Ph.D. Defence by Hjalte Holm Andersen

PROGRAM 

See the Invitation here

ABSTRACT

Chronic itch, like chronic pain, is a common clinical problem that is associated with a markedly reduced quality of life for the affected patients. Itch is major symptom in several of the most prevalent dermatologic diseases (e.g., atopic eczema, psoriasis and urticaria) but it also occurs in a variety of non-cutaneous conditions (e.g., neuropathic and cholestatic itch). Chronic itch is often difficult to treat, has a detrimental impact on sleep quality as well as attention, and is consistently linked to increased rates of anxiety and depression.

Mechanistically, itch and pain are complexly entwined. While analgesic opioids facilitate itch, scratch-induced pain can abolish itch, thus suggesting an antagonistic relationship between the two sensations. At the same time, however, there is substantial overlap between pruritic and algogenic peripheral mediators as well as receptors, and strikingly similar patterns of neuronal sensitization for itch and pain have been documented. Recent evidence suggests that itch arise from at least two distinct peripheral cutaneous pruriceptive subpopulations, which are subsets of a larger population of neurons that also respond to various noxious stimuli (nociceptors). Thus much of the psychophysical research methodology developed in the pain field can be converted and used to increase our understanding itch – and in particular to explore the sensory neuronal features that are unique to itch.

Within this context, the aim of this PhD-project was to explore itch as a somatosensory modality using histaminergic and non-histaminergic models of itch and itch sensitization in humans for three purposes: 1) to assess itch topography and itch sensitization in healthy controls (first study), 2) to evaluate the antipruritic effect of capsaicin-induced epidermal nerve-ablation in a mechanistic proof-of-concept study (second study), 3) To explore potential pathway-specific itch and cutaneous pain sensitization in patients with chronic itch due to atopic dermatitis (third study).

Results from the first study suggested that von Frey filaments above the tactile detection range and below the pain threshold can be used to assess itch sensitization (hyperknesis) and that there is considerable heterogeneity in chemical and mechanically evoked itch sensitivity between spinal versus trigeminal innervated areas. Results from the second study demonstrated profound antipruritic and anti-hyperknetic effects of high-concentration capsaicin pretreatment and suggested that the two most commonly applied models of itch in humans rely on TRPV1-positive cutaneous fibers. Finally, the third study revealed pathway-specific non-histaminergic itch sensitization as well as mechano-nociceptive sensitization occurring both intra- and extra-lesionally in patients with atopic dermatitis.  

In conclusion, histaminergic and non-histaminergic models of itch and itch sensitization are useful tools in both human experimental and clinical itch research towards improved understanding of the mechanisms behind acute and chronic itch.