ITCH

PATHOPHYSIOLOGY
Ninik Sukartini
Clinical Pathology Dept. FMUI

INTRODUCTION
Itch is the principal symptom
of skin disease and is an
important skin manifestation
of systemic disease.
How does scratching
temporarily relieve itch ?

introduction
Classification of itch :
Pruritoceptive : generated in the skin usually
by an inflammatory or other visible pathological
process eg scabies, urticaria
Neurogenic : generated in the CNS in response
to circulating pruritogens as in cholestasis
Neuropathic : due to anatomical lesions of the
central or peripheral nervous systems eg nerve
entrapment, tumour
Psychogenic : including delusional parasitosis

Itch receptors
Epidermis (especially keratinocytes)
constitute the itch receptor
Keratinocytes express a range of
neuropeptide mediators and receptors
which involved in pruritus
Mediators : opioids, nerve growth factor
(NGF), substance P
Receptors: vanilloid receptors, proteinase
activated receptor type 2 (PAR2), voltagegated ATP channel

Neural pathway for itch

Slow-conducting unmyelinated C neurons
which only transmit itch (and temperature
changes) in response to histamine
Represent only about 5 % of total neurons
Selectively activated in the chronic pruritic
skin disease
Contralateral transmission neurons,
consist of an itch-specific subclass of lamina 1
spinothalamic tract neurons, convey itch to
the thalamus

Regulation of itch
Inhibitory neuronal circuit located in the
substantia gelatinosa of the posterior horns of
spinal cord a gated mechanism whereby
afferent itch can be regulated
Increased tone in descending pathway results
from visual, auditory and other stimuli
activation of inhibitory neuronal circuit closure
of the gated mechanism diminished itch traffic
reason during daytime, itch is less
troublesome
Result of an imbalance between opioid actions
on central (increasing itch) and (diminishing
itch) receptors

Mediators of itch
Cross-talk between C neuron terminals and
the spatially closely related dermal mast
cells
Histamine
Eicosanoids
ligates H1 receptors associated
TNF-
with C neuron
Tryptase activate PAR2 expressed on afferent
C neuron terminals stimulates itch sensation
& triggers release of substance P further
mast cell activation

Mediators of itch
Neurotrophins (NGF) causes
proliferation of unmyelinated
afferent nerve terminals,
sensitisation of afferent nerve
terminals and increased expression
of neuropeptides
Keratinocytes express high level of
NGF
High urinary and plasma level of NGF
found in patient with atopic eczema

How does scratching temporarily relieve itch ?

Scratching activates thickly

myelinated fast-conducting A
neurons widespread surround
inhibition to activation of the
Inhibitory neuronal circuit

Itch of cholestasis
Opioids cause intense pruritus
Biliary obstruction leads to increased
intrahepatic synthesis of opioid
peptides which spill over in to the
circulation and cause pruritus by
acting on -opioid receptors in
central nervous system

Thank you