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Pain is a major public health problem. The management of orofacial pain may be a difficult challenge to the medical and dental professions. Ideally, severe cases of this type of pain should be treated by a team drawn from several disciplines such as neurology, otolaryngology, dentistry and psychiatry. Trigeminal neuralgia patients develop brief, very severe unilateral pain, usually radiating from the upper or lower jaw toward the ear, and confined to the distribution of the trigeminal nerve. The pain may be triggered by chewing, shaving or exposure to cold wind. Most patients respond to carbamazepine, with phenytoin or baclofen as an alternative. Intractable pain may require surgical treatment. Horton's syndrome (cluster headache) is always unilateral and is often associated with unilateral lacrimation and rhinorrhoea. The pain is extreme, and its typical localisation the eye, forehead, temple, jaws, or teeth. Treatment with ergotamine and sumatriptan has been used with some success, calcium blockers (e.g., verapamil) being used as prophylaxis. Atypical facial pain is a continuous ache with intermittent episodes, localised to non-muscular, non-joint facial areas. The pain may be unilateral or bilateral, and may persist for many years. Typically, these patients consult a variety of specialists, such as dentists and otolaryngologists. Surgical procedures such as tooth extraction or sinus surgery, even if skillfully executed, exacerbate the condition, are are thus contraindicated. If the patient does not respond to reassurance, antidepressants may be tried. In sinusitis, the pain location is dependent upon which paranasal sinus is affected. Routine diagnostic nasal endoscopy and coronal plane computed tomography enable subtle pathological changes that are related to chronic pain to be identified. If medical treatment fails to afford relief, surgery should be considered. Pain, limited range of jaw motion, and joint noises are the common characteristics of temporomandibular disorders. Treatment usually consists of non-surgical means such as splints, occlusal equilibration, and non-steroidal anti-inflammatory drugs. Surgical treatment is indicated in a few carefully selected cases. Most dental pain is attributable to caries or periodontal disease. When pus is present, drainage affords excellent pain relief. Acute pericoronitis involving mandibular third molars responds to irrigation, removal of maxillary third molar trauma, and--in cases of serious infection--antimicrobial therapy. Early recognition of a case of chronic pain improves the chances of successful management, and avoids frustration and disillusion both to patient and doctor.

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The distribution of T- and B-lymphocytes, HLA-DR-expressing cells, and macrophages was determined using monoclonal antibodies in frozen biopsy sections of nasal polyps from 12 patients, and of nasal mucosa from five disease-free controls. The relative proportion and spatial distribution of different lymphoid cells was similar with regards to both nasal polyps and normal mucosa. Numerous scattered T lymphocytes (Leu4-positive) and HLA-DR-expressing macrophage/dendritic-like cells were shown and tended to accumulate in the subepithelial areas. Aggregates of T lymphocytes and HLA-DR-positive cells were also found close to deeper glands. In the submucosal clusters, the Leu3a-positive ("helper/inducer") cells were more common than the Leu2a-positive ("suppressor/cytotoxic") cells. Furthermore, a number of epithelial, non-lymphoid cells were found to express the HLA-DR antigen, which suggests an active role for the epithelium in the immunological response of the normal mucosa as well as that of the nasal polyp.

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The anatomy of the murine olfactory receptor was analyzed using high-resolution scanning electron microscopy with the aldehyde-osmium-dimethyl sulfoxide-osmium method. A good three-dimensional image of the receptor cell architecture was obtained. Within the olfactory vesicle, a complex tubular network was found that seemed to be physically associated with adjacent organelles, the basal aspect of cilia, and the lateral plasmalemma. It is assumed that these structures may be of significance during the olfactory transduction process.

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The effect of various doses of ipratropium bromide aerosol on nasal hypersecretion induced by five concentrations methacholine was studied in 24 patients with vasomotor rhinitis and excessive watery nasal secretion. The volume of nasal secretion was greater with each of the five increasing doses of methacholine from 7.5 to 120 mg/ml. The median volume of nasal secretion was alike in all patients after administration of methacholine only and after treatment by placebo followed by methacholine. When the patients were treated with ipratropium bromide prior to administering methacholine the volume of secretion was reduced significantly. With doses of 40 micrograms and 100 micrograms of ipratropium to each nostril a similar reduction in the volume of secretion occurred but a still greater reduction by the application of 200 micrograms of ipratropium when compared with treatment by the placebo. While the volume of secretion increased with each increasing concentration of methacholine, a similar pattern of reduced secretion for each concentration of methacholine was seen with each greater concentration of ipratropium. In patients with vasomotor rhinitis, treatment with ipratropium bromide was found to reduce significantly the hypersecretion induced by methacholine when compared with treatment by the placebo. This reduction was greater with greater doses of ipratropium.

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Replica preparations of dental pulp revealed membrane specializations indicating both exocytosis and endocytosis in the apical part of the odontoblast cell body and the proximal part of the odontoblast process. In tangential fractures, the plasmalemma exhibited protruding spheroids, considered to be the final stage in exocytosis. Other stages observed were plasmalemmal elevations covering underlying vesicles and surrounded by particle-free zones and fusion between vesicles and the cell membrane. Features indicative of endocytosis were plasmalemma studded patchwise with small circular craters 60-70 nm in diameter, often in association with intramembranous particles, and clusters of particles, probably constituting the sites of initiation of endocytotic vesicles in the plasmalemma.

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Electron micrographs of freeze-fracture replicas from the human olfactory mucosa were analysed regarding the structure of the axons of the olfactory receptor cells. In the lamina propria, numerous axons were generally invested with one Schwann cell. The ensheathed axons were often found in close contact with one another. Membrane specializations were not found at these sites, nor were tightening membrane junctions observed in the mesaxons. The Schwann cell plasmalemma exhibited caveolae, whose neck was surrounded by uniformly sized intramembranous particles evenly distributed over the axolemmal fracture planes. There was a marked difference in particle density between the P face (about 850/micron 2) and the E face (about 180/micron 2).

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The fine structure of the normal mucous membrane in the human maxillary sinus was investigated by means of the freeze-fracture technique. Special interest was directed to membrane structures in the epithelial cells. The morphology of tight junctions could be analysed. According to morphological criteria these junctions might be classified as "very tight". So called ciliary necklaces were well distinguishable. Their morphology seemed to be in concordance with the structure reported in other mammalian respiratory epithelia. Abluminally the epithelial cells frequently displayed abundant caveolae or micropinocytotic vesicles. The present investigation was performed as a preface to later studies on pathologically altered antral mucosa.

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Freeze-fracture replicas from the subodontoblast region gave a good three-dimensional comprehension of the structure of non-myelinated nerve fibres. Each Schwann cell ensheathed 1-15 axons with a mean diameter of 0.4 micron (0.1-1.2 micron). Many axons were not entirely ensheathed but were exposed to the extracellular space to various degrees. Tightening membrane specializations were not found in the mesaxons. The Schwann-cell plasmalemma exhibited caveolae with necks surrounded by evenly-sized intramembranous particles, typical of endocytosis. The nuclear envelope of Schwann cells showed a few typical pores and perinuclear cisterna. In tangential fractures, the axolemma displayed intramembranous particles evenly distributed over the axolemmal fracture planes. There was a marked difference in particle density between the P (600-650/micron2) and E (150-200/micron2) faces.

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The nuclear envelope was studied in several planes on freeze-fracture replicas. The inner and outer nuclear membranes were similar. Each presented two fracture faces, one with a higher intra-membranous particle density than the other. The perinuclear cisterna was bounded by outer and inner nuclear membranes about 40 nm apart. The nuclear pores of 85 nm diameter were evenly distributed over the nuclei. The pore density (5/micron2) was low compared with that in many other cells, but was of the same magnitude as is reported for the rat odontoblast.

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The outer surface of the myelin sheath was well visualized in electron micrographs of replicas and the distribution of its cytoplasm-containing portions could be analysed. Numerous caveolae, probably representing the surface stomata of endo- or exocytotic vesicles were found on the plasmalemmal surface overlying organelle-rich cytoplasmic regions. Membrane specializations of the tight-junction type were found at the outer and inner mesaxons of the myelin sheath as well as at the Ranvier node and Schmidt-Lanterman incisures. Presuming that so-called leakiness is related to the junctional morphology, these junctions would be classified as moderately leaky. The morphological features of the Schwann-cell nuclear envelope were essentially as described for other mammalian cells.

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The membrane morphology of cells in the pulp-dentin border zone in human teeth was scrutinized by means of the freeze-fracture technique. The tissue was fractured and replicated after mild demineralization in Na-EDTA. This procedure did not seem to influence the preservation of the tissue significantly. The odontoblastic cell bodies and their long processes lying within the predentinal and dentinal tubules were exposed. The technique made it possible to analyze the structural features of the apical part of the odontoblastic layer, including the 'terminal bar' region. This area exhibited large, irregularly shaped gap junctions. In some regions clusters of many small membranous pits or caveolae apparently representing pinocytotic vesicles were seen. The odontoblastic process displayed membrane protuberances projecting outward and abutting the inner tubular wall. In the predentinal and the adjacent dentinal regions, fine-caliber fibers (approximately 0.1-0.4 micron in diameter), presumably nerves, appeared in intimate relationship with the odontoblastic cell processes. At these sites the cell membrane displayed aggregations of membrane-associated particles, presumably gap junctions.

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The relationship between odontoblasts and adjacent cell structures within the odontoblastic cell layer was analyzed by means of the freeze-fracturing technique. Two principal forms of interodontoblastic cell structures were found. The first was tubular or thread-like in appearance, having a general diameter around 0.1-1.0 micron. From morphological criteria these were believed to represent small, unmyelinated nerve fibers. The second type of cell structure found between odontoblasts was more irregular and heterogeneous in outline, and often lamellar or branched. These slender formations sometimes proved to constitute cellular projections from adjacent odontoblasts or neighboring, subodontoblastic fibroblasts. Both the nerve-like fibers and the irregular branched cells between the odontoblasts showed morphological contact areas with odontoblastic cell bodies. At these sites the intracellular distances were reduced, and characteristic gap junctional complexes occurred. Nerve ending specialization or membrane structures indicating the presence of chemical synapses on the odontoblastic cell surface were not observed.

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The microvasculature of the subodontoblastic region in the human dental pulp was studied, using freeze-fracturing. This technique allows an analysis of the fine structure of the vascular endothelium with special reference to the membrane structure. The blood capillaries were noted to be of the non-fenestrated or continuous type, although a few fenestrated vessels were observed. The endothelial plasmalemma often exhibited bundles of fibrillar structures, presumably myofilaments. There was a relatively large number of micropinocytotic vesicles and the interendothelial spaces were closed juxtaluminally by tight junctions (zonulae occludentes). The junctions appeared mostly as two to four strands, seen as ridges or grooves on the cell membrane. Thin-walled, irregular, tissue channels lacking the typical, blood-vessel configuration were disclosed. These vessels were believed to represent lymphatics.

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