Aboubakr Elnashar

1. CNS CHANGES
IN ENDOMETRIOSIS
Prof. Aboubakr Elnashar
Benha university Hospital, Egypt
ABOUBAKR ELNASHAR

2. CONTENTS
I. DEFINITION
II. CNS CHANGES
1. Brain function
2. Brain structure
3. Decreased activity of HPA axis
4. Psychological distress
5. Autonomic nervous system changes
III. IMPLICATIONS OF CNS CHANGES
IV. LOOKING FORWARD
 CONCLUSION
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3. I. DEFINITIONS
 Nociceptive pain
Pain that arises from damage to non-neural tissue.
due to the activation of nociceptors=
sensory receptor of the peripheral nervous system
capable of transducing noxious stimuli
divided into
visceral
superficial depending on the location.
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4.  Central sensitisation
an important mechanism in endometriosis-
associated pain and CPP
Increased responsiveness of nociceptive neurons in
the CNS to their
normal or
sub-threshold afferent input:
 patient becomes more sensitive to peripheral
stimuli.
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5.  Central sensitization:
may become independent of peripheral stimuli
{via neural mechanisms similar to those underlying
the generation of memory}:
generation of pain without a peripheral noxious
input.
This may be a reason
why pain can persist despite treatment of all
identified peripheral pathology
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6. ABOUBAKR ELNASHAR

7. 1. BRAIN FUNCTION
Techniques to investigate brain function
functional MRI (fMRI)
Positron emission tomography (PET)
an indirect measurement of
metabolic activity (which increases in active
areas), as opposed to electrical activity.
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8. functional MRI (fMRI)
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9. Positron emission tomography (PET)
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10. Women with dysmenorrhea: fMRI
less peripheral input (a lower temperature)
increased activation in response to this input.
These findings suggest that:
long-lasting changes have occurred in CNS
(central sensitisation).
Women with dysmenorrhea: PET
Abnormal cerebral metabolism
[Tu et al, 2009].
Adolescence dysmenorrhoea
{CNS is very plastic in adolescence and thus changes may occur more readily}.
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11. Changes in brain function .
1. Greater resting connectivity of the anterior insula
(one of the key pain processing regions)
[As-Sanie et al, 2016].
2. Higher levels of excitatory neurotransmitters in
the anterior insula
suggesting a mechanism by which hyperalgesia may develop
in these women.
these central changes are not due to endometriosis
itself, but rather the pain that arises from it.
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12. 2. BRAIN STRUCTURE
 Alterations in the volume of specific brain
regions
[May, 2011].
 Increase in volume
{an increase in activity}
 Decrease in volume
cell death
irreversible.
once brain cells have died they are not replaced.
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13. Changes:
1. Decreased grey matter volume in brain regions
involved in pain perception.
(Sanie et al , 2012].
presence of pain, not endometriosis per se that is
related to these structural changes.
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14. 2. Increased volume of the peri aqueductal grey
(PAG)
(Coxon et al, 2018)
positively correlated with the pressure threshold required to
induce pain.
PAG:
region of descending pain inhibitory system
an endogenous mechanism of analgesia
this finding may explain
why some women with endometriosis don’t
experience pain.
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15. 3. HPA AXIS dysfunction
HPA axis is suppressed.
Acute stress:
activation of the HPA axis and a rise in cortisol
levels
however, over time this response will be
attenuated; colloquially known as burn out.
Reduced levels of serum cortisol in women with
dysmenorrhoea compared to healthy pain-free
controls
[Vincent et al, 2011].
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16. 4. PAIN PSYCHOLOGY
 can alter the pain experience by biological mechanisms, in both
healthy individuals and those with chronic pain
[Brown et al, 2014].
interactions between mood and pain experience are of relevance
in the context of endometriosis.
Depressed mood, anxiety, expectation of and attention
to pain:
higher ratings of pain intensity.
[Tracey, 2010}
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17. Depression:
chronic pain
different pain processing pathways .
prefrontal cortex is an important player in the
relationship between depression and pain severity
[Schweinhardt et al, 2008].
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18. Anticipation and expectation of pain
associated with endometriosis
Dysmenorrhoea
Dyspareunia
dyschezia
differ from other chronic pain conditions where the pain
is either less predictable or more constant in nature and
severity
(Coxon et al, 2018)
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19. 5. AUTONOMIC NERVOUS SYSTEM
of relevance due to its central effects
Parasympathetic nervous system is
antinociceptive
Sympathetic nervous system
pronociceptive.
(Coxon et al, 2018)
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20. Autonomic nervous system is important in pain
perception
[Aziz et al91].
two clusters
 that differed in both baseline measures and their
response to painful stimuli.
 stable across time.
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21. The morphology of the brain varies with autonomic
nervous system function
In chronic pelvic pain
significantly higher incidences of autonomic
symptoms
(Janicki et al, 2013)
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22. ABOUBAKR ELNASHAR

23. III. IMPLICATIONS OF CNS CHANGES
CNS
may amplify or
even generate pain in association with a peripheral
pathology such as endometriosis.
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24. Endometriosis is associated with a variety of other
comorbidities including
 autoimmune and
 endocrine disorders
 these relationships may in part be explained by
altered function of the HPA axis
autonomic nervous system
(Sinaii et al, 2002)
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25. CNS changes associated with endometriosis
may be responsible for other features commonly
described in the endometriosis.
it is well known that endometriosis is comorbid with other
chronic pain conditions
Whilst, this may be due to genetic or environmental
factors that increase the risk of both conditions
(Lee et al, 2017)
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26. CNS changes associated with endometriosis
 occur secondary to repeated episodes of pain
±predispose to other chronic pain conditions.
dysfunction in descending pain modulation or HPA axis
activity could both lead to acute or chronic pain from what
might previously have been an innocuous insult.
(Coxon et al, 2018)
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27. CNS changes associated with endometriosis
Can explain
1. why therapies directed at the periphery fail to
(sufficiently) relieve pain, and pain becomes
increasingly difficult to treat.
2. disparity between the extent of disease
observed at laparoscopy and the pain
experienced
3. persistence of pain despite adequate surgical
treatment.
(Coxon et al, 2018)
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28. Endometriosis-associated pain
can be both generated and modulated at a number
of different sites throughout the body.
is a chronic pain condition rather than purely a
peripheral pathology:
explain many of the symptoms and comorbidities
that have long been described by patients but dismissed by
clinicians as unrelated.
(Coxon et al, 2018)
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29. IV. LOOKING FORWARD
Future treatments
both targeting the
peripheral environment and
central pain mechanisms
for endometriosis-associated pain
neuropathic adjuncts e.g.
Amitriptyline
Gabapentin
duloxetine
psychological
behavioural therapies.
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30. Multi-disciplinary team clinics
Pain psychologist
Gynaecologist
Pelvic pain physiotherapist
already exist in a handful of centres
deliver
traditional”hormonal
surgical therapies
chronic pain management
clinical success
high levels of patient satisfaction
[Chen et al, 2015]
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31. Personalised medicine
move beyond looking for a “one size fits all”
treatment
aim to identify and then treat an individuals specific
combination of pain generating, maintaining and
modulating factors.
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32. CONCLUSIONS
Central changes in endometriosis-associated pain
1. Brain function: changes in the activity and
connectivity of different brain areas
2. Brain structure: altered brain area volumes
3. Decreased activity of HPA axis
4. Psychological distress
5. Autonomic nervous system changes
 Assessing pain itself rather than the presence of
endometriosis has led to significant advances.
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33. Endometriosis-associated pain
should be assessed depending on its characteristics,
not simply the intensity of the pain
multidisciplinary therapeutic strategies are
recommended
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34. ABOUBAKR ELNASHAR
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