ANATOMICAL SPECIALIZATIONS OF THE HUMAN PHARYNX

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DESCRIPTION (Applicant's abstract): What variables in the neuromuscular properties of the human pharynx make some patients more susceptible to aspiration, obstructive sleep apnea (OSA), acid reflux, cricopharyngeal spasm and other disorders of the pharyngeal region? In most mammals (and neonatal humans) the respiratory system is protected by overlapping the epiglottis and soft palate, however with separation of these structures the human at risk of aspiration, and this is often the cause of death in the elderly and neurologically impaired. At present the basic neuromuscular specializations of the human pharynx are poorly understood. In preliminary work numerous novel observations were made, one example is that of the human cricopharyngeus (CP) muscle; That the CP receives its innervation from multiple nerves, each of which supplies a distinct region within the muscle, and that it contains specialized muscle fibers. One of these, slow tonic muscle fibers (STMF) has a unique physiology. STMF are extremely rare in mammals but preliminary work has shown that they are widespread in human upper airway structures including the tongue and larynx. Moreover the particular distribution of these fiber suggests that they are directly related to distinct biomechanics. The proposed work will focus on clarifying the peripheral organization patterns of the human pharyngeal plexus and characterizing the intrinsic properties of the CP and the muscles surrounding the pharynx to answer the questions: what anatomic specializations are present that appear specific to humans and possibly speech and swallowing related? What variations in these specializations correlate with certain ethnic (black males OSA), genders (males reflux, OSA) and especially geriatric (CP spasm and aspiration) susceptibility to specific disorders? All studies will be done in human post-mortem tissue. The motor and sensory nerve supply to the pharyngeal region will be studied using Sihler's stain. An additional hypothesis to be tested is that the human glossopharyngeal nerve (IX) provides motor innervation not only to the traditionally described stylopharyngeus, but also to the CP and pharyngeal constrictor muscles as demonstrated by our preliminary studies. This will be studied by triple approaches: Sihler's stain whole-mount acetylcholinesterase (AChE) and silver stain, and Karnovsky-Roots' method. Another hypothesis to be tested is that most swallowing-related muscles are specialized and composed of neuromuscular compartments (NMC) as functional requirements. Our preliminary studies provided evidence for the existence of the NMC within the human CP inferior constrictor and geniohyoid muscles. In addition, the human CP appears to be a specialized skeletal muscle as it contains slow tonic and a-cardiac myosin heavy chain isoforms that are not normally present in limb muscles. The muscular specializations of the upper esophageal sphincter, pharyngeal constrictor and suprahyoid muscles will be explored using a wide variety of histochemical, immunohistochemical, electrophoretic and immunoblotting techniques The muscle fiber architecture, distribution of the fiber types and the major and unusual myosin heavy chain isoforms will be studied.