Low density of sympathetic nerve fibers relative to substance P-positive nerve fibers in lesional skin of chronic pruritus and prurigo nodularis

Abstract Background In prurigo nodularis (PN), an increase in the density of dermal substance P-positive (SP+) sensory nerve fibers has been demonstrated. In addition, the density of sympathetic nerve fibers is unchanged. Objective We aimed to investigate the density and balance of sensory and sympathetic dermal nerves in pruritus on normally appearing skin in comparison to PN. Methods In a parallel investigation in lesional and non-lesional skin routine histological and immunofluorescence staining against SP and tyrosine hydroxylase (TH) were performed. Results We found an increased density of dermal SP+ nerve fibers in PN and also in pruritus relative to sympathetic nerve fibers in affected areas compared to the unaffected site. The density of SP+ and TH+ nerves did not correlate with clinical parameters such as itch quality, duration or intensity. Sparse lymphocytic infiltration as found in affected pruritus skin may be a source of nerve growth factor and explain the hyperinnervation. Conclusion Similar to the situation in PN, chronic pruritus lesions also demonstrate a preponderance of SP+ sensory nerve fibers relative to sympathetic nerve fibers, which probably acts as a causal pro-inflammatory signal in development of pruritus. These findings suggest new therapeutic approaches in patients with chronic pruritus.