Are symptoms in pathologic scars related to nerve function or density? A scoping review

Background: Hypertrophic scars and keloids are forms of pathologic scarring that can give rise to pain and pruritus. The link between nerve function and nerve density and the symptoms in pathologic scars (PS) remains unclear. Objective: We aim to assess current knowledge on nerve function and nerve density in PS, and to explore a possible association between alterations in sensibility/nerve density and pathologic scar symptoms. Methods: A scoping review was conducted. After performing a systematic search using PubMed, Embase and Web-of-Science, relevant papers were selected and analyzed by 2 reviewers. Data was charted in tables in combination with a narrative summary of main findings. Results: Nineteen studies were included. Overall, functional sensibility in PS seems disturbed, with a higher frequency of allodynia and altered thermosensory thresholds, suggesting involvement of small fiber neuropathy. Nerve fiber density varied with the investigated skin layer and the used staining techniques, which implied limitations to compare findings from different studies. However, evidence suggests involvement of neuropeptides in the pathologic scar formation and symptomatology. Conclusions: Wide heterogeneity between studies exists. Therefore, no firm conclusions can be formulated. However, evidence suggests involvement of the cutaneous nervous system by neurogenic inflammation in the pathophysiology of pathologic scars and their symptoms.