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A pain in the skin. Regenerating nerve sprouts are distinctly associated with ongoing burning pain in patients with diabetes
Author(s) -
Galosi E.,
La Cesa S.,
Di Stefano G.,
Karlsson P.,
Fasolino A.,
Leone C.,
Biasiotta A.,
Cruccu G.,
Truini A.
Publication year - 2018
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.1259
Subject(s) - diabetes mellitus , medicine , anesthesia , physical medicine and rehabilitation , endocrinology
Backgrounds Patients with diabetic polyneuropathy commonly suffer from ongoing burning pain and dynamic mechanical allodynia. In this clinical and skin biopsy study, we aimed at assessing how intraepidermal regenerating nerve sprouts are associated with these two types of pain. Methods We consecutively enrolled 85 patients with diabetic polyneuropathy. All patients underwent skin biopsy at the distal leg. Intraepidermal nerve fibres were immunostained with the anti‐protein gene product 9.5 ( PGP 9.5) to quantify all intraepidermal nerve fibres, and the growth‐associated protein 43 ( GAP 43) to quantify regenerating nerve sprouts. Results We found that the GAP 43‐stained intraepidermal nerve fibre density and the ratio GAP 43/ PGP 9.5 were significantly higher in patients with ongoing burning pain than in those without. The area of receiver operating characteristic (ROC) curve for the ratio GAP 43/ PGP 9.5 was 0.74 and yielded a sensitivity and specificity for identifying ongoing burning pain of 72% and 71%, respectively. Conversely, although the density of PGP 9.5 and GAP 43 intraepidermal nerve fibre was higher in patients with dynamic mechanical allodynia than in those without, this difference was statistically weak and the ROC curve analysis of skin biopsy variables for this type of pain failed to reach the statistical significance. Conclusion Our clinical and skin biopsy study showed that ongoing burning pain was strongly associated with regenerating sprouts, as assessed with GAP 43 immunostaining. This finding improves our understanding on the mechanisms underlying neuropathic pain in patients with diabetic polyneuropathy and suggests that the GAP 43/ PGP 9.5 ratio might be used as an objective marker for ongoing burning pain due to regenerating sprouts. Significance Our skin biopsy study showing that regenerating sprouts, as assessed with GAP43‐staining, were strongly associated with ongoing burning pain, improves our knowledge on the mechanisms underlying neuropathic pain in patients with diabetes