PATHOPHYSIOLOGY OF PAIN

Prof. J. Hanek, MD, PhD

Technical co-operative: L.urinov, Ing. M. Vrabec

 Alteration in en or! f"n#tion $! f"n#tion of the %eneral or &e#ial en e ' D! f"n#tion of the %eneral en e #hroni# &ain, a(nor)al te)&erat"re re%"lation, ta#tile $! f"n#tion

Definition of &ain
' Pain i a #o)&le* "n&lea ant &heno)enon #o)&o e$ of en or! e*&erien#e that in#l"$e ti)e, &a#e, inten it!, e)otion, #o%nition, an$ )oti+ation ' Pain i an "n&lea ant or e)otional e*&erien#e ori%inatin% in real or &otential $a)a%e$ ti "e ' Pain i an "n&lea ant &heno)enon that i "ni,"el! e*&erien#e$ (! ea#h in$i+i$"al; it cannot be adequately de ined, identi ied, or !ea"ured by an ob"erver

The e*&erien#e of &ain

Three ! te) intera#t " "all! to &ro$"#e &ain.. en or! / $i #ri)inati+e 0. )oti+ational / affe#ti+e 1. #o%niti+e / e+al"ati+e
.. Sen or! / $i #ri)inati+e ! te) &ro#e e infor)ation a(o"t the tren%th, inten it!, ,"alit! an$ te)&oral an$ &atial a &e#t of &ain 0. Moti+ational / affe#ti+e ! te) $eter)ine the in$i+i$"al2 a&&roa#h/a+oi$an#e (eha+io"r 1. 3o%niti+e / e+al"ati+e ! te) o+erlie the in$i+i$"al learne$ (eha+io"r #on#ernin% the e*&erien#e of &ain. It )a! (lo#k, )o$"late, or enhan#e the &er#e&tion of &ain

Pain #ate%orie
.. So)ato%eni# &ain i &ain 4ith #a" e 5" "all! kno4n6 lo#ali e$ in the (o$! ti "e a7 no#i#e&ti+e &ain (7 ne"ro&ati# &ain 0. P !#ho%eni# &ain i &ain for 4hi#h there i no kno4n &h! i#al #a" e ("t &ro#e in% of en iti+e infor)ation in 3NS i $! t"r(e$
A#"te an$ #hroni# &ain A#"te &ain i a &rote#ti+e )e#hani ) that alert the in$i+i$"al to a #on$ition or e*&erien#e that i i))e$iatel! har)f"l to the (o$! On et - " "all! "$$en

8elief / after the #he)i#al )e$iator that ti)"late the no#i#e&tor , are re)o+e$ ' Thi t!&e of &ain )o(ili e the in$i+i$"al to &ro)&t a#tion to relief it ' Sti)"lation of a"tono)i# ner+o" ! te) #an (e o( er+e$ $"rin% thi t!&e of &ain #!ydria"i", tachycardia, tachypnoe, "$eating, va"ocon"triction% 8e &on e to a#"te &ain / in#rea e$ heart rate / in#rea e$ re &irator! rate / ele+ate$ (loo$ &re "re / &allor or fl" hin%, $ilate$ &"&il / $ia&hore i / (loo$ "%ar / %a tri# a#i$ e#retion / %a tri# )otilit! / (loo$ flo4 to the +i #era, ki$ne! an$ kin / na" ea o##a ionall! o##"r

P !#holo%i#al an$ (eha+io"ral re &on e to a#"te &ain - fear / %eneral en e of "n&lea antne / an*iet! or "nea e

3hroni# &ain i &er i tent or inter)ittent " "all! $efine$ a la tin% at lea t 9 )onth The #a" e i often "nkno4n, often $e+elo& in i$io" l!, +er! often i a o#iate$ 4ith a en e of ho&ele ne . De&re ion often re "lt ne an$

hel&le

P !#holo%i#al re &on e to #hroni# &ain Inter)ittent &ain &ro$"#e a &h! iolo%i# re &on e i)ilar to a#"te &ain. Per i tent &ain allo4 for a$a&tation 5f"n#tion of the (o$! are nor)al ("t the &ain i not reliefe$6 3hroni# &ain &ro$"#e & !#holo%i#al #han%e The )ain #han%e are/ $e&re ion / an atte)&t to kee& &ain / relate$ (eha+io"r to a )ini)") / lee&in% $i or$er / &reo##"&ation 4ith the &ain / ten$en#! to $en! &ain i%nifi#ant (eha+io"ral an$

Pain thre hol$ an$ &ain toleran#e

The &ain thre hol$ i the &oint at 4hi#h a ti)"l" i &er#ei+e$ a &ain It $oe not +ar! i%nifi#antl! a)on% health! &eo&le or in the a)e &er on o+er ti)e Per#e&t"al $o)inan#e/ inten e &ain at one lo#ation )a! #a" e an in#rea e in the &ain thre hol$ in another lo#ation ' The &ain toleran#e i e*&re o+ert &ain re &on e . It i infl"en#e$ (! / &er on #"lt"ral &re #ri&tion / e*&e#tation / role (eha+io"r / &h! i#al an$ )ental health e$ a $"ration of ti)e or the

inten it! of &ain that an in$i+i$"al 4ill en$"re (efore initiation

' Pain toleran#e i %enerall! $e#rea e$/ 4ith re&eate$ e*&o "re to &ain, / (! fati%"e, an%er, (ore$o), a&&rehen ion, / lee& $e&ri+ation ' Toleran#e to &ain )a! (e in#rea e$/ (! al#ohol #on ")&tion, / )e$i#ation, h!&no i , / 4ar)th, $i tra#tin% a#ti+itie , / tron% (elief or faith

Pain toleran#e +arie %reatl! a)on% &eo&le an$ in the a)e &er on o+er ti)e A $e#rea e in &ain toleran#e i al o e+i$ent in the el$erl!, an$ 4o)en a&&ear to (e )ore tolerant to &ain than )en

A%e an$ &er#e&tion of &ain

3hil$ren an$ the el$erl! )a! e*&erien#e or e*&re $ifferentl! than a$"lt Infant in the fir t . to 0 $a! of life are le en iti+e to &ain &ain

5or the! i)&l! la#k the a(ilit! to +er(ali e the &ain e*&erien#e6. A f"ll (eha+io"ral re &on e to &ain i a&&arent at 1 to .0 )onth of life Ol$er #hil$ren, (et4een the a%e of .: an$ .; !ear , ten$ to ha+e a lo4er &ain thre hol$ than $o a$"lt Pain thre hol$ ten$ to in#rea e 4ith a%ein% Thi #han%e i &ro(a(l! #a" e$ (! &eri&heral ne"ro&athie an$ #han%e in the thi#kne of the kin

Ne"roanato)! of &ain
The &ortion of the ner+o" ! te) re &on i(le for the en ation an$ &er#e&tion of &ain )a! (e $i+i$e$ into three area .. afferent &ath4a! 0. 3NS 1. efferent &ath4a! The afferent &ortion i #o)&o e$ ofa6 no#i#e&tor 5&ain re#e&tor 6 (6 afferent ner+ fi(re #6 &inal #or$ net4ork

 Afferent &ath4a! ter)inate in the $or al horn of the

&inal #or$ 5. t afferent ne"ron6 < 0n$ afferent ne"ron #reate ! te) &inal &art of afferent

The &ortion of 3NS in+ol+e$ in the inter&retation of the &ain i%nal are the li)(i# ! te), reti#"lar for)ation, thala)" , h!&othala)" an$ #orte* The efferent &ath4a! , #o)&o e$ of the fi(er #onne#tin% the reti#"lar for)ation, )i$(rain, an$ "( tantia %elatino a, are re &on i(le for )o$"latin% &ain en ation

The (rain fir t &er#ei+e the en ation of &ain

' The thala)" , en iti+e #orte* &er#ei+in% $e #ri(in% lo#ali in% of &ain

' Part of thala)" , (rain te) an$ reti#"lar for)ation/ i$entif! $"ll lon%er/la tin%, an$ $iff" e &ain

' The reti#"lar for)ation an$ li)(i# ! te)/ #ontrol the e)otional an$ affe#ti+e re &on e to &ain =e#a" e the #orte*, thala)" an$ (rain te) are inter#onne#te$ 4ith the h!&othala)" an$ a"tono)i# ner+o" ! te), the &er#e&tion of &ain i a o#iate$ 4ith an a"tono)i# re &on e

The role of the afferent an$ efferent &ath4a! in &ro#e in% of &ain infor)ation
No#i#e&ti+e &ain
No#i#e&tor - >n$in% of )all "n)!elinate$ an$ li%htl! )!elinate$ afferent ne"ron Sti)"lator 3he)i#al, )e#hani#al an$ ther)al no*ae Mil$ ti)"lation &o iti+e, &lea "ra(le en ation 5e.%. ti#klin%6 Stron% ti)"lation &ain The e $ifferen#e are a re "lt of the fre,"en#! an$ a)&lit"$e of the afferent i%nal tran )itte$ fro) the ner+e en$in% to the 3NS In )" #le , ten$on , e&i$er)i , "(#"tano" ti +i #eral or%an - the! are not e+enl! $i tri("te$ in the (o$!
5in kin )ore then in internal tr"#t"re %

Lo#ation-

"e,

No#i#e&ti+e &ain- )e#hani ) in+ol+e$ in $e+elo&)ent

Afferent &ath4a! ' Fro) no#i#e&tor tran )itte$ (! )all A/$elta fi(er an$ 3/ fi(er to the &inal #or$ for) !na& e 4ith ne"ron in the $or al horn5DH6 ' Fro) DH tran )itte$ to hi%her &art of the &inal #or$ an$ to the re t of the 3NS (! &inothala)i# tra#t ?The )all "n)!elinate$ 3/ ne"ron are re &on i(le for the tran )i ion of $iff" e ("rnin% or a#hin% en ation ?Tran )i ion thro"%h the lar%er, )!elinate$ A/ $elta fi(er o##"r )"#h )ore ,"i#kl!. A / fi(er #arr! 4ell/lo#ali@e$, har& &ain en ation

>fferent anal%e i# ! te)

It role- / inhi(ition of afferent &ain i%nal Me#hani ) / &ain afferent ti)"late the ne"ron in &eria,"e$"#tal %ra! #PAG6 / %ra! )atter "rro"n$in% the #ere(ral a,"e$"#t in the )i$(rain re "lt in a#ti+ation of efferent 5$e #en$ent6 anti/no#i#e&ti+e &ath4a! - fro) there the i)&"l e are tran )itte$ thro"%h the &inal #or$ to the $or al horn - there tha! inhi(it or (lo#k tran )i i%nal at the le+el of $or al horn ion of no#i#e&ti+e

>nk B enkefaliner%i# PAG B &araa,"e$"#tal %ra! >AA B e*#itator! a)ino a#i$ 8CM B ro tral +entro/)e$ial )e$"lla

De #en$ent antino#i#e&ti+e ! tA)

The role of the &inal #or$ in &ain &ro#e

&inal e%)ent that the! enter. So)e, ho4e+er, e*ten$ to4ar$ the hea$ or the foot for e+eral e%)ent (efore ter)inatin%

in%

' Mo t afferent &ain fi(er ter)inate in the $or al horn of the

' The A/ fi(er , o)e lar%e A/$elta fi(er an$ )all 3/ fi(er ter)inate in the la)inae of $or al horn an$ in the "( tantia %elatino a ' The la)inae than tran )it &e#ifi# infor)ation 5a(o"t ("rne$ or #r" he$ kin, a(o"t %entle &re afferent ne"ron "re6 to 0n$

' 0n$ afferent ne"ron tran )it the i)&"l e fro) the "( tantia %elatino a 5SG6 an$ la)inae thro"%h the +entral an$ lateral horn, #ro in% in the a)e or a$Da#ent &inal e%)ent, to the other i$e of the #or$. Fro) there the i)&"l e i #arrie$ thro"%h the &inothala)i# tra#t to the (rain. The t4o $i+i ion of &inothala)i# tra#t are kno4n.. the neo &inothala)i# tra#t - it #arrie infor)ation to the )i$ (rain, thala)" an$ &o t #entral %!r" 54here &ain i &er#ei+e$6 0. the &aleo &inothala)i# tra#t - it #arrie infor)ation to the reti#"lar for)ation, &on , li)(i# ! te), an$ )i$ (rain 5)ore !na& e to $ifferent tr"#t"re of (rain6

PAG B &eria,"e$"#tal %ra! P= B &ara(ra#hial n"#le" in &on CM&o B +entro)e$ial &art of the &o terior n"#lear #o)&le* MD+# B +entro#a"$al &art of the )e$ial $or al n"#le" CPL B +entro&o terior lateral n"#le" A33 B anterior #in%"late #orte* P33 B &o terior #in%"late #orte* HT B h!&othala)" S., S0 B fir t an$ e#on$ o)ato en or! #orti#al area PP3 B &o terior &arietal #o)&le* SMA B "&&le)entar! #orti#al area AMYG B a)!%$ala PF B &refrontal #orte*

Theor! of &ain &ro$"#tion an$ )o$"lation

& Mo t rational e*&lanation of &ain&ro$"#tion an$ )o$"lation i (a e$ on %ate #ontrol theor! #created by Mel'ac( and )all% & A##or$in% to thi theor!, no#i#e&ti+e i)&"l e are tran )itte$ to the &inal #or$ thro"%h lar%e A/ $elta an$ )all 3/ fi(er & The e fi(er #reate !na& e in the SG & The #ell in thi tr"#t"re f"n#tion a a %ate, re%"latin% tran )i ion of i)&"l e to 3NS Sti)"lation of lar%er ner+e fi(er 5A/alfa, A/(eta6 #a" e the #ell in SG to E#lo e the %ateE. ' A #lo e$ %ate $e#rea e ti)"lation of T/#ell 5the 0n$ afferent ne"ron6, 4hi#h $e#rea e tran )i ion of i)&"l e , an$ $i)ini he &ain &er#e&tion

Sti)"lation of )all fi(er in&"t inhi(it #ell in SG an$ Eo&en the %ateE. & An o&en %ate in#rea e the ti)"lation of T/#ell tran )i ion of i)&"l e enhan#e &ain &er#e&tion & In a$$ition to %ate #ontrol thro"%h lar%e an$ )all fi(er ti)"lation, the #entral ner+o" ! te), thro"%h efferent &ath4a! , )a! #lo e, &artiall! #lo e, or o&en %ate. 3o%niti+e f"n#tionin% )a! th" )o$"late &ain &er#e&tion

A#tion of en$or&hin 5>D6

All >D a#t (! atta#hin% to o&iate re#e&tor on the &la )a )e)(rane of the afferent ne"ron. The re "lt than i inhi(ition of relea in% of the ne"rotran )itter, th" (lo#kin% the tran )i ion of the &ainf"l ti)"l"

Ne"ro&athi# &ain
It o##"r
ner+o" a a re "lt of inD"r! to or $! f"n#tion of the ! te) it elf, &eri&heral or #entral

Deaferentation &ain - for) of ne"ro&athi# &ain- a ter) i)&l!in% that en or! $efi#it in the &ainf"l area i a &ro)inent feat"re #ane the ia $oloro a% ' Phanto) &ain/ &ain lo#ali@ei into non/e*i tin% or%an 5ti ' Lon%/la tin% &ain after hort/la tin% &ain ti)"l" "e6

Fhat #a" e ne"ro&athi# &ainG

*europathic pain o ten "ee!" to have no obviou" cau"e; but, "o!e co!!on cau"e" o neuropathic pain include: +lcoholi"!, +!putation, ,ac(, Leg, and -ip proble!", .he!otherapy, /iabete" !ellitu", 0acial nerve proble!", -IV in ection or +I/1 Multiple "clero"i", 1hingle" #-erpe" yo"ter%, 1pine "urgery

Fhat are the !)&to) of ne"ro&athi# &ainG

1y!pto!" !ay include: 1hooting and burning pain, Tingling and nu!bne""

' H!&er en iti+it! B increa"ed "en"itivity o the "y"te!

involved in the pain proce""ing

' H!&eral%e ia B increa"ed the pain "en"itivity to no2iou"

"ti!uli

Allo$!nia - pheno!enon characteri"ed by pain ul

"en"ation" provo(ed by non-no2iou" "ti!uli, #e.g. touch%, tran"!itted by a"t- conducting nerve ibre"

Me#hani )- change" o the re"pon"e characteri"tic" o "econd - order "pinal neuron" "o that nor!ally inactive or $ea( "ynaptic contact !ediating non-no2iu" "ti!uli acquire the capability to activate a neuron that nor!ally re"pond" only to i!pul"e" "ignaling pain

Peri&heral ne"ral%ia after tra")a or "r%er!

3o))on for) of ne"ro&athi# &ain

l")(o

a#ral an$ #er+i#al rhi@oto)!, < &eri&heral ne"ral%ia

Mo t &eri&heral ne"ral%ia are the re "lt of tra")a or "r%er!. S"#h a #on$ition $oe not ne#e #a" e$ (! an in#i ion in+ol+in% onl! 5in#i ional &ain6 Me#hani ): the &ain i $"e to ne"ro)a for)ation in the #ar ti "e 5G6 ar! o##"r a a re "lt of $a)a%ein% a )aDor ner+e tr"nk ("t )a! (e )all ner+e (ran#he

Deaferentation &ain follo4in% &inal #or$ inD"r!

In#i$en#e of
e+ere &ain $"e to &inal #or$ an$ #a"$a e,"ina le ion ran%e fro) 1: to H0 I of &atient

Thi &ain i a #ri(e$ to 1 #a" e : .. )e#hani#all! in$"#e$ &ain 5fra#t"re (one , )!ofa #ial &ain6 0. ra$i#"lar &ain 5#o)&re ion of ner+e root6

1. #entral &ain 5$eaferentation )e#hani )6

3lini#al Manife tation of Pain A#"te Pain

Fe #an $i tin%"i h t4o t!&e of a#"te &ain: .. So)ati# 0. Ci #eral B referre$
So)ati# &ain i "&erfi#ial #o)in% fro) the kin or #lo e to the "rfa#e of the (o$!. Ci #eral &ain refer to &ain in internal or%an , the a($o)en, or #he t. 8eferre$ &ain i &ain that i &re ent in an area re)o+e$ or $i tant fro) it &oint of ori%in. The area of referre$ &ain i "&&lie$ (! the ner+e fro) the a)e &inal e%)ent a the a#t"al ite of &ain.

Different t!&e of #hroni# o)ati# &ain

I. Ner+o" ! te) inta#t .. no#i#e&ti+e &ain 0. no#i#e&ti+e / ne"ro%eni# &ain 5ner+e tr"nk &ain6 II. Per)anent f"n#tional an$7or )or&holo%i#al a(nor)alitie of the ner+o" ! te) 5&re%an%lioni#, &inal / "&ra &inal6 .. ne"ro%eni# &ain 0. ne"ro&athi# &ain 1. $eafferentation &ain

The )o t #o))on #hroni# &ain

.. Per i tent lo4 (a#k &ain
B re "lt of &oor )" #le tone,ina#ti+it!, )" #le train, "$$en +i%oro" e*er#i e

0. 3hroni# &ain a

o#iate$ 4ith #an#er

1. Ne"ral%ia - re "lt fro) $a)a%e of &eri&heral ner+e

a6 3a" al%ia - e+ere ("rnin% &ain a&&earin% . to 0 4eek after the ner+e inD"r! a o#iate$ 4ith $i #oloration an$ #han%e in the te*t"re of the kin in the affe#te$ area. (6 8efle* !)&atheti# $! tro&hie - o##"r after &eri&heral ner+e inD"r! an$ i #hara#teri e$ (! #ontin"o" e+ere ("rnin% &ain. Ca o)otor #han%e are &re ent 5+a o$ilatation +a o#on tri#tion #ool #!anoti# an$ e$e)ato" e*tre)itie 6. #ial &ain !n$ro)e - e#on$ )o t #o))on #a" e of #hroni# &ain. The"e condition" include: )!o iti , fi(ro iti , )!al%ia, )" #le train, inD"r! to the )" #le an$ fa #ia The pain i" a re"ult o )" #le &a ), ten$erne an$ tiffne

J. M!ofa

:. He)ia%no ia
B i a lo of a(ilit! to i$entif! the or#e of &ain on one i$e 5the affe#te$ i$e6 of the (o$!. A&&li#ation of &ainf"l ti)"li to the affe#te$ i$e th" &ro$"#e an*iet!, )oanin%, a%itation an$ $i tre ("t no atte)&t to 4ith$ra4al fro) or &" h a i$e the offen$in% ti)"l" . >)otional an$ a"tono)i# re &on e to the &ain )! (e inten ifie$. 3 He)ia%no ia i a affe#te$ i$e o#iate$ 4ith troke that &ro$"#e

&aral! i an$ h!&er en iti+it! to &ainf"l ti)"li in the

9. Phanto) li)( &ain - i &ain that an in$i+i$"al feel in

a)&"tate$ li)(

Patho&h! iolo%! of )" #le &ain

M" #le &ain / a &art of o)ati# $ee& &ain,
5MP6 / it i #o))on in rhe")atholo%! an$ &ort )e$i#ine / i rather $iff" e an$ $iffi#"lt to lo#ate MP i not a &ro)inent feat"re of the erio" &ro%re i+e $i ea e

affe#tin% )" #le, e.%. the )" #"lar $! tro&hie , $ener+ation , or )eta(oli# )!o&athie , ("t it i a feat"re of rha($o)!ol! i M" #le are relati+el! in en iti+e to &ain 4hen eli#ite$ (! nee$le &ri#k or knife #"t, ("t o+erl!in% fa #ia i +er! en iti+e to &ain. >+ent , &ro#e e 4hi#h )a! lea$ to )" #"lar &ain are3 )eta(oli# e+ent & )eta(oli# $e&letion 5 ATP )" #"lar #ontra#t"re6 & a##")"lation of "n4ante$ )eta(olitie 5KL, (ra$!kinin6

Patho&h! iolo%! of +i #eral &ain

Ci #eral &ainT!&e / an%ina &e#tori , )!o#ar$ial infar#tion, a#"te &an#reatiti , #e&hali# &ain, &ro tati# &ain, ne&hrlol!tiati# &ain 8e#e&tor - "n)!elinate$ 3 / fi(re For h")an &atho&h! iolo%! the kin$ of ti)"li a&t to in$"#e &ain in the +i #era are i)&ortant. It i 4ell/kno4n that the ti)"li likel! to in$"#e #"taneo" &ain are not al%o%eni# in the +i #era. Thi e*&lain 4h! in the &a t the +i #era 4ere #on i$ere$ to (e in en iti+e to &ain

A$e,"ate ti)"li of in$"#in% +i #eral &ain.. a(nor)al $i tention an$ #ontra#tion of the hollo4 +i #era )" #le 4all 0. ra&i$ tret#hin% of the #a& "le of "#h oli$ +i #eral or%an a are the li+er, &leen, &an#rea ... 1. a(r"&t ano*e)ia of +i #eral )" #le J. for)ation an$ a##")"lation of &ain / &ro$"#in% "( tan#e :. $ire#t a#tion of #he)i#al ti)"li 5oe o&ha%" , to)a#h% 9. tra#tion or #o)&re M. infla))ator! &ro#e ion of li%a)ent an$ +e e el

;. ne#ro i of o)e tr"#t"re 5)!o#ar$i"), &an#rea 6

3hara#teri ti# feat"re of tr"e +i #eral &ain

a6 it i $"ll, $ee&, not 4ell $efine$, an$ $ifferentl! $e #ri(e$ (! the &atient (6 o)eti)e it i $iffi#"lt to lo#ate thi t!&e of &ain (e#a" e it ten$ to irra$iate #6 it i often a##o)&anie$ (! a en e of )alai e $6 it in$"#e tron% a"tono)i# refle* &heno)ena 5)"#h )ore &rono"n#e$ than in &ain of o)ati# ori%in6 / $iff" e 4eatin%, +a o)otor re &on e , #han%e of arterial &re "re an$ heart rate, an$ an inten e & !#hi# alar) rea#tion /Ean%or ani)iE / in an%ina &e#tori 6 ' There are !any vi"ceral "en"ation that are unplea"ant but belo$ the level o pain, e.g. eeling o di"agreeable ullne"" or acidity o the "to!ach or unde ined and unplea"ant thoracic or abdo!inal "en"ation. The"e vi"ceral "en"ation !ay precede the on"et o vi"ceral pain

8efere$ +i #eral &ain 5tran ferre$ &ain6

8efere$ &ain 4 $hen an algogenic proce"" a ecting a vi"cu" recur"
requently or beco!e" !ore inten"e and prolonged, the location beco!e" !ore e2act and the pain ull "en"ation i" progre""ively elt in !ore "uper icial "tru ture" 3 8efere$ &ain )a! (e a##o)&anie$ (! allo$!nia an$ #"taneo" an$ )" #"lar h!&eral%e ia

Me#hani ) in+ol+e$ in refere$ &ain #reationa6 #on+er%en#e of i)&"l e fro) +i #era an$ fro) the kin in the 3NS 1en"ory i!pul"e" ro! the vi"cera create an irritable ocu" in the "eg!ent at $hich they enter the "pinal cord. + erent i!pul"e" ro! the "(in entering the "a!e "eg!ent are thereby acilitated, giving ri"e to true cutaneou" pain. (6 en@iti@ation of ne"ron in $or al horn

 Painf"l +i
refle*e 6

#eral afferent i)&"l e a#ti+ate anterior horn

)otor #ell to &ro$"#e ri%i$it! of the )" #le 5+i #ero)otor

A i)ilar a#ti+ation of anterolateral a"tono)i# #ell in$"#e

&!loere#tion, +a o#on tri#tion, an$ other !)&atheti# &heno)ena The"e !echani"!", $hich in !odern ter!" can be de ined a" po"itive "y!pathetic and !otor eedbac( loop", are unda!ental in re ered pain

It i #lear that &ainf"l ti)"lation of +i #eral tr"#t"re e+oke a +i #ero)" #"lar refle*, o that o)e )" #le #ontra#t an$ (e#o)e a ne4 o"r#e of &ain

 It ha

(een o( er+e$ that the lo#al ane theti# (lo#k of the

!)&atheti# %an%lia le$ to the $i a&&earan#e, or at lea t to a )arke$ $e#rea e, of reffere$ &ain, allo$!nia, h!&eral%e ia.

In

o)e #on$ition , reffere$ o)ati# &ain i lon%/la tin%, i+el!, an$ i a##o)&anie$ (! $! tro&h!

in#rea e &ro%re

of o)ati# tr"#t"re . 5o""ible !echani"!": - on"et o "el -!aintaining +i#io" #ir#le i!pul"e": peripheral ti""ue a erent iber" central nervou" "y"te!

peripheral ti""ue "o!atic and "y!pathetic e erent ibre"

 Intri#ate #on$ition - in "o!e type" o pain, e.g. che"t pain, i" di icult to di"tingui"h the true cau"e o pain becau"e "uch (ind o pain !ay be related to cervical o"teoarthro"i", e"ophageal hernia, or cholecy"titi". It i" di cult to a"certain $hether the"e intricate condition" are due to a "i!ple addition o i!pul"e" ro! di erent "ource" in the .*1 or to "o!atovi"ceral and vi"cero"o!atic re le2 !echani"!". It ha" been de!on"trated that the !ne!onic proce"" i" acilitated i the e2perience to be retained i" repeated !any ti!e" or i" acco!panied by plea"ant or unplea"ant e!otion". 5ain i", at lea"t in part, a learned e2perience - e.g. during the ir"t renal colic, true parietal pain ollo$ed vi"ceral pain a ter a variable interval. In "ub"equent epi"ode" o renal colic pain, parietal pain developed pro!ptly and $a" not preceded by true vi"ceral pain. Thi" i" probably due to the activation o !ne!onic trace".

Silent )!o#ar$ial i #he)ia 5SMI6

< 3he t &ain i onl! a late an$ in#on tant )arker of e&i o$e of tran ient MI in +a o &a ti# an%ina 51N I6, in ta(le an%ina 5:N I6

& Me#hani ) of SMI

a6 La#k of the &ain i , in &art, relate$ to the $"ration an$ e+erit! of MI. >&i o$e horter than 1 )in, an$ tho e a##o)&anie$ (! "re . a )o$e t i)&air)ent of left +entri#le 5 in en$/$ia toli# &re inferior to 9 )) H%6 are al4a! &ainle &ain in o)e in tan#e ("t not in other

Lon%er an$ )ore e+ere e&i o$e are a###o)&anie$ (! #he t

(6 Pa#ient 4ith &re$o)inantl! SMI a&&ear to ha+e a %enerali@e$ $efe#ti+e &er#e&tion of &ain 5 thre hol$ an$ toleran#e6. Me#hani ): le+el of #ir#"latin% /en$or&hin 5G6

Di t"r(an#e in &ain &er#e&tion an$ no#i#e&tion

Mo t of the $i t"r(an#e are #on%enital a6 3on%enital anal%e ia - no#i#e&ti+e ti)"li are not &ro#e e$ an$7or inte%rate$ at a le+el of (rain. Patient $oe not feel a &ain (6 3on%enital en ori# ne"ro&ath! - no#i#e&ti+e ti)"li are not tran )itte$ (! &eri&heral ner+e or (! &inal afferent tra#t . A#,"ire$ $i t"r(an#e in &ain &er#e&tion an$ no#i#e&tion The! )a! o##"r at !rin%o)!el!, $i t"r(an#e of &arietal lo(e of (rain, in &atient "fferin% fro) ne"ro&ath! 5e.%. #hroni# $ia(ete )ellit" 6