Sensory perception and neuroanatomical structures in normal and grafted skin of burn survivors

Abstract

Background: This study compared the neural structures found in grafted skin of burn survivors with neural structures found in site-matched normal skin and correlated these structures with psychophysical measures of sensation. Methods: Fifteen skin-grafted male burn survivors (47.7 ± 10.4 years old) with deep partial- or full-thickness thermal burn injuries covering an average of 11 ± 5.6% of their total body surface and with normal skin at a matching, unburned, contralateral site were recruited into this study. Threshold determinations and magnitude estimations for touch, cold, warmth and heat-pain were performed at sites with grafted and normal skin, using Semmes-Weinstein monofilaments and the Medoc TSA 2001 thermal stimulator. Skin biopsies from both the grafted and normal sites were stained with antibodies for protein gene product 9.5 (PGP) and neurofilament 200 kDa. Nerve fibers in the epidermis and nerve fibers or bundles of nerve fibers in the superficial and deep dermis as well as innervated blood vessels, hair follicles and sweat glands were counted. Results: On average, the data were collected 43.1 ± 10.4 months after grafting. When thresholds on grafted skin were compared to thresholds on normal skin, they showed elevated sensory thresholds [touch ( p < 0.003), cold ( p < 0.031), warmth ( p < 0.009)]. Magnitude estimates of touch, cold and warmth differed on the two sides with sensations elicited from grafts being smaller than those from normal skin. Heat-pain thresholds and heat-pain magnitude estimations were not statistically different on the two sites. By comparison to the normal side, and consistent with the attenuated sensory functions of the grafts, counts of neural structures showed a reduction in innervation density; PGP-immunoreactive nerve fibers/bundles were reduced in grafted epidermis ( p < 0.026) and superficial dermis ( p < 0.001). The numbers of sweat glands ( p < 0.006) and hair follicles ( p < 0.001) were also reduced. The number of innervated blood vessels did not differ significantly on the two sides. There were significant correlations between sensory thresholds and the neuroanatomical variables: thresholds of cold and touch were correlated with the number of sweat glands in both grafted and normal skin ( r 2 = 0.56 and 0.50, respectively; p < 0.001), while warmth thresholds were significantly correlated with the number of innervated blood vessels in grafted skin ( r 2 = 0.62, p < 0.001). Encapsulated mechanoreceptors were not encountered in this study of hairy skin. Conclusions: Touch, cold and warmth thresholds and magnitude estimations do not return to normal levels after skin grafting in burn survivors. The elevation of thresholds and reduction of sensory intensity is accompanied by a general decrease in the density of nerve terminals. The lack, or numerical reduction, of sweat glands and innervated blood vessels was also indicative of diminished sensation on grafted skin.