• Andreas C Themistocleous, Juan D Ramirez, Pallai R Shillo, Jonathan G Lees, Dinesh Selvarajah, Christine Orengo, Solomon Tesfaye, Andrew S C Rice, and David L H Bennett.
• aNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United KingdombDiabetes Research Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United KingdomcStructural & Molecular Biology, Division of Biosciences, University College London, London, United KingdomdPain Research Group, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital Campus, London, United KingdomePain Medicine, Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom.
• Pain. 2016 May 1; 157 (5): 1132-45.

AbstractDisabling neuropathic pain (NeuP) is a common sequel of diabetic peripheral neuropathy (DPN). We aimed to characterise the sensory phenotype of patients with and without NeuP, assess screening tools for NeuP, and relate DPN severity to NeuP. The Pain in Neuropathy Study (PiNS) is an observational cross-sectional multicentre study. A total of 191 patients with DPN underwent neurological examination, quantitative sensory testing, nerve conduction studies, and skin biopsy for intraepidermal nerve fibre density assessment. A set of questionnaires assessed the presence of pain, pain intensity, pain distribution, and the psychological and functional impact of pain. Patients were divided according to the presence of DPN, and thereafter according to the presence and severity of NeuP. The DN4 questionnaire demonstrated excellent sensitivity (88%) and specificity (93%) in screening for NeuP. There was a positive correlation between greater neuropathy severity (r = 0.39, P < 0.01), higher HbA1c (r = 0.21, P < 0.01), and the presence (and severity) of NeuP. Diabetic peripheral neuropathy sensory phenotype is characterised by hyposensitivity to applied stimuli that was more marked in the moderate/severe NeuP group than in the mild NeuP or no NeuP groups. Brush-evoked allodynia was present in only those with NeuP (15%); the paradoxical heat sensation did not discriminate between those with (40%) and without (41.3%) NeuP. The "irritable nociceptor" subgroup could only be applied to a minority of patients (6.3%) with NeuP. This study provides a firm basis to rationalise further phenotyping of painful DPN, for instance, stratification of patients with DPN for analgesic drug trials.

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