Alloknesis: a severe form of itch

Alloknesis refers to itch caused by stimuli that do not normally induce itch, particularly light mechanical stimuli, such as contact with clothes or other human bodies. This symptom occurs in patients who are affected by chronic itch. While alloknesis has been mainly described in patients with atopic dermatitis, it is probably present in numerous other conditions and can induce a severe burden. To date, it has mainly been diagnosed using von Frey filaments and validated questionnaires are lacking. Alloknesis differs from mechanical pruritus as it is linked to sensitization to pruritus and therefore occurs in pathological conditions, whereas mechanical pruritus (triggered by the presence of insects on the skin, for example) is a physiological phenomenon. While the role of central sensitization to pruritus in alloknesis is still poorly understood, the role of peripheral sensitization is becoming clearer. Interactions between low-threshold mechanoreceptors and spinal interneurons have a particularly important function. Both the mechanical labelled pathway and the polymodal pathway have been shown to contribute to mechanical alloknesis. The mechanical labelled pathway comprises dedicated primary sensory neurons, spinal interneurons and projection neurons that are functionally distinct from those involved in chemical itch. The polymodal pathway relies on a subset of primary sensory neurons traditionally associated with chemical itch, which can also transduce light mechanical stimuli through the activation of the mechanosensitive ion channel PIEZO1. Both converge onto the gastrin-releasing peptide (GRP)-GRP receptor chemical itch pathway in the spinal cord. Alloknesis is largely unknown to healthcare professionals and even less well known to patients, and is not actively investigated. Reducing the impact and occurrence of alloknesis should be a therapeutic goal. To date, it has not been investigated in clinical trials. A novel research domain is emerging concerning this symptom, which exerts a substantial impact on the daily lives of numerous patients.