The Contribution of Peripheral Nerves to the Pleasure from Scratching an Itch: Evidence from a Neuronopathy Participant

Itch is 'an unpleasant sensation of the skin commonly triggering an urge to scratch'. In chronic itch, the persistent itch/scratch cycle is reinforced and sustained by the intense pleasure and reward gained from scratching - sometimes after the itch has been abolished, and despite negative consequences. Scratching an itch recruits multiple areas of the limbic system that control addictive behaviours such as craving and intense pleasure seeking. It is hypothesised here that the pleasure derived from scratching is significantly influenced by small-fibre afferent input, including Aδ and C-tactile afferents. Subjective and physiological responses to acute itch and scratching were obtained from control participants, and compared with responses from IW, a participant with a well characterised large-fibre sensory neuronopathy below C3. In the forearm, IW's responses to temperature change, and physiological responses to histamine iontophoresis (wheal and axon reflex flare) match control participants. IW perceived both histamine- and cowage-induced itch, although self-reported peak intensities were lower than for controls and required a greater dose to elicit a comparable itch percept. Rough, scratching touch was rated significantly more intensely on itchy skin by both control participants and IW, and improved touch localisation in IW. Scratching an itch on the forearm is pleasurable for IW, despite the lack of large, myelinated fibres, thereby supporting the hypothesis that mechanosensitive small-fibre afferents contribute to the pleasure of scratching an itch. KEY POINTS: Both histamine- and cowage-induced itch perception are preserved in a patient with large fibre neuronopathy. Gentle, dynamic touch (optimally activating C-tactile afferents) is significantly less pleasant on itchy skin, in control participants. As expected, scratching itchy skin is pleasant in control participants. The pleasure of scratching persists in a patient lacking large myelinated (Aβ) fibres, suggesting that small-fibre afferents, that is, Aδ and/or C-fibres such as C-tactile afferents, mediate some of this sensation. These findings provide insight into the peripheral neural mechanisms underlying itch relief, and may inform approaches to chronic itch management.