Clueless about the brain and placebos :-(

[Guest poetry_chick]

Hi everybody i'm new to this forum and this site but i'm in desperate need of help. I recently got a Psychiatry project on placebos and how they affect the brain. I started writing the paper but i sounded like a Psychology paper. I mean I know what placebos are and what they do but how, where, when, why?

The hows and wheres are the most important. How does you brain convince you and makes you act on something that does nothing (and i know it's not just will power). And where does it take place in the brain.

I usually dont ask for help with science projects i mostly cheak it on the internet or experiment myself but i don tthink my mom would allow me to experiment with my brain so i'm forced to rely to the internetand it;s mystical ways.

So please everybody i really need help. I know nothing on why, how and where, Placebos scientific effect on the brain and how the brain responds. Could some of you intellectually advanced people help out a girl clueless about the brain and placebos?

[fafalone]

Please don't post the same thing over and over again. Thanks.

[blike]

I think Glider would be most appropriate to answer this question. A lot of placebo's work because our expectations of something effect how we perceive it. In other words, I expect that when I take a a certain medication that it will have a certain effect on my body. I'll look into it a bit more tomorrow and give a better response.

[Radical Edward]

placebos are a good way of making people stop focussing on the illness and leave the doctor alone.

[Glider]

Originally posted by poetry_chick

Hi everybody i'm new to this forum and this site but i'm in desperate need of help. I recently got a Psychiatry project on placebos and how they affect the brain. I started writing the paper but i sounded like a Psychology paper.

1) In what way is that a bad thing? 2) What exactly is the difference?

I mean I know what placebos are and what they do but how, where, when, why?

The hows and wheres are the most important. How does you brain convince you and makes you act on something that does nothing (and i know it's not just will power). And where does it take place in the brain?

Blike is absolutely right. Placebos depend on individual expectancies.

 

First of all, placebos don't work on everything. For example, somebody suffering a bacterial infection will show very little improvement if given a placebo rather than an antibiotic (although they might 'feel' better for a little while), and you couldn't expect to prevent a diabetic from entering a hypoglycemic coma by giving them a placebo. Placebos exert their influence on symptoms that depend on the psychology of an individual, e.g. conditions such as pain, stress, mild depression, anxiety, insomnia etc..

 

HOW

The repeated laying down of associations between action and outcome or stimulus and response produces long term neural changes (learning, in essence). For example, the physiologist Ivan Pavlov noticed that his dogs began to salivate (unconditioned response) before they were given food (unconditioned stimulus). He paired the unconditioned stimulus (food) with a non-related stimulus (bell) in order to elicit the unconditioned response (salivation). After a while the dogs learned that the bell meant food and Pavlov found that the conditioned stimulus (bell) on its own would elicit (what had become) the conditioned response (salivation). This is simple classical conditioning.

 

Related to this is 'Skinnerian', or operant conditioning. This is where an organism forms a long-term association between its actions and the outcome. Skinner placed a cat in (what is now known as ) a Skinner box. This is a box which locks and only opens if a lever is pressed from the inside. The cat made random attempts to escape and eventually pressed the lever. The box opened. On subsequent trial, the cat took less and less time to press the lever as the association between its action and the result was reinforced.

 

Humans are subject to both forms of learning. If you are hungry and you smell food, you will begin to salivate and produce gastric acids (a classically conditioned physiological response to psychological associations between the smell and the reality of food). If we have a headache, we take a paracetomol tablet, the pain goes away. We do this often throughout our lives, and so we build an association between taking the tablet and the removal of a negative state (pain). This is operant conditioning: negative reinforcement.

 

If we are in pain, and we are given a tablet which we are told is paracetomol (or some other effective analgesic), its presence, and the action of taking it will induce physiological changes that we have been conditioned to expect. Our expectancies and short-term hypotheses concerning the situation and probable outcomes will be dependent upon these conditioned associations. Pain is a psychological experience and significant componants of pain are anxiety, frustration and general negative affect (a negative emotional state). These are responsible for the 'suffering' associated with a pain state. The belief that we have taken an effective analgesic will result in a reduction in anxiety and frustration, and an elevation of affect. In essence, although the placebo has no effect on the cause of the pain, it still significantly reduces the suffering associated with it. Moreover, a large proportion of headaches (for example) are caused by muscular tension in the neck and shoulder regions, caused by stress, or simply bad posture. The above effects of taking the placebo (reduction in pain-related anxiety, frustration and elevation of affect) will result in our relaxing. In this case, the headache will probably go as we will have reduced the underlying cause.

 

WHERE

Broadly, for pain there are the lateral and medial pain systems. The lateral involves the ascending spinothalamic tract (extralemniscal system) > lateral thalamus > somatosensory cortex. This is responsible for the sensory-discriminatory component of pain, allowing us to localise pain (where it is) and evaluate its intensity and qualities (how bad and is it burning, shooting. dull, stabbing etc.?).

 

The parts affected by the placebo are in the medial pain system, which is involved in the affective-motivational component of pain. This includes the spinothalamic tract, the medial thalamus, the anterior cingulate gyrus, the frontal cortex, the insula and the periaqueductal grey area of the brainstem. Many of these structures are also included in the circuit of Papez, which is involved in emotional processing. This consists of: The hippocampal formation, mamilliary body, anterior thalamic nuclei, the cingulate cortex, the pre-frontal and association cortices, the hippocampus and underlying gyri and the amygdalae.

 

Several of these structures are responsible for the detection and pre-conscious processing of salient, valenced environmental information, i.e. they respond particularly to novel stimuli and assess it for safety or danger. In other words, they check all incoming information to see whether it is good (food, sex, etc.) or bad (constitutes the possibility of harm). Many of the schema (the things which incoming stimuli are compared to) are hard wired (e.g. primates react the same to a length of hosepipe in the grass, as they do to a snake). However, many are learned. The amygdala has been shown to be an area of neural plasticity, and forms the associations between stimulus and outcome (labels stimuli for valence (good or bad) depending on what results on exposure to it). The hippocampus is also associated with memory. The anterior cingulate cortex (ACC) is responsible for assessing valenced information and selecting our response (basic motivation to approach or avoid the stimulus) to it.

 

So, if we are in pain, we become particularly sensitive to pain related environmental stimuli. If we perceive a possble means of alleviating the pain (an analgesic), this is flagged by the amygdala and the ACC. The ACC and reticular activating system makes us orient towards the stimulus, and the ACC and pre-frontal and frontal cortices match up the stimulus with previously learned outcomes (with help of previous labelling from the amygdala), and the basic motivation to approach that stimulus is engaged by the ACC. When we do approach (and take) that stimulus, we are rewarded (by the activity of dopaminergic neurones in the 'reward centres' or the brain). The successful fulfillment of the approach motivation results in an elevation of affect. The change in our emotional state to a more positive one, results in a change in the activity of the medial pain system, and greater feedback to the periaqueductal grey area (PAG), which is a significant componant of central pain control. This projects ventrally to the Raphe nuclei (particularly the Nucleus Locus Coeruleus). The descending raphespinal pathways terminate in the laminae of the dorsal horn of the spinal cord (the substansia gelatinosa) where it provides inhibitory feedback to the ascending spinothalamic projection neurons.

 

So, the effect of a placebo with respect to pain at least, is an elevation of affective state which is generated mainly in limbic structures, and has a positive psychological effect on the 'suffering' associated with pain, but also increased inhibitory feedback via central pain control systems (PAG & locus coeruleus) resulting from changes in the acitivity of the same limbic structures.

 

WHEN

Whenever we take a placebo.

 

WHY

Why not?

 

Three points to remember:

 

1) Placebos can only work if the original association between the stimulus and its effect has been laid down, i.e. a placebo analgesic wouldn't have any effect on somebody who has never seen a painkiller before, unless you could convince them absolutley that what you were giving them will kill the pain. Like Blike said, the effect depends on the expectancies of the individual.

 

2) Although this example focusses on the placebo effect on pain, the underlying principles of the placebo effect remain the same.

 

3) I ain't no psychiatrist.

 

:psi:

[contradiction]

i read somewhere that they gave suger pills to half of these people and 20mg morphine to the other half . a certain amount of the suger pill people experienced pain relief, blah blah..

but... the interesting part was that they gave everyone NAXALONE (at a later date, in the same pill, with suger, or morphine) ........ ok naxalone is an opiate antagonist, so, it blocks the effects of morphine and other opiate painkillers.

 

as one would expect, the people taking the morphine pill with naxalone in it no longer experienced relief.

 

the significant part is that the people taking the suger pill with naxalone no longer experienced relief either! (at the beginning everyone was told they were getting morphine.)

so, this says that placebo is accually a real physical chemical reaction in the brain, ...some chemical is produced that binds to opiate recepters, and is therfore blocked.

 

so this takes the concept of placebo effect from psychological, to physiological. mind to matter....... which are the same thing anyhow.

[fafalone]

I wonder if there's any studies where people were given a real dose of something but experienced nothing when they really expected some sort of result.

[Glider]

Originally posted by contradiction

the significant part is that the people taking the suger pill with naxalone no longer experienced relief either! (at the beginning everyone was told they were getting morphine.) so, this says that placebo is accually a real physical chemical reaction in the brain, ...some chemical is produced that binds to opiate recepters, and is therfore blocked. so this takes the concept of placebo effect from psychological, to physiological. mind to matter....... which are the same thing anyhow.

This is quite true. People still talk of "psychological reactions" as separate and distinct from "physical reactions". But if you accept that there isn't a thought or a feeling that doesn't have its origins in activity in some region of the brain, then the distinction becomes less clear.

 

In the example of naloxone blocking the (analgesic) placebo effect, as I said yesterday:

If we are in pain, and we are given a tablet which we are told is paracetomol (or some other effective analgesic), its presence, and the action of taking it will induce physiological changes that we have been conditioned to expect.

Among these changes is an increase in 5-HT which is associated with elevated affect (and is thought to be one of the transmitters responsible for the inhibition of spinothalamic projection neurons in the dorsal horn via descending raphespinal projections from the periaqueductal grey). Also, activity of dopaminergic neurons in the 'reward' centres and the release of endogenous opiates (endorphines).

 

The important thing here is the centres that are responsible for bringing about these changes:

The parts affected by the placebo are in the medial pain system, which is involved in the affective-motivational component of pain. This includes the spinothalamic tract, the medial thalamus, the anterior cingulate gyrus, the frontal cortex, the insula and the periaqueductal grey area of the brainstem. Many of these structures are also included in the circuit of Papez, which is involved in emotional processing. This consists of: The hippocampal formation, mamilliary body, anterior thalamic nuclei, the cingulate cortex, the pre-frontal and association cortices, the hippocampus and underlying gyri and the amygdalae.

Of these (and among others), the ACC, the amygdala and the thalamus are rich in opiate receptors

(Chen, 2001).

 

The ACC in particular has been implicated in the central control of pain (Jones, 1997), and surgical lesioning of particular areas of the ACC is sometimes used in the treatment of intractable pain conditions. However, the introduction of naloxone into this system would inhibit the activity of the central control mechanism (i.e. inhibit the actions of the action of the ACC and descending fibres to the medial thalamus and the PAG), and so would prevent central inhibition of pain.

 

So it's true, the placebo effect is a 'genuine' effect, and the results of experiments showing inhibition of the placebo effect should really only surprise those who consider "psychological effects" to be synonymous with "imagined effects".

 

References

 

Chen, A. C. N. (2001). New perspectives in EEG/MEG brain mapping and PET/fMRI neuroimaging of human pain. International Journal of Psychophysiology, 42 (2), 53-65.

 

Jones, A. K. P. (1997). Pain, its perception, and pain imaging. IASP Newsletter Technical Corner, 1-5.