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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 mean ± 95% CI of z-scores for thermal quantitative sensory testing (QST) parameters in study participants with no neuropathic pain (NeuP), mild NeuP, and moderate/severe NeuP. One-way analysis of variance (ANOVA), least significant difference (LSD) post hoc test: *P < 0.05; **P < 0.01. (B) Scatter plot and mean ± 95% confidence interval of z-scores for mechanical QST parameters in study participants with no NeuP, mild NeuP, and moderate/severe NeuP. One-way ANOVA, LSD post hoc test: **P < 0.01. (C) Loss and gain of sensory function. Comparison of study participants with no NeuP, mild NeuP, and moderate/severe NeuP who have QST values outside the 95% confidence interval of the German research network of neuropathic pain reference database. The y-axis shows the percentage of patients in each group with ‘gain’ of sensory function plotted upwards and “loss” of sensory function plotted downwards. Data analysed with χ2 test of association: †P < 0.05, ††P < 0.01 between no NeuP and moderate/severe NeuP, ##P < 0.01 between no NeuP and mild NeuP, ‡P < 0.05 between mild NeuP and moderate/severe NeuP. CDT, cold detection threshold; CPT, cold pain threshold; HPT, heat pain threshold; MDT, mechanical detection threshold; MPS, mechanical pain sensitivity; MPT, mechanical pain threshold; PPT, pressure pain threshold; TSL, thermal sensory limen; VDT, vibration detection threshold; WDT, warm detection threshold; WUR, wind-up ratio.
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Figure 5: (A) Scatter plot and mean ± 95% CI of z-scores for thermal quantitative sensory testing (QST) parameters in study participants with no neuropathic pain (NeuP), mild NeuP, and moderate/severe NeuP. One-way analysis of variance (ANOVA), least significant difference (LSD) post hoc test: *P < 0.05; **P < 0.01. (B) Scatter plot and mean ± 95% confidence interval of z-scores for mechanical QST parameters in study participants with no NeuP, mild NeuP, and moderate/severe NeuP. One-way ANOVA, LSD post hoc test: **P < 0.01. (C) Loss and gain of sensory function. Comparison of study participants with no NeuP, mild NeuP, and moderate/severe NeuP who have QST values outside the 95% confidence interval of the German research network of neuropathic pain reference database. The y-axis shows the percentage of patients in each group with ‘gain’ of sensory function plotted upwards and “loss” of sensory function plotted downwards. Data analysed with χ2 test of association: †P < 0.05, ††P < 0.01 between no NeuP and moderate/severe NeuP, ##P < 0.01 between no NeuP and mild NeuP, ‡P < 0.05 between mild NeuP and moderate/severe NeuP. CDT, cold detection threshold; CPT, cold pain threshold; HPT, heat pain threshold; MDT, mechanical detection threshold; MPS, mechanical pain sensitivity; MPT, mechanical pain threshold; PPT, pressure pain threshold; TSL, thermal sensory limen; VDT, vibration detection threshold; WDT, warm detection threshold; WUR, wind-up ratio.

Mentions: The data for thermal QST parameters for study participants with DPN are summarised in Figure 5A. The mean z-scores for all thermal parameters, apart from the cold detection threshold in participants with moderate/severe NeuP, fell within the normative range of the DFNS healthy control data, although data from individual participants did fall outside the normative range. Between-group comparisons revealed significant differences in the loss-of-function direction, and the shift towards thermal hypoaesthesia was greatest in the study participants with moderate/severe NeuP. The only thermal parameter that showed no differences across all 3 groups was cold pain thresholds as most study participants reached the cut-off temperature indicating a “flooring effect”. The mean z-scores for all thermal parameters for the study participants without DPN all fell within the normative range and were significantly higher across parameters when compared with study participants with DPN (Supplementary Figure 1, available online as Supplemental Digital Content at http://links.lww.com/PAIN/A226).


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 mean ± 95% CI of z-scores for thermal quantitative sensory testing (QST) parameters in study participants with no neuropathic pain (NeuP), mild NeuP, and moderate/severe NeuP. One-way analysis of variance (ANOVA), least significant difference (LSD) post hoc test: *P < 0.05; **P < 0.01. (B) Scatter plot and mean ± 95% confidence interval of z-scores for mechanical QST parameters in study participants with no NeuP, mild NeuP, and moderate/severe NeuP. One-way ANOVA, LSD post hoc test: **P < 0.01. (C) Loss and gain of sensory function. Comparison of study participants with no NeuP, mild NeuP, and moderate/severe NeuP who have QST values outside the 95% confidence interval of the German research network of neuropathic pain reference database. The y-axis shows the percentage of patients in each group with ‘gain’ of sensory function plotted upwards and “loss” of sensory function plotted downwards. Data analysed with χ2 test of association: †P < 0.05, ††P < 0.01 between no NeuP and moderate/severe NeuP, ##P < 0.01 between no NeuP and mild NeuP, ‡P < 0.05 between mild NeuP and moderate/severe NeuP. CDT, cold detection threshold; CPT, cold pain threshold; HPT, heat pain threshold; MDT, mechanical detection threshold; MPS, mechanical pain sensitivity; MPT, mechanical pain threshold; PPT, pressure pain threshold; TSL, thermal sensory limen; VDT, vibration detection threshold; WDT, warm detection threshold; WUR, wind-up ratio.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 5: (A) Scatter plot and mean ± 95% CI of z-scores for thermal quantitative sensory testing (QST) parameters in study participants with no neuropathic pain (NeuP), mild NeuP, and moderate/severe NeuP. One-way analysis of variance (ANOVA), least significant difference (LSD) post hoc test: *P < 0.05; **P < 0.01. (B) Scatter plot and mean ± 95% confidence interval of z-scores for mechanical QST parameters in study participants with no NeuP, mild NeuP, and moderate/severe NeuP. One-way ANOVA, LSD post hoc test: **P < 0.01. (C) Loss and gain of sensory function. Comparison of study participants with no NeuP, mild NeuP, and moderate/severe NeuP who have QST values outside the 95% confidence interval of the German research network of neuropathic pain reference database. The y-axis shows the percentage of patients in each group with ‘gain’ of sensory function plotted upwards and “loss” of sensory function plotted downwards. Data analysed with χ2 test of association: †P < 0.05, ††P < 0.01 between no NeuP and moderate/severe NeuP, ##P < 0.01 between no NeuP and mild NeuP, ‡P < 0.05 between mild NeuP and moderate/severe NeuP. CDT, cold detection threshold; CPT, cold pain threshold; HPT, heat pain threshold; MDT, mechanical detection threshold; MPS, mechanical pain sensitivity; MPT, mechanical pain threshold; PPT, pressure pain threshold; TSL, thermal sensory limen; VDT, vibration detection threshold; WDT, warm detection threshold; WUR, wind-up ratio.
Mentions: The data for thermal QST parameters for study participants with DPN are summarised in Figure 5A. The mean z-scores for all thermal parameters, apart from the cold detection threshold in participants with moderate/severe NeuP, fell within the normative range of the DFNS healthy control data, although data from individual participants did fall outside the normative range. Between-group comparisons revealed significant differences in the loss-of-function direction, and the shift towards thermal hypoaesthesia was greatest in the study participants with moderate/severe NeuP. The only thermal parameter that showed no differences across all 3 groups was cold pain thresholds as most study participants reached the cut-off temperature indicating a “flooring effect”. The mean z-scores for all thermal parameters for the study participants without DPN all fell within the normative range and were significantly higher across parameters when compared with study participants with DPN (Supplementary Figure 1, available online as Supplemental Digital Content at http://links.lww.com/PAIN/A226).

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