ArticlePDF Available

Low-dose oxytocin stops unexplained 'burning' pain in fibromyalgia: A case report

Authors:

Abstract and Figures

Pain can take many forms, and finding an adequate treatment is sometimes difficult. In Fibromyalgia, the brain or nerves are usually seen as the culprit of hyperalgesia. The role of the 'hypothalamic osmostat' has been overlooked. We report here a pain effect relieved by the hormone oxytocin (OT) and better baseline dehydration. Case presentation A Caucasian 53 year-old menopausal female with fibromyalgia presented with unexplained 'burning' pain, among others. Endocrine, nervous, and immune investigations revealed nothing that could explain it. Her medical history included a sensitive nervous system and an untreated lifelong low-grade dehydration. The triggering factor was traced back to a one-month course of bio-identical progesterone that had worsened the dehydration. The hypothalamus is involved in various ways in symptoms of fibromyalgia and stress sensitivity, but also in the water balance regulated by the hypothalamic osmostat, so attention turned to the hormone oxytocin. OT is seldom used in therapeutic setting, except in obstetric care. Current research on oxytocin tends to focus on its central role in the brain, using large doses, and on its interaction with vasopressin, affecting reproductive and social behaviour. A more basic role for oxytocin in the hypothalamic osmostat has become apparent through systemic effects in this patient. A two-week intranasal treatment with low-dose OT proved effective in resolving the burning pain, but also resulted in a general improvement, including of hydration. This report discusses sensitivity, similarity with critical conditions, dose-related and baffling 'inverted' effects. The unexpected general improvement described here offers benefit for vital functions and other 'basic' needs, as well as the capacity for physical self-care and compliance with a treatment. The protocol used could be a new avenue to better match treatments to the needs of 'sensitive' patients. - Please see also ADDITIONAL FILES: 1- What is known about OT (2010) 2- Theoretical reflections about OT
Content may be subject to copyright.
1
Low-dose oxytocin stops unexplained
‘burning’ pain in fibromyalgia: a case report
M. Bouchon*
Corresponding author email*: mbouchon@ozemail.com.au
Abstract
Pain can take many forms, and finding an adequate treatment is sometimes difficult. In
Fibromyalgia, the brain or nerves are usually seen as the culprit of hyperalgesia. The role of
the 'hypothalamic osmostat' has been overlooked. We report here a pain effect relieved by
the hormone oxytocin (OT) and better baseline dehydration.
Case presentation
A Caucasian 53 year-old menopausal female with fibromyalgia presented with unexplained
'burning’ pain, among others. Endocrine, nervous, and immune investigations revealed
nothing that could explain it. Her medical history included a sensitive nervous system and an
untreated lifelong low-grade dehydration. The triggering factor was traced back to a one-
month course of bio-identical progesterone that had worsened the dehydration.
The hypothalamus is involved in various ways in symptoms of fibromyalgia and stress
sensitivity, but also in the water balance regulated by the hypothalamic osmostat, so
attention turned to the hormone oxytocin. OT is seldom used in therapeutic setting, except in
obstetric care. Current research on oxytocin tends to focus on its central role in the brain,
using large doses, and on its interaction with vasopressin, affecting reproductive and social
behaviour.
A more basic role for oxytocin in the hypothalamic osmostat has become apparent through
systemic effects in this patient. A two-week intranasal treatment with low-dose OT proved
effective in resolving the burning pain, but also resulted in a general improvement, including
of hydration. This report discusses sensitivity, similarity with critical conditions, dose-related
and baffling 'inverted' effects.
The unexpected general improvement described here offers benefit for vital functions and
other ‘basic’ needs, as well as the capacity for physical self-care and compliance with a
treatment. The protocol used could be a new avenue to better match treatments to the
needs of 'sensitive' patients.
2
Introduction
Fibromyalgia is a chronic, relapsing syndrome affecting more young or middle-aged females
than males. Defined as a musculo-skeletal chronic pain syndrome (tender points, stiffness,
widespread pain, fatigue), it is notoriously difficult to diagnose and its aetiology is still
debated, often considered multi-factorial. Clinically, it is diffuse, overlapping with other
syndromes, characterised by a broad set of neurological and stress-related symptoms,
individually variable. It affects vital behaviours such as sleep, digestion, and fluid balance
(e.g. associated neurally mediated hypotension, carpal tunnel syndrome, Raynaud’s
phenomenon, etc.). It is associated with other conditions and unexplained symptoms, such as
the unbearable burning pain that is our focus here. This syndrome also affects cognition (e.g.
sensory sensitivity, concentration, memory, finding names, performing complex tasks, general
alertness), emotions (anxiety, depression), and general mood (feeling miserable, negative). It
is accompanied by functional impairment of daily living activities, to various degrees,
including social interaction, and includes an exhaustion-triggered systemic ‘shut-down’
or/and ‘brain fog’. The literature does not provide a clear prognostic image of the
syndrome’s progression, but reports gradually worsening pain, fatigue and disrupted
restorative sleep, diminishing work and physical exercise capacity, and increasing incidence
of associated degenerative diseases (rheumatoid in particular). Treatment is also multi-
faceted. Recently, fibromyalgia has been redefined as a central sensitivity syndrome (CSS)
[1], a neuro-sensory disorder.
Oxytocin was originally considered a purely female hormone (labour, lactation). The use,
from the nineteen fifties, of its chemical analogs for birth induction, in large intravenous
doses, shed light on overdose side-effects such as water intoxication. It acts peripherally
through the bloodstream on renal tissue response to increased plasma hyperosmolality, and
affects other functions. [2, 3, 4, 5] It is now known to also have a central, adaptive and stress
related role [6] as a neuro-hormone, with sexually dimorphic socio-behavioural impact [7, 8]
involving AVP (see figure 1 and additional file 1: Oxytocin).
Figure 1. Oxytocin and arginine vasopressin (AVP or ADH) differ by two amino acids.
Case presentation
This 53 year-old Caucasian menopausal female (in Australia) has displayed most of the
fibromyalgia characteristics described above for eleven years, and other progressive
conditions. She presented an unexplained ’burning pain’ in the left arm, shoulder, and neck,
resistant to her usual treatments. The pain had been recurrent for about two years, in the
sacroiliac area and spine, but more bearably, and not in the arm. The current spreading
localisation originated from a left shoulder calcific tendonopathy involving supraspinatus
(stiffness and painful restriction began in her twenties but attracted no treatment) and
involved cervical dermatomes (spondylosis consequent to a laminectomy at C6-C7 eighteen
years ago, compounded by low back pain since pregnancy and more recent thoracic kyphosis).
This pain was worse at night, increased by hypopnea, ingestion of salt or sugar or dry
processed carbohydrate foods, by physical exertion and postures restricting movement
Oxytocin Antidiuretic
hormone
3
(gardening or sitting at a computer for hours, bent). It was not improved by breathing
exercises, or nutritional and amino-acid treatments that had partially relieved other pains.
Over the past 3 years, increasing pain and the deterioration in general health were
accompanied by body fat gain, and progressive lean-mass weight loss attributed to cortisol
driven catabolism. Endocrine evaluation was consistent with various low functions, most
explained by ongoing stress and hormonal decline at menopause. No inflammatory markers
could explain the burning pain. The patient has a history of treated precancerous conditions
(and untreated multiple cherry haemangiomas from childhood, spreading). She was
investigated further but no cancerous organic damage was found in gastrointestinal track,
lungs or brain. Nerve conduction studies detected no demyelination or other neuropathy.
The acute presentation was traced back to a one-month course of bio-identical progesterone
at low-dose (2mg/day) that had induced dehydration. This effect has been described in a few
women, and deoxycorticosterone (DOC) implicated anecdotally [9]. The metabolism of
progesterone into some hormonal metabolite, probably of a type that can act as both
glucocorticoid and mineralcorticoid, suggested a relation to stress and the water metabolism.
Because this involves antidiuretic hormone (ADH, or arginine vasopressin, AVP), the oxytocin
hormone, which affects it, stood out as a possible treatment option (see discussion below).
This patient tends to display strong reactions to conventional treatments (medical drugs, and
even herbal/‘alternative’), often with counter-productive effects, so other approaches are
necessary. Small doses are usually sufficient to obtain significant results with amino-acids. A
reasonably safe approach was to choose a mild mode of peptide administration. A very low
dose would avoid the recognised side-effects (hypotension, anaphylactic-type reactions, and
water intoxication). The bio-identical OT has a different structure from that of the chemical
analog drug named Syntocinon (or Pitocin) (figure 2), and therefore, effects are bound to
display some differences. Using the bio-identical hormone promised less side-effect risk.
Figure 2. Different formulas for oxytocin and its chemical analog.
Treatment Protocol
Preparation: a commercial chemist prepared a solution of the bio-identical hormone OT at
40iu/ml dilution in an alcoholic base, in intranasal spray form.
Rate of administration: This is the dosage used for lactation, recommending several intakes
in both nostrils per day. This could be further reduced by using an ‘as-needed’ approach. The
patient was able to determine a daily dosage that was effective for the pain: 2 sprays per day
(1 nostril only each time, morning and night). This represents approximately 1.5µg/kg/day
a much smaller dose (by an order of tens to hundreds) than those habitually used in human
research and animal studies (1mg/kg/day for rodents). These are also often administered by
injection, and generally use chemical analogs.
Timing: The doses were administered primarily in response to the burning pain and to
nocturia that awoke her 2 to 4 times between 2:30 am and 4:30 am, and in early evening, to
stop facial and heel pain and open breathing passages. Once, an extra dose was added. The
prescribed maximum of 6 sprays per 24 hours was never reached. The trial treatment lasted
for 2 periods of 6 days, chosen because the research literature mentions 5 to 8 days for
repeated administration, and with a 2-day interval, to assess post-administration effects and
possible dependence.
Oxytocin:
Syntocinon:
4
Results: This treatment protocol was effective in stopping the burning pain in two weeks. It
also reduced a number of other pains and symptoms, and produced an unexpected
generalised improvement.
Discussion
The solutions mentioned to counter progesterone-induced dehydration are contradictory, and
none resolved the pain (this patient’s very low doses represent a clinical limitation). Natural
pprogesterone was discontinued, but the pain did not abate. A diarrhoea-inducing pre-
endoscopy drug treatment also triggered an acute bout of the burning. The patient reported
that pain intensity correlated with the degree of dehydration, and with other pains: in
kidneys, spleen, heel joints, bones of the face, and spine. Other symptoms of dehydration
included mild oedema (face, extremities, and abdomen), often triggered by sugar, dry
processed carbohydrates, or salt, and other symptoms such as blurred vision, difficulty
swallowing, altered urination, wildly fluctuating thirst stimulus, and bruised’ tender
sensation upon touch without visible bruising. The neural studies confirmed neural sensitivity
(a lifelong, highly strung condition without known cause, characterised by mild autonomic
dysfunction, clonic spasms, and cognitive symptoms), and reported a mild carpal tunnel
swelling.
Sensitivity and water metabolism (dehydration and swelling) were the most salient elements.
The recent redefinition of fibromyalgia offered a new perspective. As a central sensitivity
syndrome (CSS), fibromyalgia involves high sensory sensitivity and dysautonomia, low
thresholds for nociception and pain tolerance but, more relevantly here, also a sensitisation
and central deregulation of ‘the stress response system’ that can lead, in some patients, to
an auto-reinforcing neuroendocrine cascade.
A group of common characteristics suggested an avenue to explore: Effects related to pain
thresholds and sensory sensitivity (sometimes formulated in Internet documents as a ‘rheostat
turned up too high’); connection to developmental, environmental, and social variables;
sexually dimorphic responses to stress; their initiation, sensitisation, and central regulation;
the involvement of the autonomic nervous system in vigilance and arousal; the activation of
the hypothalamus-pituitary-[thyroid]-adrenal axis (HPA or HPTA axis) and of other neuro-
endocrine axes, and alterations in corticotropin-releasing hormone (CRH) neuron response
(CRH is secreted by the paraventricular nucleus of the hypothalamus) — are all elements
common to fibromyalgia and to descriptions of the actions and effects of the hormone/
neuro-hormone oxytocin (OT). The OT/ADH system in the hypothalamic osmostat is also
called ‘stress system’, and was the focus of treatment.
The detailed effects of the treatment, as observed and recorded by the patient, are
presented in tabular form, and varied with time and dose (discussed later):
-a short-term cascade effect (table 1 below)
-a cumulative effect with repeated dose (table 2 below)
-a long-term effect: stress-governed and remnant effect after 2 weeks of treatment (table 3
below).
The follow-up office visit for assessment demonstrated successful reduction of the ‘burning’.
Moreover, some other pains reduced as well (facial, heels, kidney, spleen, spine, and from
stretch stiffness). The blood pressure had risen beneficially to 95/60, a figure it had not
reached since 2002. Core temperature had risen back to 36.6°C, which other treatments
(including thyroid hormones T3/T4) had not achieved. There was a general improvement,
small but broad: in menopausal symptoms, in hydration and other vital functioning, especially
breathing and sleep, and in the capacity for physical self-care (compliance with the
nutritional schedule, getting sufficient exercise and sunshine, eating properly…), which the
patient had come to find taxing. There was no undesirable side effect to low-dose OT, even
months later. The positive effects of OT treatment lasted for about two further weeks after
the trial treatment, and then began to wane, confirming a definite role of OT in the
‘sensitive’ and declining state of this patient.
5
Her many but low-grade fluid-related symptoms are confusingly reminiscent of several
uncommon osmosis-related conditions. Striking similarities exist, for example, with diabetes
insipidus, syndrome of inappropriate antidiuretic hormone secretion (SIADH), osmotic stress
demyelination, and reset osmostat syndrome [10]. The manifestations are low-grade,
however, not connected to the high-degree critical states of medical emergency (e.g. reset
osmostat mostly occurs in critically ill patients). The first two conditions mentioned are also
contradictory or symmetric. The symptoms are located differently, in variable sets that
never fully match any recognisable disease definition. Why?
Several forms of ‘stress system’ have been invoked to explain counter-productive effects such
as systemic cellular dysfunctions, or long-term cortisol damage to the hippocampus. Since the
main three sub-systems are not directly causing this patient’s most troublesome pains, and
since symptoms in fibromyalgia may often be qualified of ‘subclinical’ (no objective findings),
could the central sensitivity of fibromyalgia implicate directly the hypothalamus and its
‘OT/ADH stress system’, in at least some particularly sensitive patients? It makes sense to
suppose that this patient’s mild dehydration and oedema might be early signs of a subclinical
osmotic strain related to initiating and stopping the stress state. The dose- and time-
dependence effects and patient observations, during this low-dose OT regimen, warrant some
comments, related to the literature and theoretical considerations. (See additional file 2:
Reflections)
Conclusion
The daily intranasal administration of oxytocin, at the unusually low dose of 1.5µg/kg/day (in
2 intakes) over 2 weeks, successfully reduced the ‘burning’ pain in this fibromyalgia patient,
but also improved unexpectedly a broader array of pains, symptoms, and vital mechanisms,
without apparent undesirable side-effects, even months later.
Maintaining these benefits for a highly sensitive patient, however, might involve a longer-
term treatment (1) with an ‘as needed’ (not necessarily daily) administration for flexibility
(OT spray is not constraining, although the aggressive alcohol content is a problem), and (2)
under conditions of limited stimulation (especially sensory and by foods).
More knowledge of oxytocin is needed in clinical family practice, about its basic physiological
effects on water metabolism, hypothalamic osmostat and vital functions, about those of low-
dose OT treatment and endogenous OT production, about osmolytes in foods/drinks and how
these affect the yet unexplained drift (‘with age’, from birth) of the baseline hydration level,
a basic but little studied need of health.
Their systemic role in inducing but also in stopping states of central, nervous or stress
sensitivity (and possibly immune reactivity), needs to be investigated with a different
framework. This could provide the physician with new means to reduce progressions and help
maintain the health of fibromyalgia and other such patients within the limitations of what a
‘sensitive’ system can manage without damage, under the normal biosocial pressures and
‘allostatic load’ of chronic environmental challenges.
References
1. Yunus MB: Fibromyalgia and overlapping disorders: the unifying concept of central sensitivity
syndromes. Semin Arthritis Rheum 2007, 36(6):339-56.
2. Gimpl G, Fahrenholz F: The Oxytocin receptor system: Structure, function, and regulation.
Physiological Reviews 2001, 81(2):629-683.
3. Carter CS: Developmental consequences of oxytocin. Physiol Behav 2003, 79(3):383-97.
4. Tyzio, R et al.: Maternal oxytocin triggers a transient inhibitory switch in GABA signaling in the
fetal brain during delivery. Science 2006, 314(5806):1788–1792.
6
5. Landgraf R, Neumann ID: Advances in vasopressin and oxytocin: from genes to behaviour to disease.
Volume 170. 1
st
edition. St. Louis: Elsevier Science; 2008.
6. Rinaman L, Sherman TG, Stricker EM: Vasopressin and Oxytocin in the Central Nervous System. In
Psychopharmacology: the Fourth Generation of Progress. 4th edition. Eds. Bloom, FE and Kupfer
DJ. Philadelphia: Lippincott Williams & Wilkins; 1995. Published online 2000, retrieved 22/05/2009
from [ http://www.acnp.org/g4/GN401000051/Default.htm ]
7. Uvnäs-Moberg K: Oxytocin linked antistress effects - the relaxation and growth response. Acta
Physiol Scand Suppl. 1997, 640:38-42. Review.
8. Uvnäs Moberg K, Francis R (translator): The Oxytocin Factor: Tapping the Hormone of Calm, Love,
and Healing. New York: Da Capo Press; 2003.
9. Lee, JR: What Your Doctor May Not Tell You About Menopause. Clayton VIC: Warner Books; 2004.
10. Lipschutz JH, Arieff AI: Reset osmostat in a healthy patient. Ann Intern Med 1994, 120:574–6.
Additional files:
Additional file 1
Title: Oxytocin in the hypothalamic osmostat stress system
File name: Added File 1 – Oxytocin (.pdf format)
Additional file 2
Title: Reflections, patient’s perspective, and theoretical considerations
File name: Added File 2 – Reflections (.pdf format)
Tables:
Table 1: Short-term cascade effects of low-dose OT treatment (patient perspective)
Table 2: Cumulative effects of low-dose OT treatment (patient perspective)
Table 3: Long-term effect of low-dose OT treatment: stress-governed and remnant effect
after 2 weeks (patient perspective)
Consent
Written informed consent was obtained from the patient for publication of this case report.
Acknowledgement
The author thanks Dr. Scott Powell of Maroochydore (Queensland, Australia), for assisting in
manuscript preparation and encouragement. No special funding supported this study.
Competing interests
The author declares that she has no competing interests.
7
Table 1: Short-term ‘cascade’ effects of low-dose OT treatment (patient perspective)
Timing from
administration
Effects noticed (on symptoms, sensations, behaviours)
Those noticed at first administration were reproduced on other days)
Within 10 seconds:
Noticed at first administration:
pain stopped in scar tissue around spinal bone
spurs at C5-C8 level
Cumulative observations over 2-week treatment:
reduced ‘sticky’ sound at the top
of the spine
Within 3 minutes:
Noticed at first administration:
reduced spinal ligaments stiffness pain in
occipital-atlas, at thoracic level, and in front of spine, and moving to other
tendons: inside rib cage and at hips-legs juncture
Cumulative observations over 2-week treatment:
kidney and spleen pain stopped;
reduced bruise-like pain; tinnitus-like whistle reduced; evening face bones
pain and heel pain stopped, also in the elbow
After 10-15
minutes:
Noticed at first administration:
mucus loosened in sphenoid sinuses;
much
reduced ‘burning pain’ in left head-to-arm connection (usually, when pain is
not ‘burning’, it is the ligaments/tendons that hurt)
Cumulative observations over 2-week treatment:
reduced stiffness and pain from
straining to stretch; mucosa moistened and mucus loosened, ‘dry’ headache
stopped.
Breathing better: less swollen breathing passages (lungs, throat; nostrils no
longer blocked or coated with dried mucus, sphenoid sinuses no longer
swollen/blocked); rib cage muscle more tonic and active, actually lifting again
(no longer expanding into belly because of weak muscles); left-right nostrils
breathing evened out (not just one open with the other one blocked, as most
of the time)
After 20-30
minutes
to day-long:
Noticed at first administration:
urge to urinate (but normal amount and clear) and mucus produced in
sphenoid sinuses and lungs (triggering one cough)
Cumulative observations aver 2-week treatment:
catabolic proteinuria pain
stopped; bowel motion(unstrained peristalsis and stool softened: counter-
constipation)
-if moving to move body fluids and activate breath: nose remains moist
-if sedentary (e.g. at computer): sphenoid sinus becomes encumbered by thick
mucus newly produced
-reduced hot flushes and relaxed agitation/tension (both are induced by sugar
and processed glucid foods, by chocolate as well as by not eating enough)
Table 2: Cumulative effects of low-dose OT treatment (patient perspective)
Timing from
administration
Effects noticed (on symptoms, sensations, behaviours)
(Those noticed at first administration were reproduced on other days)
Within 10 seconds:
repeated yawning, and stretching of body and jaw, uncontrollable;
Within 3 minutes: eyelids no longer sting (as in tired child); eyes watering: stopped dry itching;
stretch pain response reduced in spine (bending the neck forward)
Within 8-10
minutes:
spontaneous ‘yoga’ - mechanical repetitive movements of the neck bent
backwards, which loosens fibrous/calcified tendons/ligaments lower down
(located about T1-T5, inside the vertebral column); also mobilised the sacro-
illiac area mechanically. Other stretching movements mobilised and re-
‘placed’ several vertebral discs or tendons (cracking sound).
After 15-20
minutes to
day-long:
-somewhat reduced pain in ‘fighting gravity’ to lift the left arm (seat of the
burning pain), which had not been possible in over a month: easier to get
dressed, do driving manoeuvres, lift objects
-the spinal ligaments surprisingly loosened enough to stop the ‘front spring’
that had created an uncontrollable bend of the spine forward, preventing from
lying flat on the back, and causing increased automatic slouching
-reduced ‘alarm/alert’, but change in the cognitive mode to the annoying style
of chronic discursive thought that the single OT low-dose stops
-after time spent taking notes, the relaxed-active state (with lesser hypopnea)
allowed to go back to sleep
8
Table 3: Long-term effects of low-dose OT treatment:
stress-governed and remnant effect 2 weeks after treatment (patient perspective)
improved core body temperature: finally risen by half a degree, back up to 36.6°C after several
years; improved peripheral warmth distribution especially about the abdomen; less reaction to
external temperature changes
menopausal hot flushes and spinal cold disappeared
reduced problems with thirst and urination (quantity, colour, cortisol-related catabolism and
proteinuria)
improved appetite (actually feeling ‘hungry’, a sensation lost ten years ago; not forget to eat;
desire for more nourishing than ‘energy food’;
but stopped craving for sugar and other ‘energy foods’ (dry processed carbohydrates, dark
chocolate, red meat, brie cheese) – as long as stress challenges remain low
stopped clonic jerks, restless legs, and micro-muscular tension (perceptible only upon retiring at
night as a body-wide vibration)
much reduced nail biting tension(reappeared, from childhood, at menopause)
reduced dream agitation and no more waking up for burning pain
reduced hair loss & breaking, and breaking nails (not so brittle)
easier breathing, better sleep, less straining to keep up posture, easier physical self-care (going to
bed earlier, exercise, and ‘eating properly’)and treatment compliance
reduced swelling & itching (involved in the aetiology of VIN3); reduced reactions to insect bites
... Dieses Review legt nahe, dass bei Studien mit experimentell induziertem Schmerzreiz bei gesunden Probanden die Wirkung von OT weniger effektiv war im Vergleich zu Studien, welche Symptomschmerzen bei Patienten mit Migräne, Verstopfung, Fibromyalgie, Reizdarmsyndrom oder Bauchschmerzen untersuchten [2,3,9,15,23,35,40,55,57,61]. In Patientenstichproben scheint eine geringere Schmerzintensität auch mit erhöhten OT-Werten im Blut zusammenzuhängen [3,45]. ...
... Die genaue Betrachtung der Originalarbeiten deutet außerdem auf leichte Unterschiede zwischen Männern und Frauen in der Reaktion auf eine OT-Applikation hin. Männer schienen weniger von exogen zugeführtem OT zu profitieren im Vergleich zu Frauen [9,21,23,35,40,61]. ...
... Dreizehn der Studien untersuchten den Einfluss von exogen appliziertem OT und weitere 4 Studien überprüften einen möglichen Zusammenhang zwischen OT-Spiegel im Blutplasma oder in der Rückenmarksflüssigkeit und Schmerzzustand beziehungsweise Schmerzempfinden. Dabei konnte festgestellt werden, dass 8 Studien die positive Wirkweise von exogen verabreichtem OT durch Nasenspray[9,35,36,43,48,55], intrathekale Applikation[57] und durch intravenöse Injektion[40] bestätigen. Unter den 8 positiv bewerteten Studien waren 2 Fallanalysen, welche die positive Wirkung von OT bei Migräne und Fibromyalgie näher untersuchten[9,40]. ...
Article
Full-text available
HintergrundDie Wirkung des körpereigenen Hormons Oxytocin und dessen Nützlichkeit für die Schmerztherapie werden in der Forschung über die letzten Jahre vermehrt untersucht und diskutiert. Erste Studienergebnisse konnten bereits die Effekte des Hormons in Bezug auf Geburtsvorgang und Stillen hervorheben. Diverse Tierstudien konnten zudem die Wirksamkeit auf Bindungsverhalten und Schmerzempfinden belegen. Unklar ist allerdings nach wie vor, wie Oxytocin auf das menschliche Schmerzerleben wirkt. Die potenzielle therapeutische Wirksamkeit von Oxytocin könnte für die Primär- und Sekundärversorgung von Schmerzpatienten besonders bedeutsam sein, da es in diesem Bereich verstärkt zu Schmerzchronifizierung kommen kann. MethodenDie Datenbanken PubMed, Medline und PsycINFO wurden auf die Begriffe Oxytocin, „pain“, „human“, „analgesic“ durchsucht. Die Suche nach Originalarbeiten ergab insgesamt 89 Artikel, nachdem Studien zu Schmerzen bei Geburt, Stillen und Tierstudien ausgeschlossen worden waren. Es wurden nur Studien eingeschlossen, welche zwischen 1994 und 2015 durchgeführt wurden. Es konnten insgesamt 17 Studien für dieses Review verwendet werden. Davon befassten sich 13 Studien mit der Applikation von Oxytocin und 4 weitere Studien mit der Messung von Oxytocin im Plasma. SchlussfolgerungDieses Review soll einen Überblick über den aktuellen Forschungsstand von Oxytocin und dessen direkten und indirekten Zusammenhang mit dem menschlichen Schmerzerleben geben und die daraus resultierenden Konsequenzen für die multimodale Schmerztherapie hervorheben.
Article
Full-text available
The neurohypophysial peptide oxytocin (OT) and OT-like hormones facilitate reproduction in all vertebrates at several levels. The major site of OT gene expression is the magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei. In response to a variety of stimuli such as suckling, parturition, or certain kinds of stress, the processed OT peptide is released from the posterior pituitary into the systemic circulation. Such stimuli also lead to an intranuclear release of OT. Moreover, oxytocinergic neurons display widespread projections throughout the central nervous system. However, OT is also synthesized in peripheral tissues, e.g., uterus, placenta, amnion, corpus luteum, testis, and heart. The OT receptor is a typical class I G protein-coupled receptor that is primarily coupled via G(q) proteins to phospholipase C-beta. The high-affinity receptor state requires both Mg(2+) and cholesterol, which probably function as allosteric modulators. The agonist-binding region of the receptor has been characterized by mutagenesis and molecular modeling and is different from the antagonist binding site. The function and physiological regulation of the OT system is strongly steroid dependent. However, this is, unexpectedly, only partially reflected by the promoter sequences in the OT receptor gene. The classical actions of OT are stimulation of uterine smooth muscle contraction during labor and milk ejection during lactation. While the essential role of OT for the milk let-down reflex has been confirmed in OT-deficient mice, OT's role in parturition is obviously more complex. Before the onset of labor, uterine sensitivity to OT markedly increases concomitant with a strong upregulation of OT receptors in the myometrium and, to a lesser extent, in the decidua where OT stimulates the release of PGF(2 alpha). Experiments with transgenic mice suggest that OT acts as a luteotrophic hormone opposing the luteolytic action of PGF(2 alpha). Thus, to initiate labor, it might be essential to generate sufficient PGF(2 alpha) to overcome the luteotrophic action of OT in late gestation. OT also plays an important role in many other reproduction-related functions, such as control of the estrous cycle length, follicle luteinization in the ovary, and ovarian steroidogenesis. In the male, OT is a potent stimulator of spontaneous erections in rats and is involved in ejaculation. OT receptors have also been identified in other tissues, including the kidney, heart, thymus, pancreas, and adipocytes. For example, in the rat, OT is a cardiovascular hormone acting in concert with atrial natriuretic peptide to induce natriuresis and kaliuresis. The central actions of OT range from the modulation of the neuroendocrine reflexes to the establishment of complex social and bonding behaviors related to the reproduction and care of the offspring. OT exerts potent antistress effects that may facilitate pair bonds. Overall, the regulation by gonadal and adrenal steroids is one of the most remarkable features of the OT system and is, unfortunately, the least understood. One has to conclude that the physiological regulation of the OT system will remain puzzling as long as the molecular mechanisms of genomic and nongenomic actions of steroids have not been clarified.
Article
Full-text available
We report a signaling mechanism in rats between mother and fetus aimed at preparing fetal neurons for delivery. In immature neurons, γ-aminobutyric acid (GABA) is the primary excitatory neurotransmitter. We found that, shortly before delivery, there is a transient reduction in the intracellular chloride concentration and an excitatory-to-inhibitory switch of GABA actions. These events were triggered by oxytocin, an essential maternal hormone for labor. In vivo administration of an oxytocin receptor antagonist before delivery prevented the switch of GABA actions in fetal neurons and aggravated the severity of anoxic episodes. Thus, maternal oxytocin inhibits fetal neurons and increases their resistance to insults during delivery.
Stress or noxious stimuli of various kind may induce the fight-flight response. In this situation a number of physiological and behavioural adaptations leading to defense of the organism occur. At a central level increased activity in the noradrenergic locus coeruleus (LC) and an enhanced secretion of corticotrophin-releasing factor (CRF) and vasopressin produced in the paraventricular nucleus (PVN) integrate stress response. Here the existence of an opposite psycho-physiological pattern associated with relaxation and growth and which is activated by certain types of non-noxious stimuli and integrated by oxytocin is proposed. In support of this, administration of oxytocin to male and female rats gives rise to effects of antistress nature in particular after repeated administration. Thus a five day treatment period with oxytocin 1 mg/kg s.c. or 1 micro g/kg i.c.v gives rise to sedation, lowering of blood pressure, increased withdrawal latency in the tail flick test and also a decrease of corticosterone levels and a rise of certain vagally controlled hormones. Weight gain is also increased under certain conditions. These effects persist several weeks after administration of oxytocin and cannot be reversed by oxytocin antagonists when established, suggesting that secondary mechanisms have been activated. Naloxone temporarily reverses the increased withdrawal of the tail flick test suggesting that opioid mechanisms have been activated to cause this particular effect. In contrast the sedative and blood pressure lowering effect seems to be induced by an enhanced activity in central alpha 2 receptors. Oxytocin levels increase in blood and CSF after various kinds of non-noxious sensory stimulation such as touch, light pressure and warm temperature in both female and male rats. It is suggested that other types of non-noxious stimuli as well may increase oxytocin release. If so, a release of oxytocin could be responsible for not only the antistress effects occurring during lactation but also why relationships, social contact and networks may have health promoting effects in particular by preventing cardiovascular disease.
Article
This paper examines the developmental effects of the mammalian neuropeptide, oxytocin (OT). In adults, OT is the most abundant neuropeptide in the hypothalamus and serves integrative functions, coordinating behavioral and physiological processes. For example, OT has been implicated in parturition, lactation, maternal behavior and pair bond formation. In addition, OT is capable of moderating behavioral responses to various stressors as well as the reactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Neonates may be exposed to hormones of maternal origin, possibly including peptides administered to the mother in the perinatal period to hasten or delay birth and in milk; however, whether peptide hormones from the mother influence the developing infant remains to be determined. In rodents, endogenous OT is first synthesized during the early postnatal period, although its functions at this time are not well known. Experiments in neonatal prairie voles have documented the capacity of OT and OT receptor antagonists to have immediate and lifelong consequences for social behaviors, including adult pair bonding and parental behaviors, as well as the reactivity of the HPA axis; most of these effects are sexually dimorphic. Possible mechanisms for such effects, including long-lasting changes in OT and vasopressin, are summarized.
Article
To discuss fibromyalgia syndrome (FMS) and overlapping conditions, eg, irritable bowel syndrome, headaches, and chronic fatigue syndrome, within the concept of central sensitivity syndromes (CSS). A critical overview of the literature and incorporation of the author's own views. The concept of CSS seems viable. It is based on mutual associations among the CSS conditions as well as the evidence for central sensitization (CS) among several CSS members. However, such evidence is weak or not available in other members at this time, requiring further studies. The biology of CSS is based on neuroendocrine aberrations, including CS, that interact with psychosocial factors to cause a number of symptoms. CSS is an important new concept that embraces the biopsychosocial model of disease. Further critical studies are warranted to fully test this concept. However, it seems to have important significance for new directions for research and patient care involving physician and patient education. Each patient, irrespective of diagnosis, should be treated as an individual considering both the biological and psychosocial contributions to his or her symptoms and suffering.
Vasopressin and Oxytocin in the Central Nervous System In Psychopharmacology: the Fourth Generation of Progress
  • L Rinaman
  • Tg Sherman
  • Em Stricker
  • Fe
  • Dj Kupfer
  • Philadelphia
Rinaman L, Sherman TG, Stricker EM: Vasopressin and Oxytocin in the Central Nervous System. In Psychopharmacology: the Fourth Generation of Progress. 4th edition. Eds. Bloom, FE and Kupfer DJ. Philadelphia: Lippincott Williams & Wilkins; 1995. Published online 2000, retrieved 22/05/2009 from [ http://www.acnp.org/g4/GN401000051/Default.htm ]
What Your Doctor May Not Tell You About Menopause
  • Jr Lee
Lee, JR: What Your Doctor May Not Tell You About Menopause. Clayton VIC: Warner Books; 2004.