Human digital Meissner's corpuscles are not doubly innervated

Recent studies have shown that murine and avian Meissner-like corpuscles are innervated by two distinct mechanoreceptor afferents with different functional properties. In addition, there is evidence that one subpopulation of Meissner corpuscles of monkeys is doubly innervated by mechanoreceptors and nociceptors. In humans, however, most Meissner corpuscles are supplied by a single axon. In the present study, different techniques were used (silver impregnation, immunohistochemistry for axon markers, axonal 3D reconstruction, and double immunofluorescence associated with confocal laser microscopy) to analyze whether human digital Meissner's corpuscles have double innervation. The percentage of Meissner corpuscles with apparent double innervation was minimal, about 2%, but these data were not confirmed when sections processed for double immunofluorescence for peripherin plus neurofilament proteins or TrkB plus Ret were analyzed. In fact, TrkB co-localized with Ret in the axon of Meissner's corpuscles. In the 3D axonal reconstructions, there was no evidence of double innervation but the single axon had different calibers along its path and very fine collateral protrusions. The present results demonstrate that most human digital Meissner's corpuscles (around 95-98%) are innervated by a single axon in which TrkB and Ret co-localize, instead of being supplied by two independent TrkB- and Ret-positive axons as occurs in other species.