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Alloknesis and hyperknesis—mechanisms, assessment methodology, and clinical implications of itch sensitization

Andersen, Hjalte Holma,b,*; Akiyama, Tasukub; Nattkemper, Leigh Annb; van Laarhoven, Antoinettea,c,d,e; Elberling, Jesperf; Yosipovitch, Gilb; Arendt-Nielsen, Larsa

doi: 10.1097/j.pain.0000000000001220
Comprehensive Review
Global Year 2018

Itch and pain share numerous mechanistic similarities. Patients with chronic itch conditions (for instance atopic dermatitis or neuropathic itch) often experience symptoms such as mechanical alloknesis and hyperknesis. These dysesthesias are analogous to the pain-associated phenomena allodynia and hyperalgesia, which are often observed, for example, in neuropathic pain conditions. Mechanical itch dysesthesias represent abnormal sensory states (caused by neuroplastic changes), wherein considerable itch is evoked, for instance by light cutaneous stimuli such as from clothing (alloknesis), or where increased itch is perceived in response to normally itch-evoking stimuli (hyperknesis). These itch sensitization phenomena have been explored in experimental human studies, observed in chronic itch patients, and in animal models of itch. Limited attention has been paid to these sensory phenomena in clinical studies, and it is unknown how they respond to antipruritics. Psychophysical quantitative sensory testing can quantify the presence, severity, and spatial extent of itch dysesthesias in chronic itch patients, providing a proxy measurement of itch sensitization. This review outlines current assessment techniques, knowledge on the mechanisms of mechanical alloknesis and hyperknesis, and presents the diverse results derived from clinical studies exploring the presence of itch dysesthesias in chronic itch patients. A key role of quantitative sensory testing and neuronal sensitization in patients with chronic pain is accepted and used in clinical assessments. However, the precise mechanisms and potential clinical implications of itch sensitization in chronic itch patients remain to be evaluated.

aLaboratory of Experimental Cutaneous Pain Research, SMI, Faculty of Medicine, Aalborg University, Aalborg, Denmark

bDepartment of Dermatology, Itch Center, University of Miami School of Medicine, FL, United States

cHealth, Medical and Neuropsychology Unit, Faculty of Social and Behavioral Sciences, Leiden University, Leiden, the Netherlands

dLeiden Institute for Brain and Cognition (LIBC), Leiden University, Leiden, the Netherlands

eDepartment of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands

fDepartment of Dermato-Allergology, Copenhagen University Hospital, Gentofte, Copenhagen, Denmark

Corresponding author. Address: Faculty of Medicine, Aalborg University, Fredrik Bajers Vej 7A, A2-203, Aalborg E, 9220, Denmark. Tel.: +45 24 46 45 15; fax: +45 98 15 40 08. E-mail address: (H.H. Andersen).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Received December 20, 2017

Received in revised form March 06, 2018

Accepted March 13, 2018

© 2018 International Association for the Study of Pain
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