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Today, diagnosis and treatment of chest pain related to pathologic changes in the visceral pleura are often difficult. Data in the literature on the sensory innervation of the visceral pleura are sparse. The present study aimed at identifying sensory end-organs in the visceral pleura, and at obtaining more information about neurochemical coding. The immunocytochemcial data are mainly based on wholemounts of the visceral pleura of control and vagally denervated rats. It was shown that innervation of the rat visceral pleura is characterized by nerve bundles that enter in the hilus region and gradually split into slender bundles with a few nerve fibers. Separate nerve fibers regularly give rise to characteristic laminar terminals. Because of their unique association with the elastic fibers of the visceral pleura, we decided to refer to them as "visceral pleura receptors" (VPRs). Cryostat sections of rat lungs confirmed a predominant location on mediastinal and interlobar lung surfaces. VPRs can specifically be visualized by protein gene product 9.5 immunostaining, and were shown to express vesicular glutamate transporters, calbindin D28K, Na^sup +^/K^sup +^-ATPase, and P2X^sub 3^ ATP-receptors. The sensory nerve fibers giving rise to VPRs appeared to be myelinated and to have a spinal origin. Because several of the investigated proteins have been reported as markers for sensory terminals in other organs, the present study revealed that VPRs display the neurochemical characteristics of mechanosensory and/or nociceptive terminals. The development of a live staining method, using AM1-43, showed that VPRs can be visualized in living tissue, offering an interesting model for future physiologic studies.
Keywords: lung; P2X^sub 3^ ATP-receptors; vesicular glutamate transporters; visceral pleura; receptors
The visceral pleura is often considered to be insensitive to painful stimuli, and, as a consequence, is believed to lack a sensory innervation (1-3). In general medical literature, assumptions have been made about the innervation of the visceral pleura without referring to conclusive morphologic or physiologic data. Several authors indeed describe the visceral pleura as noninnervated (1-3), whereas others presume that nerves are present, but no sensory endings (4). Although early physiologic experiments (5) demonstrated that potential afferent fibers in the visceral pleura do not react to tactile, thermal, or pain stimuli, some more recent publications do suggest an autonomic innervation of the visceral pleura, containing afferent...