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It currently remains unclear, why some patients with entrapment neuropathies develop neuropathic pain (neuP) whereas others have non-neuP, presumably of nociceptive character. Studying patients with carpal tunnel syndrome (CTS), this cross-sectional cohort study investigated changes in somatosensory structure and function as well as emotional wellbeing specific to the presence and severity of neuP.Patients with CTS (n=108) were subgrouped by the DN4 questionnaire into those without and with neuP. The latter group was further subdivided into mild and moderate/severe neuP using a pain visual analogue scale. N=32 participants served as healthy controls. All participants underwent a clinical examination, quantitative sensory testing (QST), electrodiagnostic testing (EDT) and skin biopsy to determine structural integrity of dermal and intraepidermal nerve fibres. Patients also completed questionnaires evaluating symptom severity and functional deficits, pain distribution, sleep quality and emotional wellbeing. The overall prevalence of neuP in patients with CTS was 80%, of which 63% had mild neuP. Symptom severity and functional deficits as well as somatosensory dysfunction were more pronounced with the presence and increasing severity of neuP. No difference was identified among patient groups for EDT and nerve fibre integrity on biopsies. The severity of neuP was accompanied by more pronounced deficits in emotional wellbeing and sleep quality. Intriguingly, extraterritorial spread of symptoms was more prevalent in patients with moderate/severe neuP, indicating the presence of central mechanisms. NeuP is common in patients with CTS and its severity is related to the extent of somatosensory dysfunction and a compromise of emotional wellbeing.

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