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&GTP + 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