Substance P axons and sensory threshold increase in burn-graft human skin.

BACKGROUND: Our knowledge of afferent nerve fiber reinnervation of grafted skin following third-degree burn is limited by a lack of quantitative histological and psychophysical assessment from the same cutaneous area. The current study compares fiber profile and functional recovery measurements in injured and control skin from the same subject. MATERIALS AND METHODS: Nerve regeneration and modality-specific sensory thresholds were compared using immunocytochemical labeling with protein gene product 9.5 antibody to stain all axons and anti-substance P to label substance P axons (which are predominantly unmyelinated), as well as computerized instrumentation to obtain psychophysical estimates. RESULTS: Compared to control skin, threshold measures of pinprick (P < 0.001), warming (P < 0.001), touch (P < 0.001), and vibration (P < 0.01) were significantly elevated in burn-graft skin and correlated with histological analysis of skin biopsies obtained from the same site. Immunohistochemical staining of all axons innervating the dermis and epidermis revealed a significant reduction in burn-graft relative to control skin (54% decrease, P < 0.0001). In contrast, the incidence of substance P nerve fibers was significantly elevated in burn-graft (177% increase, P < 0.05) and appeared to correlate with patient reports of pruritus and pain. CONCLUSIONS: Observations support the hypothesis that sensory regeneration is fiber-size-dependent in burn-graft skin. The findings that substance P fiber growth increased while total fiber count decreased and that thermal threshold showed the greatest degree of functional recovery suggest that unmyelinated neurons have the greater ability to transverse scar tissue and reinnervate grafted skin following third-degree burn injury.

5-HT2 and 3 receptor antagonists suppress the response of rat type I slowly adapting mechanoreceptor: an in vitro study.

Previous experiments have shown an increase in rat type I mechanoreceptor responsiveness during arterial serotonin (5-hydroxytryptamine) infusion and the presence of serotonin immunostaining in Merkel cells. The current findings demonstrate that the 5-HT(2) antagonists ritanserin and ketanserin, as well as the 5-HT(3) antagonist MDL 72222, reduce type I response to a standardized mechanical stimulus in an in vitro skin preparation. In addition, ritanserin blocked the enhancement of type I response produced by 5-HT. These experiments suggest that serotonin is released during mechanical distortion of the Merkel cell membrane and alters action potential generation by the type I ending. In addition, it is possible that serotonin, released from outside the type I complex, influences mechanoreceptor responsiveness. For example, serotonin generated during inflammatory events could enhance type I response to mechanical stimulation and thereby increase symptoms of mechanical allodynia.