions with other

structures. These topics, which are vital to understanding the

pathophysiology of neurosomatic disorders, will be addressed in a

forthcoming book of mine which I will be writing with several of my

colleagues who have particular expertise in certain areas that are

relevant

to the present and the future understanding and treatment of

neurosomatic

disorders.

----------------------------------------------------------------------

------

----

ABBREVIATIONS USED

5HT = serotonin, or 5-hydroxytryptamine AA = arachidonic acid

ACC anterior cingulate cortex Ach acetylcholine

CB = cannabinoid

CGRP = calcitonin gene-related peptide DA = doparnine

DMH dorsomedial hypothalamus DRN dorsal raphe nucleus

EAA excitatory amino acid

GABA = gamma aminobutyric acid NAc = nucleus accumbens

NE = norepinephrine

NNMA = N-methyl-d-aspartate OXT = oxytocin

PAG = periaqueductal gray PFC = prefrontal cortex

PLPA2 = phospholipase A2

PVN = paraventricular nucleus of hypothalamus SRI = serotonin reuptake

inhibitor

TGF-beta = transforming growth factor beta TRH = thyrotropin-releasing

hormone

VTA = ventral tegmental area

http://www.drjgoldstein.com/frames/04apptointments.html

Leni

bc mailto:las@g...

Replies Author Date

489 Re: Goldstein summary re: Neuroscience/CFS Hud Ramelan Fri

May 19, 2000 7:11am

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