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The Pain in Neuropathy Study (PiNS): a cross-sectional observational study determining the somatosensory phenotype of painful and painless diabetic neuropathy.

Themistocleous AC, Ramirez JD, Shillo PR, Lees JG, Selvarajah D, Orengo C, Tesfaye S, Rice AS, Bennett DL - Pain (2016)

Bottom Line: The DN4 questionnaire demonstrated excellent sensitivity (88%) and specificity (93%) in screening for NeuP.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
Disabling 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.

No MeSH data available.


Related in: MedlinePlus

(A) Scatter plot and median (interquartile range [IQR]) of Toronto Clinical Scoring System (TCSS) scores for study participants with no peripheral diabetic neuropathy, and diabetic neuropathy with no neuropathic pain (NeuP), mild NeuP, moderate/severe NeuP. Kruskal–Wallis, Dunn multiple comparison test: **P < 0.01. (B) Scatter plot and median (IQR) of intraepidermal nerve fibre density (IENFD) from the distal leg for study participants with no peripheral diabetic neuropathy, and diabetic neuropathy with no NeuP, mild NeuP, moderate/severe NeuP. Intraepidermal nerve fibre densities were determined for 182 (87%) study participants. Kruskal–Wallis, Dunn multiple comparison test: **P < 0.01. (C) Heat maps obtained from the 7-day pain diary demonstrating the areas of NeuP (in red) and non-NeuP (in blue) within the study participants with diabetic neuropathy and no NeuP, mild NeuP, and moderate/severe NeuP.
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Figure 3: (A) Scatter plot and median (interquartile range [IQR]) of Toronto Clinical Scoring System (TCSS) scores for study participants with no peripheral diabetic neuropathy, and diabetic neuropathy with no neuropathic pain (NeuP), mild NeuP, moderate/severe NeuP. Kruskal–Wallis, Dunn multiple comparison test: **P < 0.01. (B) Scatter plot and median (IQR) of intraepidermal nerve fibre density (IENFD) from the distal leg for study participants with no peripheral diabetic neuropathy, and diabetic neuropathy with no NeuP, mild NeuP, moderate/severe NeuP. Intraepidermal nerve fibre densities were determined for 182 (87%) study participants. Kruskal–Wallis, Dunn multiple comparison test: **P < 0.01. (C) Heat maps obtained from the 7-day pain diary demonstrating the areas of NeuP (in red) and non-NeuP (in blue) within the study participants with diabetic neuropathy and no NeuP, mild NeuP, and moderate/severe NeuP.

Mentions: A similar proportion of study participants with mild NeuP and moderate/severe NeuP reported NeuP in their hands; however, those with moderate/severe NeuP experienced NeuP over a greater surface area of their hands (P < 0.05, Mann–Whitney U test) (Fig. 3C). There were no differences in either the frequency or surface area distribution of NeuP over the leg between study participants with mild NeuP and moderate/severe NeuP (Fig. 3C). Using the NPSI, study participants with moderate/severe NeuP reported greater severity of symptoms across all parameters of the NPSI compared with those with mild NeuP (Table 3).


The Pain in Neuropathy Study (PiNS): a cross-sectional observational study determining the somatosensory phenotype of painful and painless diabetic neuropathy.

Themistocleous AC, Ramirez JD, Shillo PR, Lees JG, Selvarajah D, Orengo C, Tesfaye S, Rice AS, Bennett DL - Pain (2016)

(A) Scatter plot and median (interquartile range [IQR]) of Toronto Clinical Scoring System (TCSS) scores for study participants with no peripheral diabetic neuropathy, and diabetic neuropathy with no neuropathic pain (NeuP), mild NeuP, moderate/severe NeuP. Kruskal–Wallis, Dunn multiple comparison test: **P < 0.01. (B) Scatter plot and median (IQR) of intraepidermal nerve fibre density (IENFD) from the distal leg for study participants with no peripheral diabetic neuropathy, and diabetic neuropathy with no NeuP, mild NeuP, moderate/severe NeuP. Intraepidermal nerve fibre densities were determined for 182 (87%) study participants. Kruskal–Wallis, Dunn multiple comparison test: **P < 0.01. (C) Heat maps obtained from the 7-day pain diary demonstrating the areas of NeuP (in red) and non-NeuP (in blue) within the study participants with diabetic neuropathy and no NeuP, mild NeuP, and moderate/severe NeuP.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 3: (A) Scatter plot and median (interquartile range [IQR]) of Toronto Clinical Scoring System (TCSS) scores for study participants with no peripheral diabetic neuropathy, and diabetic neuropathy with no neuropathic pain (NeuP), mild NeuP, moderate/severe NeuP. Kruskal–Wallis, Dunn multiple comparison test: **P < 0.01. (B) Scatter plot and median (IQR) of intraepidermal nerve fibre density (IENFD) from the distal leg for study participants with no peripheral diabetic neuropathy, and diabetic neuropathy with no NeuP, mild NeuP, moderate/severe NeuP. Intraepidermal nerve fibre densities were determined for 182 (87%) study participants. Kruskal–Wallis, Dunn multiple comparison test: **P < 0.01. (C) Heat maps obtained from the 7-day pain diary demonstrating the areas of NeuP (in red) and non-NeuP (in blue) within the study participants with diabetic neuropathy and no NeuP, mild NeuP, and moderate/severe NeuP.
Mentions: A similar proportion of study participants with mild NeuP and moderate/severe NeuP reported NeuP in their hands; however, those with moderate/severe NeuP experienced NeuP over a greater surface area of their hands (P < 0.05, Mann–Whitney U test) (Fig. 3C). There were no differences in either the frequency or surface area distribution of NeuP over the leg between study participants with mild NeuP and moderate/severe NeuP (Fig. 3C). Using the NPSI, study participants with moderate/severe NeuP reported greater severity of symptoms across all parameters of the NPSI compared with those with mild NeuP (Table 3).

Bottom Line: The DN4 questionnaire demonstrated excellent sensitivity (88%) and specificity (93%) in screening for NeuP.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
Disabling 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.

No MeSH data available.


Related in: MedlinePlus