dau va thuoc giam dau
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Khp ni thn kinh
t bo thn kinh
m i g c u th v au
u a
AU L MT PHN NG CA SINH VT TRC NHNG TC NHN E DO N S TON VN CA C TH
Cm gic au hnh thnh t 2 yu t chnh: nhn cm au-pain perception- s nhn thc ca v no vi kch thch au ngoi vi. phn ng vi nhn cm au-pain reaction- phn ng ca c th vi nhn cm au m chc nng chnh l gim au nh mt c ch t v.
Nhn cm au c hnh thnh t 2 yu t: vt l & ho hc: Yu t vt l l hot ng in -in th ng - hnh thnh t nhng knh ion K+,Na+ & Ca++. Yu t ho hc l s phng thch cht dn truyn trung gian- cht P- khi pht qu trnh chuyn ho kch hot s nhp bo ca ion Na+ & Ca++ u sng sau cht xm ty. c bit vi ion Ca++ ngoi vic to in th ng cn c th kch hot mt chui phn ng phc tp hy dit t bo. Cm gic au lun lun mang theo mt thng ip- c s ph hy cc b hay lan rng ti mt hay nhiu c quan
IN TH NG: YU T VT L CA CM GIC AU
lung thn kinh c th hnh thnh v dn truyn trn si C t th cm au qua hin tng in th ng vn tc truyn trong khong 4-12m/s.
th cm au, knh K+ chnh lu nhp bo c vai tr rt quan trng trong s khi pht in th ng.
Knh Potassium hi cc sm Knh Potassium hi cc mun
Knh Sodium cm ng in th Knh Calcium cm ng in th Phase 0 ca in th ng l giai on c th ngn chn s hnh thnh cm gic au. Phase 2 c th ngn chn s nhp bo ca Ca++ lm gim cng dn truyn qua synapse.
Ths khau khi im ca cm gic au cm cc-Depolarization- ca th cm au
Si tn cng t do ni tip nhn cm gic au nhit di dng in th ng
+
Cc ion Na+,K+ & Ca++ c th khi pht in th ng ti th cm au
-
TH CM AU Dng K+ nhp bo nng in th ngh n in th bc Nh vy cm gic au c th hnh thnh t in th ng th cm au vI
ION K+.
Phng trnh Nerst tng ng vi tnh trang kch thch cua thu cam au do ion K+ quyet nh nh sau:EMF= - 61 log CKo/Cki
Kenh K+ quyet nh cho trang thai nay la kenh K+ chnh lu nhap baoinward rectifier potassium Tren cac te bao tao nhp channel. cua tim va tren neuron dan truyen cam giac au co Knh K+ chnh lu nhp loai nay. tnh nhieu kenh K+ bo quyt nh
kch thch ca nhiu loi t bo nh m to nhp tim, neuron dn truyn cm gic,c tim. kc khi ngng au h thp do bt k nguyn nhn no.
S CHNH LCH VN TC DN TRUYN CA XUNG THN KINH TRN SI NHIU MYELIN A V SI KHNG MYELIN C. L THUYT KIM SOT CNG CA WALL-MELZACK
12m/s
3om/s
40m/s
Theo l thuyt cng kim sot: -s chnh lch vn tc truyn trn si nhiu Myelin A so vi si C khng Myelin dn ti h qu: to mt in trng c in th >-61mV nhng neuron LTM khng cho php m knh Na+ ca neuron WDR. -nh vy cng khng phi l mt khi nim cu trc hnh th m ch l mt khi nim chc nng (mt in trng-electric field) xut hin khi c 2 loi si A & C b kch thch. -tng ng vi hin tng ny l 2 loi cm gic au: au nhanh (fast pain) & au chm (slow pain). Cm gic au nhanh c tc dng kim sot cng ca cm gic au chm.
Tc ng c ch ca t bo LTM trn t bo WDRTrn si A:c ch qua hin tng in th ng. Trn ng DCIP: c ch qua mt qu trnh chuyn ho c ch phc hp Calcium-Calmodulin & men Adenyl Cyclase do Protein Gi
Si A
ng c ch au hng xung v thuc phin (qua th th & ) cng tc ng trn WDR ngn chn s phng thch cht P
-WDR
LTM
Ngn phng thch cht P
Cn au tht ngc; au thng v, au co tht niu qun ect l nhng v d
au phng chiu-referred pain-cm gic au pht xut t ni tng c th c nhn bit trn mt vng da nng v ngc li do c cng ng dn truyn vo r sau ti mt khoanh ty.
Nhng hin tng l ho ny din tin trn th cm au. Cc cu trc thn kinh sau y to thnh ton b ng dn truyn cm gic au: 1. Th cm au. 2. ng dn truyn au, nng lnh- LATERAL SPINOTHALAMIC TRACT. 3. ng i no-v no THALAMOCORTICAL. 4. V no.
Lateral spinal thalamic
ng cm gac dn truyn cho
Si C
th cm au
V NOTHALAMO-CORTICAL
LATERAL SPINO-THALAMIC
NG DN TRUYN CM GIC AU HNG TM
Si C
NG C CH CM GIC AU V DN TRUYN HNG TM DCIP
Neuron trung gian trong lp II chu tc ng c ch t ng c ch cm gic au hng xung
SNG SAU TY TRM CHUYN TIP GIA TH CM AU NGOI VI VNG DN TRUYN LATERAL SPINO- THALAMIC.
th cm au & u sng sau ty
NEURON P NG PH RNG-WDR
B Lateral Spino-Thalamic
Cht dn truyn thn kinh u sng sau ty l cht Pv tr hot ng ca cht P Neuron WDR va dng cht P nh cht dn truyn khi ng va to ra cht P
Lateral spino thalamic
Si C
Neuron p ng ph rng wide dynamic range-chu s c ch t si A v ng c ch au hng xung
Neuron trung gian ngng kch thch thp-low threshold mecanoreceptive interneuron trong lp II v III chu s kch thch t si A khi tc truyn xung thn kinh gim do thoi ho bao Myeline trn si A& A.
PHNG THCH CHT P-KT IM CA XUNG THN KINH T TH CM AUCa++ CHT P
SI C
WDR
Knh Ca++ cm ng in th & Knh Ca++ l thuc cAMPc vai tr chnh trong cc si C
S huy diet te bao cua Calcium Tien trnh song hanh vi cam giac auCa++
Adenyl cyclaseGiam d tr ATP>P + SR Ca++ + +
PGs
PLC&PLA2 Huy phosph olipids mng
Ty the+ Phosphoryl hoa
proteas eHuy protein khung te bao
+
Tang phong thch Ca++ nuclease Huy nhan
CC CHT HO HC TRUNG GIAN HNH THNH CM GIC AU TI TH CM AUPGE2,F2 HISTAMINE SEROTONINE CHT PACID LACTIC TNF
C CH GY CM GIC AU CA PROSTAGLANDINS
H ngng kch thch ca th cm au bng cch
Tng nhp bo ca ion Ca++ qua knh Calcium l thuc cAMP
Autoreceptor
Ca++
Knh Ca++ l thuc cAMP
th thPhn hy
reuptake
HOT NG BNH THNG CA SYNAPSE
Tng nhp bo Ca++ lm tin cAMP Synapse phng thch Prostaglandins nhiu cht dn Adenyl Cyclase truyn hn
+
Hu Synapse nhn nhiu cht dn truyn hn
Th cm auATP Adenyl cyclase th th prostaglandinAC
prostaglandin
+Protein G
cAMP
Tng nhp bo ion Ca++
Phng thch Ca++ t vng ni bo kch thch Ca++ nhp bo.
Phospholipase C
HISTAMINE
Phospholipase C
HISTAMINE TO CM GIC AU QUA TH TH H1 VI S HNH THNH PGsH1 RECEPTORProtein Gq Protein Gs IP3,DAG cAMP
H2 RECEPTOR
Adenyl Cyclase
Phospholipase A2
PGs
Protein Kinase l thuc Ca ++/Calmodulin
Hnh thnh cm gic au Kch thch c hc/ho hc Thoi ho myeline cc b trn si A&A in th ng thot v Suy gim c ch ti t ty
Phng xung kch pht neuron trung gian ngng kch thch thp (LTM) Phng xung kch pht neuron p ng ph rng (WDR)
Cm gic au
Phn ng vi nhn cm au l mt tin trnh sinh l thn kinh nhm mc ch chnh l gim cng cm gic au.
Tin trnh ny din ra qua ng dn truyn ly tm c tn l NG C CH AU HNG XUNG-DESCENDING INHIBITORY PATHWAY (DCIP).
ch c vai tr trn ng c ch au hng xung ny. Kt qu hot ng ca ng c ch au hng xung thay i trn tng c th do kh nng chu au cng khc nhau trn mi c nhn.
CM GIC AU PHT XUT T NHNG C QUAN THNG GP NHC U
XOANG
TIM& TNG RNG
CT SNG
NIM MC
KHP
AU T XOANG
au t xoang l mt kiu au c trng ca khong chn khng trong xoang-vacuum headache
NHC UPht xut t c quan ni s
Pht xut t mch mu ngoi s nh Migraine
Tin trnh hnh thnh cn Migraine khi u t v no
AU DO THIU MUAcid lactic kch thch th cm au trong vch c
s co tht vch c trn tng p lc trong thnh mch gy thiu mu v chuyn ho ym kh to acid Lactic
AU THT LNGC th do c
Do thot v a m
AU TI NIM MC
MAST CELL
Khi nim mc b tn thng Histamine phng thch t Mast cell c vai tr rt quan trng trong hnh thnh cm gic au
PGs&TNF
NGOI PROSTAGLANDINS, TNF- C TH GP PHN GY AU KHP
THUC GIM AUThuc gim au tuy rt nhiu nhm khc nhau v mt ho hc nhng thc cht ch c nhng c ch tc dng sau1. c ch s tng hp Prostaglandins 2. Ct t s hnh thnh in th ng
3. Ngn chn s phng thch cht P synapse u sng sau ty 4. Phong ta th th TNF- 5. Thuc dn c trn ng mch v tng rng
Thuc c ch tng hp ProstaglandinsC CH COX KHNG CHN LCDn cht acid Salicylic:Aspirin Dn cht Para-amino-Phenol: Acetaminophen Indol v Indene Acetic acid: Indomethacin & Sunlindac Heteroaryl acetic acid: Tolmetin,diclofenac&ketorolac Arylpropionic acid: Ibuprofen, naproxen,oxaprozin Anthranilic acid:mefenamic acid &meclofenamic acid Enolic acic: piroxicam &meloxicam Alkanones:nabumetone
C CH COX CHN LCFuranones :rofecoxib Diaryl-pyrazoles:celecoxib Indol acetic acid: Etodolac Sulfonamides :nimesulide
V TR TC NG CA THUC KHNG PRoSTAGLANDINS
THUC CT T S HNH THNH IN TH NGC CH KNH Ca++carbamazepine
C CH KNH Na+hydantoin carbamazepines H THP IN TH NGH-M KNH Clgabapentin
THUC NGN CHN PHNG THCH CHT P U SNG SAU TUENDORPHINS
OPIUM: Morphine
THUC CHNG TRM CM 3 VNG: imipramine, amitryptiline
v tr xy ra hin tng c chAdenyl cyclase
Tin synapse ca neuron WDRProtein Gi
Cht P C ch hot ng ca thuc phin& cc cht tng t
-
Calmodulin
-
Protein Gi
th th v
Adenyl Cyclase
THUC C CH TNF
infliximab
etanercept
C CH GN KT TNF VO TH TH
Gim au khp do c ch phn ng min dch
THUC TC NG LN C TRNMt s thuc c tc ng trn c trn tuy khng tht s l thuc gim au nhng vn c tc ng tt trong mt s trng hp c bit: Thuc dn mch vnh. Thuc dn c trn tng rng. Thuc khng cholinergic
C
CH
C T
NG
A C
C HU T
N D
C M
NO ngoi sinh H
NH V
Thuc khng cholinergic v thuc khng Ca++ trn c trn c tc ng cui cng ging nhau v cng kim sot nng Ca++ trong bo tng Thuc khng cholinergic: Atropine tc ng trn th th Muscarinic M3
Thuc khng Ca++ trn c trn: Papaverine tc ng c ch nhp bo Ca++ qua knh Calcium loi L
S co c trn
Calcium nhp bo kt hp vI Calmodulin
Myosin p-light chain c tc dng nh troponin
kt hp CaCM vI Myosin light chain kinase
Calcium calmodulin kt hp vI Caldesmon
hot ho Actin Tropomyosin
C trn khng c Troponin
Dy thn kinh Vagus
th th Muscarinic M3
th th M3
T BO C TRNKch thch Phospholipase C Atropine
papaverine Tng cng co c
Tng Phosphatidyl-inositol triphosphate-IP3
KT LUNNhng c ch c trnh by cho thy vic chn thuc gim au khng phc tp Khng bao gi dng thuc gim au n thun (Acetaminophen,dextropropoxyphen, floctafenine ect) trong nhng trng hp c vim Nhng trng hp au ti nim mc, Histamine c mt vai tr kh quan trng v c th gy au gin tip qua s hnh thnh PGs th th H1 Trong trng hp au pht xut t xoang Histamine c th lm gim tnh trng nhc u chn khng
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