Neuropeptide-containing nerves in painful hypertrophic human scar tissue

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Abstract
Specimens of hypertrophic scar tissue (n= 9). non-hypertrophic, flat scar tissue (n= 5) and control skin (n= 3) were obtained from eight adult females (aged 22–56) and three adult males (aged 22–59). The specimens were studied histologically and immunohistochemically for vasoactive intestinal polypeptide, neuropeptide Y, calcitonin gene-related peptide, substance P, somatostatin, [Met]enkephalin, [Leu]enkephalin, and the enzyme dopamine β-hydroxylase. The non-hypertrophic scar tissues were not dissimilar to the control tissue, but contained connective tissue in bundles with a greater number of collagen fibres. In the hypertrophic scar tissue of some patients, the dermis contained adipose tissue displaced upwards from the hypodermis. The connective tissue contained densely packed collagen fibres and fibroblasts; this region was devoid of hair follicles, sweat glands and blood vessels, although they were observed in the region of loosely packed connective tissue. The normal skin contained all the neuropeptides studied, except somatostatin-, and dopamine β-hydroxylase-immunoreactive nerves, which were seen as single fibres or in nerve bundles, and were associated with blood vessels in the dermis. Neuropeptide Y-immunoreactive nerves were found in the arrector pili muscle, and neuropeptide Y-, vasoactive intestinal polypeptide-, calcitonin gene-related peptide-, [Met]enkephalin- and dopamine β-hydroxylase-containing nerves were found within sweat glands. In patients with flat, non-hypertrophic scar tissue, neuropeptides and dopamine β- hydroxylase-containing nerves were absent. In patients with hypertrophic scars, the density of neuropeptide Y-, vasoactive intestinal polypeptide-, substance P-, calcitonin gene-related peptide- and dopamine β-hydroxylase-immunoreactive nerves was greater in the dermis when compared with controls. They were found at the base of the epidermis, around blood vessels, and in sweat and sebaceous glands. Only substance P-immunoreactive nerves penetrated the densely packed collagen and fibroblast matrix, whereas neuropeptide Y-, calcitonin gene-related peptide-, vasoactive intestinal polypeptide- and dopamine β-hydroxylase-containing nerves were found in the loosely packed connective tissue. [Met]enkephalin-, [Leu]enkephalin- and somatostatin-immunoreactive nerves were rarely seen in all three groups of patients. In conclusion, neuropeptide-containing nerves appear to be present in patients with painful, hypersensitive, hypertrophic scars, but absent in flat, insensitive, non-hypertrophic scars.