Fibromyalgia 2010.ppt
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FIBROMYALGIA
Oleh : dr Sugianto SpS, Mkes, PhD
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hat is Fi!ro"#algia $FMS%&
A 'lini'al syndrome 'hara'teri(ed !#)idespread "us'ular pain$usuall#'hroni'%,
fatigueand
"us'le tenderness $tender points%
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hat is FMS& $'ont*%
Additional s#"pto"s are 'o""on andin'lude:
poor sleepal"ost al)a#s heada'hes irrita!le !o)el s#ndro"e 'ogniti+e and "e"or# pro!le"s nu"!ness and tingling in ngers and
toes
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hat is FMS& $'ont*%
- irrita!le !ladder
- te"poro"andi!ular .oint $/M0% disorder
- restless leg s#ndro"e
- dr# e#es and dr# "outh- "orning sti1ness
- an2iet# and depression
Symptoms including pain may wax andwane over time
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/he disease s#"pto"s e2a'er!ate instress, 3ear, 'old, hu"idit# and 3atigue*
It should !e e"phasi(ed that!ro"#algia 'an also !e indu'ed !#e"otional stress, surger#, trau"a orh#poth#roidis"*
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hat 'auses FMS&
4ause is unknown A!nor"all# high le+els o3 Su!stan'e P in
spinal 5uid in so"e patients Su!stan'e P i"portant in trans"ission
and a"pli'ation o3 pain signals to and3ro" !rain
67olu"e 'ontrol8 is turned up too high in
!rain9s pain 'enters
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hat 'auses FMS& $'ont%
Fa"ilial tenden'# to de+elop FMSsuggests genetic role
4an !e triggered !# ph#si'al, e"otionalor en+iron"ental stressors su'h as 'ara''idents, repetiti+e in.uries and 'ertaindiseases
Patients )ith Rheu"atoid arthritis andSL $Lupus% are "ore likel# to de+elopFMS
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hat 'auses FMS& $'ont*%
Other 'onditions su'h as L#"e diseaseand o!stru'ti+e sleep apnea $OSA% ha+e!een asso'iated )ith FMS
Sleep depri+ation )ith disruption o3delta-)a+e sleep $non-RM stage I7% isasso'iated )ith da#-ti"e 3atigue and
!ro"#algia s#ndro"e
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ho gets FMS&
A1e'ts as "an# as ; in
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S#"pto"s in Fi!ro"#algiaS#"pto"s in Fi!ro"#algia
S#ndro"eS#ndro"eSYMPTOMS MEAN
!"
Musculoskeletal
Pain at "ultiple sites ;==
Sti1ness >?
6@urt all o+er8 ?
S)ollen 3eeling in tissues
Morning 3atigue >= #ears )here it'an e2'eed > o3 the general population in)o"en*
* Fi!ro"#algia signi'antl# i"pairs 3un'tion,
in'reases )ork a!senteeis" and generalhealth'are use and results in a pro3ounddeterioration o3 the ualit# o3 li3e o3 patients$@o1"an and Dukes, == hite et al*, ==%*
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A4Q/ AHD 4@ROHI4 PAIH
* A'ute pain is sel3-li"iting and ser+es toprote't !iologi'al 3un'tion !# )arning o3tissue da"age* It is rarel# asso'iated
)ith ps#'hologi'al s#"pto"s other than"ild an2iet#*
* 4hroni' pain ser+es no prote'ti+e!iologi'al 3un'tion and instead it is adisease pro'ess itsel3* 4hroni' pain is not
sel3-li"iting and 'an persist 3or #ears*
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Chronic Pain Defined by
Mechanisms
Peripheral$no'i'epti+e% Pri"aril# due to
in5a""ation or da"age inperipher#
HSAID, opioid responsi+e
Beha+ioral 3a'tors "inor
2a"ples
OA A'ute pain "odels
$e*g* third "olar, post-surger#%
RA
4an'er pain
4entral $non-no'i'epti+e% Pri"aril# due to a 'entral
distur!an'e in pain
pro'essing /ri'#'li' responsi+e Behavioral factors more
prominent 2a"ples
Fi!ro"#algia Irrita!le !o)el
s#ndro"e /ension and "igraine
heada'he Interstitial '#stitis E
+ul+od#nia, non-'ardia''hest pain E et'*
Mi2ed
Heuropathi'
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O+erlap !et)een Fi!ro"#algiaand Other 6S#ste"i'8
S#ndro"es:4hroni' Multi-s#"pto" IllnessesFIBROMYALGIA
- o3 populationdened !# )idespread
pain and tenderness
JPOSQRSYHDROMSe*g*Gul3 ar Illnesses, sili'one
!reast i"plants, si'k !uildings#ndro"e
4@ROHI4 FA/IGQSYHDROM; o3population 3atigue anE 6"inor 'riteria8
SOMA/OFORMDISORDRS o3population "ultipleune2plaineds#"pto"s - noorgani' ndings
MQL/IPL 4@MI4ALSHSI/I7I/Y- s#"pto"s in"ultiple organ s#ste"s inresponse to "ultiple
su!stan'es
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PAIH PA/@AYS AHD MODQLA/ORS OFPAIH PR4P/IOH
Peripheral a1erent neurons 'ondu'tno'i'epti+e input 3ro" the peripher# tothe dorsal horn o3 the spinal 'ord and
through +arious nu'lei to higher !rain'entres su'h as the 'orte2, thala"us andh#pothala"us, )hi'h pla# a role in painper'eption*
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/he periauedu'tal gra# $PAG% pro'esses !othas'ending and des'ending pain signals, 3ro"and to the dorsal horn, and represents a link!et)een higher 'ere!ral stru'tures and thespinal 'ord*
Des'ending e2'itator# 'onne'tions 3ro" thePAG go to the rostral +entro"edial "edulla$R7M% and dorsolateral pontine stru'ture$DLP%, )hi'h, in turn, send inhi!itor#pro.e'tions to the spinal 'ord thus "odulatingantino'i'epti+e e1e'ts*
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In the dorsal horn, e2'itation o3peripheral a1erent neurons 'auses therelease o3 the e2'itator# trans"itter,
gluta"ate, )hi'h a'ts at posts#napti'HMDA $H "eth#l-D-aspartate% and AMPA$a-a"ino--h#dro2#-
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/hese signals are "odulated !# neurokinins,su'h as su!stan'e P and neurokinins A and B)hi'h are 'oreleased 3ro" pri"ar# a1erentner+e ter"inals )ith gluta"ate and a't at
posts#napti' H;, H and H re'eptors* 7asoa'ti+e intestinal peptide $7IP%, 'al'itonin
gene-related peptide $4GRP%, andso"atostatin are also released 3ro"
peripheral a1erent neurons to a't at theirrespe'ti+e posts#napti' re'eptors lo'alisedon the dorsal horn pro.e'tion neurons
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the no'turnal 3all in saturation, )hi'h"ight also underlie other diseases#"pto"s, also suggests that "us'le
h#po2ia 'ontri!utes to the pain etiolog#* Serotonin de'ien'# and in'reased P
su!stan'e le+els in the 'ere!rospinal5uid pla# an i"portant role in thepathogenesis o3 the disease*
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Pain is su!.e'ti+e the onl# "easure o3 painis a patients report*
Opti"al treat"ent o3 pain reuires
addressing the ph#si'al, ps#'hologi'al,so'ial, and spiritualEe2istential di"ensionso3 the person e2perien'ing the pain*
Phar"a'ologi' treat"ent o3 pain reuiresan understanding o3 the underl#ingpathoph#siolog# o3 the pain $ie, )hetherpain is no'i'epti+e, neuropathi', or "i2ed%*
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Neuropat)ic pain
Heuropathi' pain, 'aused !# +arious'entral and peripheral ner+e disorders, isespe'iall# pro!le"ati' !e'ause o3 its
se+erit#, 'hroni'it# and resistan'e tosi"ple analgesi's*
/he 'ondition a1e'ts K o3 thepopulation
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A'ute +s 4hroni' Pain
Characteristic Acute Pain Chronic Pain
Cause +enerally !nown ften un!nown
-uration of pain .hort,well/characteri0ed
$ersists after healing,
3 months
1reatment
approach
Resolution of
underlying cause,usually self/limited
2nderlying cause and pain
disorder outcome is oftenpain control, not cure
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Do"ains o3 4hroni' Pain
Social *onse+uences
MaritalE3a"il#relations
Inti"a'#Ese2ual a'ti+it#
So'ial isolation
Socioeconomic
*onse+uences
@ealth'are 'osts
Disa!ilit#
Lost )orkda#s
Quality of Life$hysical functioningAbility to perform
activities of daily living4or!
Recreation
Psychological Morbidity-epressionAniety, anger.leep disturbances5oss of self/esteem
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Mixed
TypeCaused by a
combination of both
primary in6ury and
secondary effects
Ho'i'epti+e +s Heuropathi'Pain
Nociceptie
PainCaused by activity in
neural pathways in
response to potentially
tissue/damaging stimuli
Neuropathic
Pain7nitiated or caused by
primary lesion or
dysfunction in the
nervous system
Postoperatie
pain
Mechanical
lo! bac" pain
#ic"le cell
crisis
Arthritis
Postherpetic
neuralgia
Neuropathic
lo! bac" pain
C$P#%
#ports&exercise
in'uries
8Comple regional pain syndrome
Central post(
stro"e pain
Trigeminal
neuralgia
Distal
polyneuropathy
)eg* diabetic* +,-.
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Possi!le Des'riptionso3 Heuropathi' Pain
Sensations nu"!ness tingling !urning parestheti' paro2#s"al lan'inating ele'tri'like
ra) skin shooting deep, dull, !onelike a'he
Signs,Symptoms allod#nia: pain 3ro" a
sti"ulus that does notnor"all# e+oke pain
ther"al "e'hani'al
h#peralgesia: e2aggeratedresponse to a nor"all#pain3ul sti"ulus
Ph i l 3 P i P ti
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Ph#siolog# o3 Pain Per'eption
/ransdu'tion /rans"ission Modulation Per'eption Interpretation Beha+ior
,n'ury
DescendingPath!ay
PeripheralNere
Dorsal$oot/anglion
C(0iber
A(beta 0iber
A(delta 0iber
AscendingPath!ays
Dorsal+orn
1rain
#pinal Cord
Adapted with permission from 4eb9- .cientific American9edicine(23
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Heuropathi' pain, 'aused !# a lesion o3the ner+ous s#ste", is espe'iall#pro!le"ati' !e'ause $a% it is o3ten
e2perien'ed in parts o3 the !od# thatother)ise appear nor"al, $!% it isgenerall# 'hroni', se+ere and resistantto o+er-the-'ounter analgesi's, and $'% it
is 3urther aggra+ated !# allod#nia$tou'h-e+oked pain%*
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It "a# result 3ro" +arious 'auses thata1e't the !rain, spinal 'ord andperipheral ner+es, in'luding 'er+i'al or
lu"!ar radi'ulopath#, dia!eti'neuropath#, 'an'er-related neuropathi'pain, postherpeti' neuralgia, @I7-relatedneuropath#, spinal 'ord in.ur#, trige"inal
neuralgia and 'o"ple2 regional pains#ndro"e t#pe II, a"ong others*
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*linical presentation
/he !lo'kade o3 ner+e 'ondu'tion in neuropathi''onditions 'auses ner+e d#s3un'tion, )hi'h 'anresult in nu"!ness, )eakness and loss o3 deeptendon re5e2es in the a1e'ted ner+e area*
Heuropathi' 'onditions also 'ause a!errants#"pto"s o3 spontaneous and sti"ulus-e+okedpain* Spontaneous pain $'ontinuous orinter"ittent% is 'o""onl# des'ri!ed as !urning,
shooting or sho'k-like* Sti"uluse+oked painin'ludes allod#nia $pain e+oked !# a nonpain3ultou'h% and h#peralgesia $in'reased pain e+oked!# a pain3ul sti"ulus%*
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9an with postherpetic neuralgia in the left fifth and sith
thoracic dermatomes( Red lines delineate area of sensory loss,and blac! dashed lines delineate area of allodynia "touchevo!ed
pain#( ;tension of allodynia above and below the originally
affected dermatomes is a feature of central sensiti0ation
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Pat)op)ysiology
Regeneration a3ter ner+e in.ur# results inthe 3or"ation o3 neuro"as and sproutingo3 ne) ner+e pro.e'tions a"ong
unin.ured neigh!ouring neurons* 4ollateral sprouting then leads to altered
sensor# properties that "a# !e reali(edas e2panded re'epti+e elds*
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@ighlights the 'lini'al andpathoph#siologi' 3eatures o3 'o""onneuropathi' pain s#ndro"es that are
'aused !# ner+e in.ur# or d#s3un'tion* no)ledge o3 the 'ellular and "ole'ular
"e'hanis"s o3 neuropathi' pain hasad+an'ed )ith the de+elop"ent o3+arious e2peri"ental "odels o3 ner+e
in.ur#
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Perip)eral mec)anisms
Regeneration a3ter ner+e in.ur# results inthe 3or"ation o3 neuro"as and sproutingo3 ne) ner+e pro.e'tions a"ong
unin.ured neigh!ouring neurons* 4ollateral sprouting then leads to altered
sensor# properties that "a# !e reali(edas e2panded re'epti+e elds
i ) l ) i
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Perip)eral mec)anisms%" Qn'ontrolled neuronal ring a3ter
e2peri"ental ner+e in.ur# is largel# attri!utedto in'reased e2pression o3 sodiu" 'hannels*
/his "e'hanis" is supported !# se+eral lineso3 e+iden'e, in'luding !lo'kade o3 neuropathi'pain )ith sodiu"-'hannelK!lo'king lo'alanestheti's*
De"#elination o3 diseased ner+es "a# !eanother 'ause o3 in'reased neuronale2'ita!ilit#*
i ) l ) i
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Perip)eral mec)anisms-" 'al'iu" 'hannels is also in'reased
3ollo)ing ner+e in.ur#* 4al'iu" entr#through +oltage-gated 'al'iu" 'hannels is
ne'essar# 3or the release o3 su!stan'e Pas )ell as gluta"ate 3ro" in.uredperipheral ner+es*
ithin the dorsal root ganglion, in'reased
e2pression o3 the T--delta su!unit o3+oltage-gated 'al'iu" 'hannels 'orrelates)ith onset and duration o3 allod#nia*
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*entral mec)anisms
Sustained pain3ul sti"uli result in spinalsensiti(ation, )hi'h is dened asheightened sensiti+it# o3 spinal neurons,
redu'ed a'ti+ation thresholds andenhan'ed responsi+eness to s#napti'inputs $i*e*, "ore likel# to trans"it pain tothe !rain%*
4entral sensiti(ation is largel# "ediated!# the H-"eth#l-Daspartate $HMDA%re'eptor*
S ) i ll
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Sympat)eticallymaintained pain/he i"portan'e o3 the s#"patheti' ner+ous
s#ste" in neuropathi' pain has !eende"onstrated !# analgesia 3ollo)ings#"pathe'to"# in ani"als and hu"ans, and
!# pain e2a'er!ation through a'ti+ation o3 thes#"patheti' ner+ous s#ste"*
S#"patheti'all# "aintained pain "a# !ee2plained !# sprouting o3 s#"patheti' neuronsinto dorsal root ganglia o3 in.ured sensor#neurons and postin.ur# sprouting o3s#"patheti' !res into the der"is*
P i f l 'i . ti
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Painful 'ia.eticNeuropat)y Mechanisms of Pain
/he 'urrent understanding o3 general "e'hanis"s o3neuropathi' pain "a# pro+ide insights into thea!nor"alities leading to pain in dia!eti' neuropath#*
Da"age to peripheral ner+es results in h#pere2'ita!ilit#in pri"ar# a1erent no'i'eptors $peripheral sensiti(ation%
that leads to h#pere2'ita!ilit# in 'entral neurons $'entralsensiti(ation% and generation o3 spontaneous i"pulses)ithin the a2on as )ell as the dorsal root ganglion o3these peripheral ner+es
P i f l 'i . ti
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Painful 'ia.eticNeuropat)y Mechanisms of Pain
@#pere2'ita!ilit# o3 the peripheral ner+es results in'entral h#pere2'ita!ilit#, and persistent ner+e
sti"ulation a'ti+ates H-"eth#ld Kaspartate $HMDA%re'eptors lo'ated posts#napti'all# in the dorsal horn,)ith su!seuent gluta"ate release Gluta"ate is ane2'itator# neurotrans"itter that 'auses neuronal"e"!rane depolari(ation, allo)ing sti"uli to produ'e
"u'h larger posts#napti' potentials than usualUapro'ess kno)n as s#napti' potentiation* Long-ter"s#napti' potentiation has !een sho)n in +arious painstates
Pathoph#siolog# o3 'o""on
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Pathoph#siolog# o3 'o""onneuropathi' pain s#ndro"es
@#pergl#'e"ia,h#perlipide"ia,h#poinsuline"ia, gro)th 3a'tor de'ien'#o2idati+e stress and autoi""unit#
progressi+e de"#elination and a2onalloss sensor# loss, paresthesia,d#sesthesias, pain and allod#nia
Type 4
D,A15T5#
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D,A15T5#
+yperglycemia+ypoinsulinemia
Polyol
path!ay
A/5
production
6xidatie
stress
Neurotrophin
deficiency
Mitochondria
l
dysfunction
ATP 7
,mpairment in Decreased Decreased
calcium axonal protein
homeostasis transport synthesis
Distal axonal
degenerationPathological changes
in nere* microessel* and ganglia
7 7
5T,6L6/,CAL PAT+8A9# ,N D,A15T,C N5:$6PAT+9 )Phernyhough 3;;<
Sensor distri!ution o3
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Sensor# distri!ution o3Dia!eti' Peripheral Heuropath#
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SMMS IHS/IH MOHOFILAMH/ /S/
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A1N6$MAL,T,5# 60 ,#6LAT5D 0,15$# ,N L5N/T+(D5P5ND5NT D,A15T,C PNP
)#aid 3;;=.A> Normal 1> #egmental demyelination associated !ith distal axonal degeneration
C> $emyelination !ith replacement of the original internode !ith 3 shorter internodes ?
axonal regeneration by sprouting of proximal axonal stump
D> $emyelination of axonal sprouts of the fiber
@
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Su""ar#
4hroni' neuropathi' pain is a disease, not as#"pto"
6Rational8 pol#phar"a'# is o3ten ne'essar# 'o"!ining peripheral and 'entral ner+ous s#ste"
agents enhan'es pain relie3
/reat"ent goals in'lude: !alan'ing eC'a'#, sa3et#, and tolera!ilit#
redu'ing !aseline pain and pain e2a'er!ations
i"pro+ing 3un'tion and VOL
He) agents and ne) uses 3or e2isting agentso1er additional treat"ent options
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/HSIOH-/YP @ADA4@
Pain is usuall# "ild to "oderate inintensit# , !ut in'reases )ith an in'reasein heada'he 3reuen'# *
pisodi' tension-t#pe heada'he $//@%is al"ost e2'lusi+el# !ilateral $W=%and is usuall# des'ri!ed as 6!andlike8and a1e'ts, in order o3 3reuen'#, the
o''ipital, parietal, te"poral, or 3rontalareas
Diagnosti' 4riteria: pisodi' /ension /#pe
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Diagnosti' 4riteria: pisodi' /ension-/#pe@eada'hea
Freuent //@
A* At least ;= episodes o''urring X; !ut ;< dE"o 3or at least "o $X; and ;= dE#r% and 3ullling 'riteria BUD
B* @eada'he lasting 3ro" = "in to > d
4* @eada'he has at least t)o o3 the 3ollo)ing 'hara'teristi's:
a*Bilateral lo'ation
!*PressingEtightening $nonpulsating% ualit#
'*Mild or "oderate intensit#
d*Hot aggra+ated !# routine ph#si'al a'ti+it# su'h as )alking or
'li"!ing stairs
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Pain is usuall# !ilateral $o''uring on !oththe le3t and right side o3 the head% andhas a pressing or tightening 3eeling )ith
a pain intensit# 3ro" "ild to "oderate*/he pain does not in'rease )ith ph#si'al
a'ti+it# and no nausea is asso'iated )iththis t#pe o3 heada'he* It is not
un'o""on 3or a su1erer to !e o+erl#sensiti+e to light or sound*
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RFRH4
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RFRH4
alla'e, Daniel 0* 4lau), Daniel 0* ==