DRUG THERAPY OF BRUXISM
AS MODULATION OF STRESS ANSWERS.
Renato COCCHI MD,
neurologist and medical psychologist3
Summary
When
not produced bu occlusal factors, bruxism is strictly related to stress, being
an unspecific answer of it. Following decennial experiences in drug treatment
of bruxism by modulation of stress responses in Down’s syndrome, PDD and MR
children, possible neuropathological mechanisms linking stress and involuntary
masseter muscle activation are discussed. Modulation of stress responses by
drugs are explained in general and in particular for bruxism, with the
rationale of the drugs use.
Key words: Bruxism; stress; drug therapy.
Drug modulation of stress reactions
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Before my trial to explain the link between
stress and bruxism, I need to give a warning. My knowledge of bruxism is
closely limited to bruxism in mentally retarded, in Down's syndrome persons and
in PDD subjects, because asa neurologist and a medical psychologist I have
special interest in this kind of patients.
So I could have a different approach and
language of dentists. I hope I shall make myself understood as well.
Defining
bruxism
This is the definition of bruxism I shall have
in mind for this paper.
Bruxism is a parafunctional behaviour of the
temporo-mandibular joint getting to teeth grinding or teeth clenching. This
second phenomenon is not widely accepted as bruxism.
According to Palla, 1989, bruxism belongs to
"the Temporo-Mandibular Joint (TMJ) pain and noise", one key symptom
out of 3 for the diagnosis of somato-gnatic myoarthropathy.
Bruxism does not work out for all "the
TMJ pain and noise" but I shall strictly refer to bruxism.
As for the occlusal tooth contact as the
result of this Temporo-mandibular Joint Diseases (TJD) we can have:
- teeth grinding, when teeth are rubbing
together, mandibular against maxillary teeth, with a particular and
unmistakable noise.
- teeth clenching, when mandibular teeth are
strongly pressing against maxillary teeth.
- teeth chattering, when mandibular teeth
are beating against maxillary teeth about 1-4 times per second.
I do not think my problem to write about
damages that can follow these three phenomena. Dentists knows very well them
Are teeth grinding, teeth clenching and
teeth chattering three aspects of the same TJD or three different phenomena? In
my opinion they do not belong to the same TJD, although all three are symptoms
of TJDs.
Cold, fear and some types of infective fever
(eg. Bacterial pneumonia fever) induce only teeth chattering.
Clostridium tetani induces only teeth
clenching as it happens in the 1st phase of the epileptic Grand Mal seizure
(the tonic phase).
As we reported (Cocchi and Lamma, 1987), we
only found teeth grinding in Down's syndrome children.
Perhaps dentistry professionals can put
forward many other examples, part of which also denying my simplistic
categorization, but I think the above exaples as useful to explain why I have
just written.
Incidence
and etiology
There is not full agreement on the incidence
of bruxism. A recent review made by Belgian authors states the mean prevalence
of bruxism as about 20% in young and adult populations (De Meyer and De Boever,
1997).
This shows the extent of this behaviour and
its importance from the dentistry point of view. Bruxism in mentally disables
has a higher rate as reported for institutionalized adults by Richmond et al.,
1984. As for us, from a consecutive unselected series of 366 Down's syndrome
children (mean age 5 years and 10 months) dr Lamma and I (1987) found a
prevalence of 41.80%.
This growing sub-population has this trouble
among many others and need careful attention by specialized professionals in
this field too.
The symptoms more frequently associated with
bruxism are, in rate order: Muscle-stiffness, muscle-pain, limitation of mouth
opening, TMJ-internal derangements, toothwear. No one of these symptoms is
peculiar of bruxism, but they can be found in other somato-gnatic
myoarthropathies as reported by Palla, 1989.
As for the etiology of bruxism, there was a
long controversy on this topic. Psychological stress was asserted as the main
causal factor according to experimental data, but it does not fully explain
sleep bruxism (Morse, 1982). Personality features have been often found and
they always fitted the so-called "neurotic personality" whit strong
genetic bases.
Palla, 1989, by referring to all
somato-gnatic myoarhropathies, points up stress factors, the only ones with
experimental evidence.
As for bruxism in Down children, in 1988 dr
Lamma and I underlined stress because an ex-juvantibus drug therapy.
Before I am going forward, I must say that I believe in stress as the causal
factor of bruxism. But I have to remember you that psychological stress is only
one type of stress, and perhaps not the more important.
Stress
and bruxism
By speaking of stress and stress reactions
(or answers) in general we can note two kind of reaction to stress: stress with
a lack of energy and stress with an excess of energy.. Between these two, I
shall refer to stress reactions with an excess of energy, because they are the
only ones pertinent to bruxism.
Now I need to define the concept of stress.
Although I do not fully agree, this is the
most authoritative stress definition:
" .... it generally refers to physical
or psychological alterations capable of disrupting homeostasis." (Cullinan
et al., 1995).
Waiting for a more precise one, in 1996 I
proposed the following as an operational definition. We can term stress a set
of relations linking external or internal stressors of physical, chemical,
biological / metabolic and psychological / social origin, to nonspecific
reactions of a living organism. These reactions come out from the modification
of homeostasis made by the stressor or stressors, and act as a common final
pathway.
As you can see psychological stressors are
only one part among all stressors, although surely the best investigated.
Stress reactions can come out from external
stressors, or internal stressors or
both. An illness can act per se as an internal stressor (Loo and Loo,
1986). The more frequent of internal stressor is the falling of proge-sterone
just before menses in fertile women. Its stress reanctions constitutes the
premenstrual syndrome without any progesterone-linked specific symptom (Cocchi,
1998; Mortola 1992; Mortola, 1997)
Bruxism then can be due to internal stress
reactions to an illness itself, and I think this is the case of Down’s
syndrome, or PDD, or other Mental Retardation, as for my long lasting
experience.
How stress can produce bruxism is a big
question and I cannot give you a sure answer in this paper. I shall only put
forward two hypotheses, but I don't know what is the best one, of course if
there is a best one.
Now at least three questions arise:
How stress is working till to drive at
bruxism?
All stressed people has bruxism as a
symptom of stress?
Why bruxism is declining with age?
One should agree with me by saying that the
second question has a negative answer. Not all stressed people react with
bruxism. This is a fact of common evidence. To explain it we surely can
remember the idea of "the target organ" as the privileged body place
where stress reactions apply themselves in first beating.
Among other possibilities, some people react
to stress with bruxism. Is it the TMJ the only body district where these people
react to stress? I cannot give you a sound answer to that question because I am
lacking experience in normal individuals. As for mentally retarded I could
assert that it is not so, as dr Lamma and I investigated recently (Cocchi and
Lamma, 1999).
About the third question - Why bruxism is
declining with age - new difficulties come out. To say declining with age does
not mean that bruxism disappears with age. Old people without any tooth, or
with amovible dental prosthesis are reported as bruxing with gums.
Ageing is known as a state of reduced
ability to fight stress (You, 1996; Pike et al., 1997; Friedman e Irwin, 1997;
as for cows, see Garcia-Belenguer et al., 1996).
But reduced prevalence means reduced stress,
while ageing is a stressor. Are we faced to different type of stress, -
bruxism-promoting stress, and bruxism non-promoting stress - or age could break
the link between stress and bruxism in some people?
If ageing could drive to stress with a lack
of energy, the contradiction should have its solution, but I did not read any
research on this topic.
Exploring
possible pathogenesis of bruxism: Brain neuronal links
The first question needs now to be
discussed.
Which brain conditions under stress can
induce bruxism in receptive persons?
As I said above we can forward two
hypotheses. The following is the simplest. Stress usually produces un unbalance
of trigeminal nuclei, mainly of the nucleus motorius nervi trigemini with an
overstimulation of it. This stimulation acts directly on muscle masseter ( and
on muscle temporalis, in a reduced way) so inducing bruxism.
Of course I do not have any confirmation of
this hypothesis, and I can think about it only by analogy.
In many Down's syndrome children with
convergent squint the antistress therapy I prescribed could correct their
squint (Cocchi, 1991).
I must remember you that oculomotorii nuclei
are located in midbrain and pons and in this type of squint is due to a
paralysis of muscle rectus lateralis following an an abnormal function (low
function) of the nucleus nervi abducenti. The contrary hypothesis can also be
forwarded: An overfunction of the muscle rectus medialis following an
hyperstimulation of the related nucleus nervi adducenti can also be
hypothesized. In bruxism there is not a low function but an excess stimulation
of nucleus motorius nervi trigemini, and this fact seems closer to the
hypothesis of hyperstimulation for convergent squint.
On the other hand, I must say that the same
antistress drug therapy reduces or make the disappearance of both bruxism and
squint in Down's children.
The second hypothesis is very complicated.
Better than limbic system, stress increased hypothalamus glutamate excites in
its turn vagal nuclei (Dorsalis, Tractus solitarius, Ambiguus). But afferent
fibres from nervus glosso-pharyngeus and nervus vagus give collaterals to
nucleus spinalis nervi trigemini. The same makes an afferent fibre of the
nervus facialis (Lippert, 1998) The nucleus motorius nervi trigemini will be
over aroused by the normal coordination between sensorial and motoric nuclei of
the same nerve. The recently reported anti-bruxism effect of propranolol, a
beta blocker (Sioeholm et al, 1996; Amir et al, 1997), the pro-bruxism effect
of apomorphine and indifferent (Gomez et al 1998) or pro-bruxism effect of
haloperidol (Amir et al., 1997) suggest that dopamine can be involved per se or
as noradrenalin and adrenaline precursor in that behaviour.
Exploring
possible pathogenesis of bruxism: Peripheral mechanisms added.
As for ACh mechanisms during stress, I need
to point up the possibility of an increased synthesis of peripheral ACh
following a reduced turnover of brain ACh and its increased efflux of choline,
its precursor, from the brain (see further). Greater availability of ACh in
masseter muscle could be responsible of spontaneous fasciculations you can see
in many "neurotic" individuals in TMJ rest conditions. In addition,
more ACh increases muscle tone and muscle strength by a prolonged action on the
neuromuscular end-plate. I am not sure about it, but I think that the habit of
chewing bubble gum by many individuals could be a consummatory behaviour to
reduce this ACh excess. If so, people with increased peripheral ACh during
sleep could need to chew the bubble gum since the awakening.
Exploring
possible pathogenesis of bruxism: Other brain mechanisms
Night bruxism comes out from the increased
action of glutamate, because its reduced turnover when sensory afferent nerves
using glutamate are at rest during sleep.
Night bruxism can appear after sleep onset
18 minutes. Most of bruxism occurred in stage 2 sleep and Rem sleep and was
related to a mechanism of developing arousal (Bader et al, 1997)
Neurotransmitters involved in bruxism are in
part the same involved in stress: GABA as the first responder to stress by
reducing A inhibition; again GABA by increasing B inhibition and by that way it
inhibits the turnover of ACh, Dopamine e Serotonin. This last brain monoamine
seems not directly involved in bruxism.
Glutamate increases because its reduced
transformation into GABA following a feedback mechanism. According to
propranolol trials noradrenaline and adrenalin seem also involved.
Prelude
to drug therapy: 1. Modulation of stress reactions by drugs.
As you have read, there at least two ways to
fight bruxism by drugs: the propranolol therapy for sleep bruxism, and the
antistress therapy for night and day bruxism. They differ because propranolol
therapy desensitises the final or one of final receptors (the beta receptor of
adrenalin). Antistress therapy aims to increase stress thresholds and by this
way to reduce bruxism as a stress symptom.
In first case your referent is bruxism, in
the second case it is stress and you need diagnosing stress in a careful way.
To understand modulation by drugs of stress
reactions we need to have a very short and rough sum up of some neurochemical
mechanisms involved in reactions to chronic stress of a human body:
1. Direct acting on type A gabaergic
receptors; these modify their conformation and by this way reduce type A
gabaergic inhibition (Horger and Roth, 1995);
2. Reduced need of GABA for type A gabaergic
inhibition means more GABA into the synaptic cleft (Cocchi, Patrucco, Zerbi,
1987);
3. Increased type B gabaergic inhibition
that, in its turn, inhibits brain acetylcholine (Scatton and Bartholini, 1980),
serotonin (Scatton et al., 1986);
As for acetylcholine, its reduced turnover
seems to drive to a reduced brain synthesis, lowering blood-brain barrier
transport of choline by reduced high-affinity uptake (Hope, 1979). Although a
low-affinity uptake starts working (Hope, 1979) there is more choline supply
for the synthesis of peripheral acetylcholine.
Moreover a choline efflux from the brain has
been found in old people and in reduced diet (Klein, Koppen and Loffelholz,
1990; Klein et al., 1992), both stress factors, according to the present point
of view.
The supposed increasing of peripheral ACh due
to an increased synthesis during stress parallels many clinical findings and it
was found into the vagal district (Hata et al., 1986; Kita et al., 1986).
The reduced brain turnover of ACh ( with
less need of its precursor, the choline) seems to have its causal factor by an
increased B Gabaergic inhibition on ACh (Williford et al, 1981; Goto et al.,
1985).
This could account, at least in part, for
increased strength of parasympathetic / vagal responses, elicited from the
brain by direct stimulation of type B gabaergic receptors (Williford et al,
1981; Goto et al., 1985).
4. Compensatory incretion of peripheral
adrenalin (Zigmond, Finlay and Sved, 1995), and glycocorticoids (Sorg and
Kalivas, 1995), with immune-suppressive action (Dhabhar et al., 1996; Haessig
et al., 1996; Dantzer, 1997; Friedman and Irwin, 1997).
5. More GABA into the synaptic cleft
backwards reduces GAD activities (Baxter, 1976, Loescher 1980) with reduced
transformation of glutamate into GABA.
6. Excess of glutamate, besides being excitatory
and eventually neurotoxic (Rothman and Olney, 1986), seems to increase
mesoprefrontal dopamine (Horger and Roth, 1995). Although controversial, the
same appears to happen for noradrenalin activity in Locus Coeruleus, the main
brain site for this neurotransmitter (Zigmond, Finlay and Sved, 1995).
The glutamate excitement of cells of some
hypothalamic nuclei, namely the dorso-medialis and the paraventricularis
stimulates the answers of the nucleus dorsalis vagi and nucleus tractus
solitarius, with an increase of the vagal outflow (Kunos e Varga, 1995; Yoneda
e Tache', 1995; Brann, 1995; Pluzhnichenko, 1997).
7. The serotonin reduced turnover, besides a
depressed mood, can inhibit the serotoninergic antipain answer starting from
Rafe Magnus.
Of course, this is only a very simplistic
general frame, but it is a good point to start.
2.
The choice of drugs to modulate stress responses.
There is a growing interest in drug
treatment of stress (Davidson, 1997)
Drug modulation of stress responses mainly
acts on GABA and related brain mechanisms and its results have a direct effect
on the EEG. EEG mapping seems a tool to point the time course out, as I did in
old people with intellectual disturbs (Cocchi, 1996) According to what I have
just said, the main focal points to act by drugs are:
1. Basic interventions:
- increase type A gabaergic inhibition;
- decrease type B gabaergic inhibition;
- Increase the GAD action.
By themselves those induce also:
- decreasing cortisol incretion and the
peripheral adrenergic compensation, by decreased activation of the
hypothalamus-hypophysis-cortico-suprarenal axis (Buckingham, 1998; Schedlowski
and Schmidt, 1996);
- decreasing of possible glutamate excess by
an increased transformation of it into GABA.
- reduction of type B Gabaergic
inhibition of Ach and serotonin turnovers.
2. Other interventions related to the
presence of specific symptoms:
- increase brain acetylcholine
synthesis, if in need;
- decrease both vagal outflow and increased
strength of vagal responses.
- increase of brain serotonin, in order
to feed up the serotoninergic antipain answer;
- acting on dopamine, but this last
intervention could ask the help of expert specialists able to evaluate the
direction of current dopaminergic symptoms.
Being a cascade events having its starting
point on reduced type A GABAergic inhibition, from a theoretical point of view
one could use only one drug, a benzodiazepine (Schoch et al., 1985). This is
not the best way to afford it, because we shall need high dosages, which in
turns produce side effects (eg.: drowsiness and muscle relaxation). They could
also induce a new share of stress reactions (chemical stress due to the foreign
nature of drugs, according to Antelman, 1988; Cocchi 1998; Covelli et al.,
1998).
As I did, mainly in Down children and in
autistic children (Cocchi, 1996), we can do better using:
- A low dose benzodiazepine, to act on type
A GABAergic receptors (eg.: clobazam 10-20 mg; diazepam 3-12 mg: daily doses).
Benzodiazepines, as antistress drugs reduce the cortisol incretion (Bruni et
al. 1980; Viukari, 1983).
- a brain Ca-agonist (nimodipine, verapamil
or, better, carbamazepine (Crowder and Bradford, 1987) to reduce type B
GABAergic inhibition (Liron et al., 1985; Borman, 1988). As for carbamazepine,
200-400 mg/daily could be the mean daily regimen). The decreasing of type B
GABAergic inhibition on brain ACh could stop or at least cut down the efflux of
choline from the brain.
- pyridoxine (150 mg daily), acting as
cofactor of all decarboxylases, GAD inclusive;
- if in need, pyritinol (100 mg/daily),
a good increaser of brain ACh synthesis (Blusztajn and Martin, 1988; Greiner,
Haase and Seifried, 1988; Toledano and Bentura, 1994); An increased synthesis
of brain Ach drives the synthesis of peripheral Ach to normal, by reducing the
peripheral choline supply via an increased blood-brain barrier uptake of the
choline.
- If the case, a low dose antidepressant
drug has to be added.
Nearly always serotoninergic mechanisms
need to be balanced too. In this case use a low doses antidepressant drug, able
to potentiate the antipain serotoninergic mechanism descending from the Rafe.
You can use antidepressant drugs, from tricyclics to SSRIs. You can increase
their action by increasing the brain serotonin synthesis with the direct
precursor, 5-hydroxytriptophan. Vit.B6, as the decarboxylase catalyst for the
transformation of 5HTP into serotonin, has already its place in this regimen.
- if in need, according to current symptoms,
you can act on the dopamine for a short time by using or an antipyshotic
(haloperidol or perphenazine at very low doses) or with the pro-do-paminergic
amantadine.
- the whole reduction of stress responses by
reducing the cortisol incretion, fights the reduction of cell-mediated immunity
(Dhabar et al., 1996; Haessig et al., 1996; Cocchi, 1999).
- the increasing synthesis of GABA
reduces the glutamate excess and by this way reduces the endogenous opiates
incretion (Stout, Kilts and Nemeroff, 1995). Less hypothalamic glutamate
decreases the vagal nuclei stimulation, which are drivers of all the vagal
parasympathetic answers increasing in stress conditions with even an excess of
energy (Brann, 1995).
Evidently a multi-drugs therapy like this
does not easily fill a standard protocol. This because of the individual features
of stress responses, either constitutional either linked to the peculiar
biological moment of that body.
On the other hand our brain does non work by
independent relationships of causes and effects, and the poor efficacy in the
long run of recent and expensive drugs used as monotherapy in Alzheimer disease
has a cogent need. We cannot act on a sole non core point of a multiavariable
system.
But the first three drugs (a benzodiazepine,
a CA++ antagonist, and the vit. B6) are useful in most cases and can be adapted
to every patient.
With these drugs too we need avoiding that
prescribed doses higher than the individual tolerance become in their turn
biochemical stressors (Cocchi, 1998)
Drug
therapy of bruxism
A part from propranolol, a very new
suggestion of which I do not own any experience, I am working on drug therapies
on stress since at least 20 years (Cocchi, 1981; Cocchi, 1989, 1990, 1990a;
1990b; 1991a; 1991b; 1991; 1991; 1991, 1992, 1994, 1997, 1998; Cocchi e Favuto,
1993)The aspecific drug therapy on stress reduces bruxism; this was my starting
point.
In adults pyridoxine, carbamazepine and a
benzodiazepine are the best basic medication. Other drugs can be added
according to specific current symptoms.
In Down children glutamine, pyridoxine and a
benzodiazepine showed good results, but in some cases carbamazepine had to be
added.
As for L-glutamine, it is the precursor of
GABA via l-glutamic acid and its importance is growing awareness in last years
(Laake et al., 1995; Shupliakov et al., 1997).
Conclusions
Bruxism is a non specific symptom of stress,
because it could have occlusal factors and because not all stressed people have
this symptom. When local factors have been excluded, stress origin of bruxism
must be considered and a proper drug therapy could be prescribed, acting on
GABA and related neurochemical mechanisms.
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Paper printed on It. J. Intellect. Impair. 1999, 12: 3-12
Author’s address: dr Renato
Cocchi, via Rabbeno, 3
42100 Reggio Emilia (Italy)
renatococchi@libero.it
Drug modulation of stress reactions
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