Novel itch reduction strategies focusing on pleasant touch brain pathways

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Itch is a global phenomenon reported by 20-27% of adults. Itch produces the desire to scratch, an innate behavioural response that is evolutionarily useful as it helps to remove insects and is therefore perceived as pleasurable. However, in pathological itch conditions the scratch response over time causes immense suffering and exacerbates the condition. In addition to increased suffering, chronic itch is also associated with other negative outcomes such as poor mental health, lack of sleep and lower reported mood. Currently, pharmaceutical itch treatments can result in negative side-effects such as topical corticosteroid withdrawal which can become more painful than the itch itself when used for a prolonged period. There is also the additional issue that a significant percentage of individuals are treatment resistant, leading their itch to persist. As a result, the need for non-pharmaceutical treatments needs to be developed. The skin contains several classes of nerve fibres that mediate dissociable aspects of somatosensation. Low threshold mechanoreceptors (LTMs) (myelinated A-beta and A-delta afferents) send rapid information to the spinal cord about innocuous touch. Unmyelinated, slow conducting C-fibre afferents convey emotional properties of pain and itch. C-tactile (CT) afferents encode for the pleasurable properties of touch. These somatosensory receptors have long been known to interact in a gated fashion. E.g. activation of LTMs can attenuate pain (gate control theory Melzack & Wall, 1965), and somatosensory evoked potentials evoked by electrical stimuli can be reduced by another somatosensory stimulus (Jones, 1981). CTs encode for a specific type of touch known pleasant touch which is a slow, gentle, caress-like stroke done within the velocity range of 1-10cm/s with optimal responses at 3cm/s. The pain-attenuating effects of affective touch have been demonstrated in both adults and infants. Recently published meta-analyses of brain responses to experimentally induced itch (Roberts et al., 2019) suggest that itch reliably activates overlapping, but dissociable brain regions to those produced by pleasant touch (e.g Morris, 2016). It has also been proposed that pleasant touch opens the gate to the primary somatosensory cortex (Shirato et al., 2018). Thus, CT mediated pleasant touch provides an avenue of exploration for non-pharmacological treatment of chronic skin conditions (Lloyd et al., 2015).Little is known about endogenous descending control of itch. However, recent functional Magnetic Resonance Imaging (fMRI) experiments suggest that distraction from itch with an executive function task does not reduce itch severity (Stumpf et al., 2017), whereas pain can induce central descending modulation of itch (Andersen et al., 2017). Taken together this suggests that increased load on the somatosensory system can modulate itch intensity. This has yet to be explored using pleasant touch.This PhD aims to characterise the psychological and neuropsychological responses to itch, and the interaction between itch and pleasant touch using neuroimaging techniques: - Demonstrate that the subjective experience of experimentally induced itch on the skin is modulated by stimulating CTs with pleasant touch.- Elucidate the brain architecture/pathways via which pleasant touch modulates itch-related brain activity to identify novel strategies to reduce itch.These objectives will be addressed using behavioural experiments as well as electrophysiological techniques such as electroencephalography. It is hypothesised that activation of CTs by pleasant touch will modulate the subjective experience of itch, in line with somatosensory gating and this will be observable in EEG band power, as well as modulating itch-related brain activity.We aim to advance our understanding of fundamental bioscience of itch and pleasant touch, to improve health across the lifetime for those with skin irritation, reducing the need for medical inter