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Đau và thuốc giảm đau Đau và thuốc giảm đau tế bào thần kinh tế bào thần kinh Khớp nối thần kinh Khớp nối thần kinh

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&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