Abstract
Atopic dermatitis (AD) is an often severely itching, chronic, inflammatory skin
disorder and may worsen due to stress and anxiety. Tachykinins have been suggested to
influence the level of inflammation as well as being involved in pruritus, stress and
anxiety.
The aim of the study was to investigate the role of tachykinins, including substance P
and neurokinin (NK) A, in the pathogenesis of AD, pruritus and worsening during
stress.
Initially an animal model was used to investigate innervation, substance P and the
neurokinin (NK)-1 receptor (R) in relation to eczema and stress using an
immunohistochemistry method. Chronic mild stress seemed to decrease innervation in
eczematous skin lesions and we recorded a decrease in substance P positive fibres in
stressed eczematous skin compared to in stressed control. In addition, a tendency of
increased levels of NK-1R m-RNA in skin of stressed compared to non-stressed
eczematous mice was apparent using PCR. A decrease of substance P
immunoreactivity was detected in the medial hippocampus of the brain in stressed
compared to in non-stressed eczematous mice.
Tachykinin expression was then examined in the skin of AD patients, and possible
correlations to clinical and psychodemographic parameters were investigated. The
numbers of substance P- and NKA positive nerve fibres and also of NKA positive
dermal cells were increased in lesional compared to non-lesional skin. In addition, there
was a correlation between the NK1-R positive cells, and the level of acanthosis and
inflammation, in the lesional skin. There was also a correlation between the depression
score and the number of the NK-1R positive cells in lesional as well as in non-lesional
skin.
Finally, the effect of an NK-1R antagonist, aprepitant, was evaluated in adult patients
with moderate-severe AD, compared to a standard topical treatment in an open
randomized trial. In both the treatment group and the control group significant
improvement was evident both regarding extent of disease and pruritus. However, there
was not any significant additional improvement for any of these parameters in the
aprepitant-treated patients compared to controls.
In conclusion, tachykinins seem to have a role in the pathogenesis and stressworsening of AD. However, this role seems to be complex and further investigations
are needed to fully understand these connections.
