chronic pelvic pain en dome trios is
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CHRONIC PELVIC PAIN--
ENDOMETRIOSIS
Chronic pelvic pain is acommon
symptom,common to anumber ofdifferent conditions/disorders/disease
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CHRONIC PELVIC PAIN--ENDOMETRIOSIS
Chronic pelvic pain is acommonsymptom,common to anumber of differentconditions/disorders/disease
SO : DO WE FOCUS ON THE PAIN or THEENDOMETRIOSIS?how can we frame the
question? How are mechanisms of chronic pelvic pain
influenced by endometriosis?
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PAIN MECHANISMS?
TRADITIONAL
Pain Pathway
Pain enters
here..
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PAIN MECHANISMS?
TRADITIONAL
Pain PathwayPain enters
here..
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Chronic Pain
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FROM : Straffon P,berkley ki.Chronic pelvic pain and endometriosis; tranlational evidence of the
relationship and implications. Human reprod update 2011 :17:327.346.
SIGNS?
LESIONS Rat model of
endometriosis
Women with
endometriosis
Refs rat Refs human
Etiology of
lesions
Surgically
induced
Endogenous origin Vemn&wil
son 1965
G/udice and
Kao 2004
bullun 2009Location of
lesions
Restricted to
abdomen
Varied, bur
predominately pelvis
Vermon &
wilson
1965
G/udice and
Kao 2004
Stegmann et al
2000
Appearance
composition
Cystic ; full
uterine horn
(endometrium,
myometrium
and stroma)
Varied appearance
(mainly
endometrium and
stroma)
Vermon &
wilson
1965
Fauconner and
chapron 2005
Stegmann et al
2009
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FROM : Straffon P,berkley ki.Chronic pelvic pain and endometriosis; tranlational evidence of the relationship and implications. Human
reprod update 2011 :17:327.346.
SYMPTOMS Rat model women Refs rat Refs human
dysmenorrhea Rats not menstruate YES Fauconnier & Chapron
05
Dyspareunia/vaginal
hyperalgesia
YES YES Cason et al 03 Anaf et al 02
Ovarian cyclicity of
dyspareunia
Correlates with estradiol
& uter.cts
UNKNOWN Cason et al 03 wray &
noble 08
Refered muscle
hyperalgesia
YES YES Nagabukuro & berkley
07
Jarrell 04
Location of reffered
muscle pain
abdomen Pelvis/ abdomen Nagabukuro & berkley
07
Jarrell 04
Ovarian cyclicity of
reffered hyperalgesia
Yrs : correlates with
estriol & uter.cts
UNKNOWN Nagabukuro & berkley
07
Wray & Noble 08
Uroogical symptoms Bladder hyperreflexia freq / urgcy Morrison et al 08 Heitkemper & jarrett 05
; Vercelini et al 09
Pain w/kidney stones & more cyclic Giamberanano et al 02 Giamberanano et al 01
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BUT : ARE THE ECTOPIC GROWTHS
INVOLVED
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BUT : ARE THE ECTOPIC GROWTHS
INVOLVED
IN WOMEN Removing lesions can alleviate pain long term in 25%
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ENDO, but not shamEndo, produces
vaginal hyperalgesia
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Surgical removal of the cysts
eliminates the hyperalgesia
McAlister SL et al, pain 2009 147 255 64
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HOW MIGHT THE CYSTS / GROWTH BE
ASSOCIATED WITH THESE EFFECTS
1. The growths must be vascularized to survive
2. Blod vessels are innerated by sensry and
sympathetic nerve fibers3. Do these nerves accompany blood vessels as
they vascularize the growths?
4. In other words , do the nerve fibers sprout toinnervate the growths?
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INNERVATION?
Anaf V, Simon P,el Nakadi I, Fayt I, Simonart T,Peny MO and Noel JC (2000) relationshipbetween endometriotic foci and nerves inrectovaginal endometriotic nodules. Hum reprod15 : 1744-1750
Anaf V, Simon P,el Nakadi I, Fayt I, Simonart T,Peny MO and Noel JC (2002) Hyperalgesia, nerveinfiltration and nerve growth factor expression in
deep adenomyotic nodules, peritoneal andovarian endometriosis. Hum reprod 17.1895-1900
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INNERVATION?
INNERVATION
OF LESIONS
Rat model of
endo metriosis
Women with
endometriosis
Refs rat Refs human
Sensory YES YES Berkley et al 04 Berkley et al 05
tokushige et al
06
Sympathetic YES YES Berkley et al 04 Berkley et al 05
Tokushige at al
06
Hormonal
influences
Correlates with
estradiol,Dyspareunia,&
uterine
contract
Innervation
byprogestogens
or combined
oral
contraceptives
Wray & Noble
08: Zhang et al08
Tokushige at al
06
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How are mechanisms of chronic pain
influenced by endometriosis
Fibers that sprout from existing nerves into lesions
FROM : Dmitrieva N,Nagabukuro H,Reseuhr D,Zhang GH,Mc Allister SM, McGinty KA,
Berkley KJ. Endocannabinoid involvment in endometriosis pain 2010 ; 161 : 703-10
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How are mcehanisms of chronic pain
influenced by endometriosis
FROM : Dmitrieva N,Nagabukuro H,Reseuhr D,Zhang GH,Mc Allister SM, McGinty KA,
Berkley KJ. Endocannabinoid involvment in endometriosis pain 2010 ; 161 : 703-10
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FROM : Dmitrieva N,Nagabukuro H,Reseuhr D,Zhang GH,Mc Allister SM, McGinty KA,
Berkley KJ. Endocannabinoid involvment in endometriosis pain 2010 ; 161 : 703-10
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Clearly multiple intercting factors can contribute
to chronic pain in the context of endometriosis
Peripheral nerve sprouting(sensory/symphatetic)sensitization
Central sensitization (initiation &maintenance)
-----------------------------
Hormonal status
Local inflammation
Peritoneal fluid components
Gene expression
Stress
Eutropic uterus
1 A.As-Sanie.R Harris G, Neshewat,AKairys,D Williams,D Clauw, TSchmidt Wicke
Altered regional brain morphology inwomen with endometriosis andchronic pain
2. X Mao Y Zheng,Q MA S-W guo
Oxytocin receptor expression and itsrelationship with uterine contraction
3.N Santanam, c kocher C Cook B DawleyPain sensitive micro RNAs in womenwith endo metriosis
4.M.L barcena de arellanoJ.arnold,Vercelino,V Chiantera,Aschneider,S Mechsner Evidence of
neutrophic events due toperitonealendometriotic lesions
5.J.Arnold M.I barcena de Arellano C Ruster,S Mechsner Imbalance of symphateticand sensory innervation in peritonealendometriotic lesions
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Peripheral nerve
sprouting
(sensory/symphatetic)
sensitization
Central sensitization(initiation &
maintenance)
-----------------------------
Hormonal status
Local inflammation
Peritoneal fluidcomponents
Gene expression
Stress
Eutropic uterus
1 A.As-Sanie.R Harris G, Neshewat,A Kairys,D
Williams,D Clauw, T Schmidt Wicke
Altered regional brain morphology in women
with endometriosis and chronic pain
2. X Mao Y Zheng,Q MA S-W guo
Oxytocin receptor expression and its
relationship with uterine contraction
3.N Santanam, c kocher C Cook B Dawley Pain
sensitive micro RNAs in women with endo
metriosis
4.M.L barcena de arellano J.arnold,Vercelino,V
Chiantera,A schneider,S Mechsner
Evidence of neutrophic events duetoperitoneal endometriotic lesions
5.J.Arnold M.I barcena de Arellano C Ruster, S
Mechsner Imbalance of symphatetic and
sensory innervation in peritoneal
endometriotic lesions
Clearly multiple intercting factors can contribute to
chronic pain in the context of endometriosis
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Nociceptive pain :
Pain Perception
(Trauma,inflammation,etc)Pain
Stimulus
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Spesifik aims
To use VBM to determinne if women with CPP,
with and witahout endometriosis, display
changes brain morpholgy,especially in regions
knw to be involved in pain processing, in
cmparison to age matched healthy controls
To examine if cuch changes are prsent an all
women with endometriosis or just those withchronic pain symptoms.
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Participants
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