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INVESTIGATIVE REPORT
Effects of Short-term Temperature Change in the Innocuous Range
on Histaminergic and Non-histaminergic Acute Itch
Zoe LEWIS 1 , David N. GEORGE 1 , Fiona COWDELL 2 and Henning HOLLE 1
Department of Psychology, University of Hull, Hull, and 2 Birmingham City University, Faculty of Health, Education and Life Sciences,
Birmingham, UK
1
While temperatures in the noxious range are well-
known to inhibit acute itch, the impact of temperature
in the innocuous temperature range is less well under-
stood. We investigated the effect of alternating short-
term temperature changes in the innocuous range on
histamine and cowhage-induced acute itch, taking into
account individual differences in baseline skin tempe-
rature and sensory thresholds. Results indicate that
cooling the skin to the cold threshold causes a tem-
porary increase in the intensity of histamine-induced
itch, in line with previous findings. Skin warming in-
creased cowhage-induced itch intensity. Potential
mecha
nisms of this interaction between thermosen-
sation and pruritoception could involve cold-sensitive
channels such as TRPM8, TREK-1 or TRPC5 in the case
of histamine. The rapid modulation of cowhage indu-
ced itch – but not histamine-induced itch – by trans-
ient skin warming could be related to the lower tem-
perature threshold of pruriceptive polymodal C-fibres
(cowhage) as compared to the higher temperature
threshold of the mechanoinsensitive C-fibres convey-
ing histaminergic itch.
Key words: skin temperature; histamine; sensory thresholds;
pruritus.
Accepted Oct 25, 2018; E-published Oct 25, 2018
Acta Derm Venereol 2019; 99: 188–195.
Corr: Dr Henning Holle, Department of Psychology, University of Hull,
Cottingham Road, Hull HU6 7RX, U.K. E-mail: [email protected]
I
t is well documented that thermal counter-stimulation
in the noxious range reduces the intensity of acute itch
(1–4). However, the effect of brief, less extreme changes
of temperature on itch, either by slightly increasing or
decreasing the skin temperature from its baseline tem-
perature of about 32°C, is less well understood. Deter-
mining this relationship is not only of clinical interest,
but also relevant for basic research on itch in humans,
which often requires an experimental itch model where
itch intensity can be quickly modulated (5).
Several studies have investigated the effect of in-
nocuous warmth on experimentally induced acute itch.
Ward et al. (2) induced itch using histamine iontophoresis
and found that warming the skin directly adjacent to
the itch induction site to 38°C using a thermode did not
influence itch intensity. Yosipovitch et al. (4) also used
histamine iontophoresis in combination with a thermode
applied 3 cm distal to the itch induction site, and again
doi: 10.2340/00015555-3077
Acta Derm Venereol 2019; 99: 188–195
SIGNIFICANCE
Determining the influence of temperature changes in the
non-painful range on itch is not only of clinical interest,
but also relevant for basic psychophysical research, which
often requires that itch intensity can be reliably modulated
within a matter of seconds in an on–off fashion. We cha-
racterized the effect of short-term temperature changes on
two types of itch sensations; histamine and cowhage-indu-
ced itch. Our result shows that both itch pathways can be
modulated by short-term changes in temperature, poten-
tially enabling statistically powerful neuroimaging studies,
to further elucidate the cortical network underpinning the
clinically relevant sensation of itch.
found that repeatedly warming the skin to 41°C did not
modulate itch intensity. Fruhstorfer and colleagues (1)
used a slightly different approach in that the thermode
was placed directly on the itching skin site. Skin tempe-
rature was then slowly increased from baseline at a rate
of 0.5°C/s until heat pain was reported. They observed
large inter-individual differences in the effect of warmth.
The majority of participants (n = 23) reported a decrease
in itch intensity as temperature increased. Notably this
effect was not restricted to the noxious range, but also
evident at sub-noxious temperatures below 40°C. A smal-
ler subset of participants (n = 7) reported the opposite pat-
tern, with itch increasing as temperature increased. A final
subset (n = 4) showed no influence of warmth on itch.
In summary, findings about a potential effect of in-
nocuous warmth on itch are mixed. The evidence sug-
gests that directly warming the affected skin site (1), as
opposed to an adjacent skin site (2, 4), may be a more
sensitive approach. Another limitation of existing stu-
dies is that inter-individual differences in baseline skin
temperatures and individual warm thresholds have so far
not been taken into account (6).
Regarding the effects of cooling on acute itch, findings
are, at first glance, contradictory. Yosipovitch et al. (4)
observed that repeatedly cooling skin adjacent to the
itch site to 15°C (i.e., at the threshold from innocuous to
noxious cold) does not influence itch intensity. Fruhstor-
fer and colleagues (1) observed that slowly cooling the
skin, from baseline at a rate 0.5°C/s until cold pain was
perceived, led to a decrease in itch intensity. This effect
was consistent across subjects and began to manifest
itself already in the innocuous temperature range below
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