PAIN

CHANNELOPATHIES

KRT. Lucas Meliala

Department of Neurology Dr. Sardjito Hospital
Gadjah Mada Faculty of Medicine Yogyakarta
Curriculum Vitae Pendidikan :  Lulus Dokter tahun 1969, alumnus FK-UGM
Nama : Prof. dr. KRT. Lucas Meliala, SpKJ, SpS(K).  Lulus Spesialis Saraf & Jiwa tahun 1974
Tempat/tanggal lahir : Membang Muda (Sumut), alumnus FK-UI, FK-UGM, FK Unair
22 September 1941 Pekerjaan :  Staf Fakultas Kedokteran UGM
Alamat : Jl. Nagan Lor 70, Jogjakarta bagian IP Saraf dan Jiwa sejak
Telepon : (0274) 450758 tahun 1968 sampai sekarang
Fax. : (0274) 374052 Organisasi :  1999-2007 : Ketua Pokdi Nyeri Perdossi
Mobile : 0815 687 0584  Anggota IASP, ENS
E-mail : lucasmeliala@yahoo.com  Ketua Governing board IPS
 PAIN – SERIES OF EVENTS
PERCEPTION

PAIN

MODULATION

TRANSMISSION

TRANSDUCTION
 BRAIN
PEGEL
PERIH
PANAS
PRESSURE

HEAT

CHEMICAL

Modifikasi Meliala, 2003

NOCICEPTORS DENGAN KANAL ION

Mast Cells

Nociceptors
Na+

K+

Receptor activation Ca2+

TrpV1
ASIC
A5-HT2A
P2X3
PGE2
Heat/ BK2
β2 TrkA
capsaicin
NK1

H+
ATP
S-HT
PGE2
BK NGF
Modified Meliala, 2006
Adrenalin SP
 Ca2+

K+
K+

Na+

1. Transduction 3. Propagation
2. Spike Initiation 4. Transmitter Release

Modified Meliala, 2006

 ACTIVATION AND SENSIZITATION
DORSAL HORN NEURONS

SP
Glu
BDNF

NO

PGE2

Na+
Ca2+
NK1 TrkB
Gq/11 Gs NMDA-R AMPA-R

PLC KA-R
AC

IP3 Scr
cAMP
DAG Gs
PKA EP
cAMP AC
PKA
PKC
COX/LOX
PGE2

Increased excitability NOS NO Modified Meliala 2006

Carpenter and Dickenson, 2005

Schematic of Ion Channels in Nociceptor Function

J Clin Irvest, 2010 Nov 1; 120(11): 3745-3752

 STRUCTURE AND FUNCTIONAL
COMPONENTS OF A NOCICEPTOR

David L H Bennett, C Geoff rey Woods, in Painful and painless channelopathies (2014)
Schematic Showing Structural And Functional
Features Of Voltage-Gated Sodium Channels

David L H Bennett, C Geoff rey Woods, in Painful and painless channelopathies (2014)
A simplified cartoon showing the main events
underlying the action potential

Namadurai S, Yereddi NR, Cusdin FS, Huang CL-H, Chirgadze DY, Jackson
AP. 2015 A new look at sodium channel b subunits. Open Biol. 5: 140192.
myelin Na+ K+ Na++

Node of
K+
Aઠ K+ K+ Ranvier

K+ Na+ K+ +
+ Na+ Na+
Na
+ NaNa+ Na +
Na++ Na +
Na+
Na+ Na Na Na
+
Na+

K+ K+
K+ K+
C K+ K+
K+ K+ K+ K+
K+ K+ K+
K+

Modifikasi Meliala, 2003

 Channelopathy

• Merupakan disfungsi kanal ion

• Dapat bersifat genetik maupun dapatan

• Beberapa penyakit dengan channelopathy :

 Epilepsi
 Ataksia
 Migrain
 NYERI
PAIN CHANNELOPATIES

Cregg at All, Pain Channelopaties in J Physiol 588.11 (2010) pp 1897–1904

 The Impact of Channelopathy

 Sensory transduction

 Electrical signaling

 Neurotansmitter release

 Central nervous system function link to

migrains and headache
 Dampak Mutasi Gene

Dalam persepsi nyeri mulai dari tanpa nyeri sampai

Nyeri yang ekstrim

CIP – PEPD - IEM

 The Causes Of Different Pain
Perception In The General
Population May Be Investigated
On These Disease Model.
(CIP , PEPD and IEM).
Persepsi Nyeri Sangat Berbeda Pada Setiap
Individu Dan Channelopathy

Dari Tanpa Nyeri Nyeri Ekstrem

Human Pain Channelopaties

Cregg at All, Pain Channelopaties in J Physiol 588.11 (2010) pp 1897–1904

Clinical Features Of Human Disorders Caused By Mutations
in Ion-channel Genes That Lead To Altered Pain Perception
and Are Inherited In A Mendelian Manner

David L H Bennett, C Geoff rey Woods, in Painful and painless channelopathies (2014)
Example of Heterozygous and Homozygous
Mutation Through Direct Sequencing
a) A TG A GC T T G G A CAGG TG
Normal wild type

b)
AT GA G C T T R G A C A G GTG
Heterozygous

c) AT G A G C T T A G A CA G G TG
Mutant
homozygous
Anger Anxiety

Fear
Depression
A

NOCICEPTIVE

Noxious Stimuli MELIALA, 2004

 “Berbuatlah dan
cintailah tanpa
memperhitungkan
kebahagiaanmu
sendiri, dan
engkau akan
berbahagia
sepanjang waktu”