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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

Scatter plot of (A) Toronto Clinical Scoring System (TCSS), and (B) MRC sensory sum score scores, against the 7-day pain intensity diary mean showing a correlation of clinical neuropathy severity and neuropathic pain intensity (Spearman correlations).
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Figure 4: Scatter plot of (A) Toronto Clinical Scoring System (TCSS), and (B) MRC sensory sum score scores, against the 7-day pain intensity diary mean showing a correlation of clinical neuropathy severity and neuropathic pain intensity (Spearman correlations).

Mentions: The TCSS total score was significantly higher in study participants with NeuP compared with no NeuP (Fig. 3A and Supplementary Table, available online as Supplemental Digital Content at http://links.lww.com/PAIN/A226). The study participants with a NeuP reported more frequent sensory symptoms such as paraesthesiae and numbness, which was also of greater intensity. Patients with painful neuropathy also had a more severe DPN on clinical examination. There was greater proximal spread of clinical signs as evidenced by a higher Medical Research Council (MRC) sensory sum score (Supplementary Table 2, available online as Supplemental Digital Content at http://links.lww.com/PAIN/A226). The TCSS and MRC sensory sum scores correlated with NeuP intensity (Fig. 4). The nerve conduction studies (Supplementary Table 2, available online as Supplemental Digital Content at http://links.lww.com/PAIN/A226) and IENFD (Fig. 3 and Supplementary Table 2, available online as Supplemental Digital Content at http://links.lww.com/PAIN/A226) did not discriminate between study participants with and without a NeuP. Sural sensory nerve responses were absent in 54% of study participants with diabetic neuropathy; and in study participants with preserved responses, the amplitudes were reduced with slowing of conduction. Peroneal motor response was absent in 23% of study participants with diabetic neuropathy; and in study participants with preserved responses, the amplitudes were reduced with slowing. There were no electrophysiological differences between participants with and without NeuP (Supplementary Table 2, available online as Supplemental Digital Content at http://links.lww.com/PAIN/A226). The IENFD measured in a biopsy taken at 10 cm above the lateral malleolus was markedly reduced among all study participants with a peripheral neuropathy and did not correlate with the mean pain scores and was not significantly different between groups (Fig. 3 and Supplementary Table 2, 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)

Scatter plot of (A) Toronto Clinical Scoring System (TCSS), and (B) MRC sensory sum score scores, against the 7-day pain intensity diary mean showing a correlation of clinical neuropathy severity and neuropathic pain intensity (Spearman correlations).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4834814&req=5

Figure 4: Scatter plot of (A) Toronto Clinical Scoring System (TCSS), and (B) MRC sensory sum score scores, against the 7-day pain intensity diary mean showing a correlation of clinical neuropathy severity and neuropathic pain intensity (Spearman correlations).
Mentions: The TCSS total score was significantly higher in study participants with NeuP compared with no NeuP (Fig. 3A and Supplementary Table, available online as Supplemental Digital Content at http://links.lww.com/PAIN/A226). The study participants with a NeuP reported more frequent sensory symptoms such as paraesthesiae and numbness, which was also of greater intensity. Patients with painful neuropathy also had a more severe DPN on clinical examination. There was greater proximal spread of clinical signs as evidenced by a higher Medical Research Council (MRC) sensory sum score (Supplementary Table 2, available online as Supplemental Digital Content at http://links.lww.com/PAIN/A226). The TCSS and MRC sensory sum scores correlated with NeuP intensity (Fig. 4). The nerve conduction studies (Supplementary Table 2, available online as Supplemental Digital Content at http://links.lww.com/PAIN/A226) and IENFD (Fig. 3 and Supplementary Table 2, available online as Supplemental Digital Content at http://links.lww.com/PAIN/A226) did not discriminate between study participants with and without a NeuP. Sural sensory nerve responses were absent in 54% of study participants with diabetic neuropathy; and in study participants with preserved responses, the amplitudes were reduced with slowing of conduction. Peroneal motor response was absent in 23% of study participants with diabetic neuropathy; and in study participants with preserved responses, the amplitudes were reduced with slowing. There were no electrophysiological differences between participants with and without NeuP (Supplementary Table 2, available online as Supplemental Digital Content at http://links.lww.com/PAIN/A226). The IENFD measured in a biopsy taken at 10 cm above the lateral malleolus was markedly reduced among all study participants with a peripheral neuropathy and did not correlate with the mean pain scores and was not significantly different between groups (Fig. 3 and Supplementary Table 2, 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