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REVIEW ARTICLE
Itch and brain
Hideki MOCHIZUKI,1 Ryusuke KAKIGI2
1
Department of Dermatology, Temple University School of Medicine, Temple Itch Center, Philadelphia, Pennsylvania, USA,
2
Department of Integrative Physiology, National Institute for Physiological Sciences, Okazaki, Japan
ABSTRACT
Itch is an unpleasant somatic sensation that evokes the urge to scratch. Chronic itch is a severe problem that
diminishes quality of life. There are many patients suffering from chronic itch across the world. The brain is the
final terminal to receive itch-related signals from the body and plays an important role in perceiving the itch sen-
sation. Thus, to understand the cerebral mechanism of itch perception and how this mechanism differs between
healthy subjects and chronic itch patients is important for advancing our understanding on the pathophysiology
of chronic itch. Itch is suppressed by scratching or applying painful stimuli. The pleasurable sensation evoked by
scratching an itch increases the urge to scratch. Viewing others in itch or imagining the itch sensation may evoke
real itch sensations and the scratching response. To understand the mechanisms responsible for these phenom-
ena may provide useful information for the development of treatment of itch and advance our understanding of
the cerebral mechanism of itch and scratch. Several functional brain imaging studies have addressed these
issues and reported interesting findings. In this review article, the authors discussed the findings of previous
studies and how they have advanced our understanding of the central mechanisms of itch, scratch and chronic
itch.
Key words: cerebral response to itch, contagious itch, functional brain imaging, itch suppression,
pleasurability derived from scratching.
Correspondence: Hideki Mochizuki, Ph.D., Department of Dermatology, Temple University School of Medicine, Temple Itch Center, 3322 North
Broad Street, Suite 212, Philadelphia, PA 19140, USA. Email: hideki.mochizuki@tuhs.temple.edu
Received 14 April 2015; accepted 16 April 2015.
CONTAGIOUS ITCH
The itch sensation may be evoked simply by discussing a topic
associated with itch or viewing others in itch. Niemeier et al.61
investigated whether scratching behavior was evoked in those
Figure 3. The anatomical location of the insular cortex and situations. Two different conditions were used: an itch-inducing
basal ganglia. The anterior part of the insular cortex (aIC), pos- lecture including pictures of insects, scratch marks and allergic
terior part of the insular cortex (pIC) and basal ganglia (BG) are reactions, while the other condition focused on relaxation. They
shown in the transverse view of the brain template imple- found that scratching behavior was more robust during the
mented in the MRIcron software (http://www.mccauslandcen- itch-inducing lecture than during the relaxation lecture. Other
ter.sc.edu/mricro/).
studies reported similar findings.62,63 Two previous studies
investigated the cerebral mechanism underlying contagious
and legs in certain directions.49–53 The itch sensation may itch using fMRI,64,65 and demonstrated that several brain
induce similar mental processes such as directing attention to regions including the IC, SMA, PM and prefrontal cortex were
the itchy skin caused by the desire to scratch. This mental activated while viewing others experiencing the itch sensation.
component may be associated with activation of the precu- Moreover, it was reported that functional connectivity between
neus during itch stimuli. Further studies are needed in order to the IC and basal ganglia significantly increased during imagery
elucidate the role of this region in itch perception. of itch.65 The IC is associated with emotional processing, while
the basal ganglia is associated with the motivation to act. This
functional coupling may play an important role in triggering
CEREBRAL RESPONSE TO ACUTE ITCH IN
scratching response or urge to scratch by viewing others in
CHRONIC ITCH PATIENTS
itching and the imagery of itch.
Chronic itch is associated with several medical conditions
including dermatological, systemic, neurological and psycho-
ITCH SUPPRESSION AT THE SPINAL AND
genic diseases, and is idiopathic in many cases.54 It affects
SUPRASPINAL LEVEL
millions of people worldwide, and is considered a global health
problem.55–58 Severe itch and pathological scratching behavior The itch sensation is suppressed by applying counter stimuli
represent significant problems for chronic itch patients, dimin- including painful and scratching stimuli. A previous study
ishing their quality of life. However, only a few functional brain reported that itch suppression was observed even though
imaging studies have been conducted on these patients. Two these counter stimuli were applied far from the itchy site.66
studies previously investigated similarities and differences in This finding suggested that the central nervous system may
brain activation patterns associated with itch between patients also be associated with itch suppression, and was subse-
with atopic dermatitis and healthy subjects.8,28 These studies quently investigated by animal studies.67,68 These animal stud-
reported an abnormality in the basal ganglia of chronic itch ies recorded neural activity from the spinal cord when animals
patients (Fig. 3). One study reported significantly higher activity perceived the itch sensation and observed that the neural
in the basal ganglia for patients with atopic dermatitis, while activity associated with itch was suppressed during and after
scratching. Akiyama et al.68 reported that scratching was 50% the itch sensation. An fMRI study indicated that acupuncture-
less effective in reducing neuronal firing after transection of the induced itch relief was associated with the modulation of itch-
upper cervical spinal cord, and that scratching still reduced related neural activity, in particular in the putamen.72
neuronal firing (by 24%), but to a lesser degree than before
transection. This finding demonstrated that top-down modula-
PLEASURE OF SCRATCHING AND THE
tion from the supraspinal level played a major role in itch sup-
REWARD SYSTEM
pression. A human PET study speculated that an activation of
descending pathway from the periaqueductal gray matter Scratching suppresses the itch sensation. At the same time, it
(PAG) may induce itch relief in humans.26 Carstens69 reported evokes a pleasurable sensation. Pleasure is one of the factors
that excitation of the PAG inhibited the neural firing associated to reinforce and motivate this behavior. Thus, this pleasurable
with itch at the spinal level. The descending inhibitory pathway sensation may induce excessive scratching. However, it cur-
from the PAG70 may be associated with the itch suppression rently remains unclear why scratching an itch is pleasurable
(Fig. 2). By contrast, an fMRI study reported deactivation of and can induce excessive scratching. Two fMRI studies inves-
the PAG during scratching.71 Based on this finding, this study tigated these issues.23,71 One study reported that activity in the
suggested that an opposite effect operates in itch modulation reward system including the striatum and midbrain was signifi-
during scratching. That is, deactivation of the PAG may be a cantly higher when the pleasurable sensation was evoked by
key factor in itch modulation by scratching. A more detailed scratching than when the pleasurable sensation was not
investigation is needed in order to clarify whether the PAG is evoked by scratching (Fig. 4c). The other study demonstrated
associated with itch modulation. Acupuncture may also reduce that activity in the reward system while scratching an itch posi-
(a) Pleasant R
(b) Control
IC IFG/PM
Striatum MCC
PM SMA
(c) P>C
Midbrain Thalamus S1
Cb
Figure 4. Brain activity during scratching. (a) Brain activity during scratching itchy skin (pleasant condition). (b) Brain activity during
scratching far from itchy skin (control condition). (c) Brain regions that showed significantly higher activity in the pleasant condition
compared with the control condition (P > C). Cb, cerebellum; IC, insular cortex; IFG, inferior frontal gyrus; MCC, midcingulate cor-
tex; PM, premotor cortex; S1, primary somatosensory cortex; SMA, supplementary motor area.23
tively correlated with the perceived pleasurable sensation.71 these systems in the brain such as the hypothalamus may be
The reward system is the key structure of hedonic experi- associated with stress-induced exacerbation or development of
ences,73–78 suggesting that this system also plays an important chronic itch. Distraction of attention can reduce the itch sensa-
role in scratching-induced pleasurability. The midbrain is rich in tion. An fMRI study have suggested that analgesic effect caused
dopaminergic neurons,79 which send projections to several by distraction of attention is associated with descending inhibi-
areas including the striatum and regulate dopamine levels in tory system.97 The same system may be associated with itch
the innervated areas.79,80 Dopaminergic neurons are activated reduction by distraction of attention. Psychological interventions
by pleasurable stimuli.73,75,77,81–89 Dopamine may be associ- (e.g. relaxation training) is effective for treatment of chronic itch
ated with scratching-induced pleasurability. Previous studies recently.98–101 This important theme should also be addressed in
have observed that motor-related regions such as the SMA, future brain imaging studies.
PM and cerebellum were activated during scratching.10,23
However, subjects did not perform any movement including
CONFLICT OF INTEREST: There is no conflict of interest.
scratching during fMRI measurements in these studies. Thus,
the significant activation of motor-related regions were inde-
pendent of movement. Animal and human studies have dem-
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