The paradox of painless periodontal disease.

Periodontal diseases, primarily gingivitis and periodontitis, are characterised by progressive inflammation and tissue destruction. However, they are unusual in that they are not also accompanied by the pain commonly seen in other inflammatory conditions. This suggests that interactions between periodontal bacteria and host cells create a unique environment in which the pro-algesic effects of inflammatory mediators and factors released during tissue damage are directly or indirectly inhibited. In this review, we summarise the evidence that periodontal disease is characterised by an accumulation of classically pro-algesic factors from bacteria and host cells. We then discuss several mechanisms by which inflammatory sensitisation of nociceptive fibres could be prevented through inactivation or inhibition of these factors. Further studies are necessary to fully understand the molecular processes underlying the endogenous localised hypoalgesia in human periodontal disease. This knowledge might provide a rational basis to develop future therapeutic interventions, such as host modulation therapies, against a wide variety of other human pain conditions.

Hard and soft tissue considerations at mini-implant insertion sites.

Various factors influence where orthodontic mini-implants will be placed. This article highlights the pertinent variables that should find consideration when planning the placement of orthodontic mini-implants.

[Effects of pulpal inflammation on the activities of periodontal mechanoreceptive afferent fibers].

Response properties of periodontal single afferents were investigated in cats with inflammatory irritant-induced pulpitis. A deep dentin cavity was prepared on the right mandibular canine in order to apply an inflammatory agent and small fiber excitant, allyl-isothiocyanate (mustard oil: MO), and single afferents innervating the canine periodontal mechanoreceptor were dissected from the mandibular nerve bundle by examining impulse responses while applying mechanical stimuli to the tip of the crown. Evoked impulses by mechanical stimuli were increased in number for 15 minutes with MO application to the pulp when compared with those with mineral oil. The mechanoreceptive thresholds of single nerve fibers were decreased after the MO application to the pulp when compared with those with mineral oil. These results suggest that the alteration of responses in the periodontal afferent fiber, or the peripheral sensitization, can be produced by MO-induced pulpal inflammation probably due to the axon reflex mechanism in the furcating branches of nerve fibers innervating both the tooth pulp and periodontal ligament.

Pressor responses to isometric biting are evoked by somatosensory receptors in periodontal tissue in humans.

Jaw muscle contraction, such as mastication and biting (BT), is known to evoke pressor responses. We examined whether the responses were evoked by somatosensory receptors in periodontal tissue and, moreover, whether they were accompanied by altered arterial baroreflex sensitivity. In the first experiment, we measured mean arterial pressure, heart rate, and muscle sympathetic nerve activity from the peroneal nerve during 2-min isometric BT at 50% maximal voluntary contraction before [control (CNT)] and after pharmacological alveolar nerve block (BLK) in eight young men, while monitoring finger cutaneous vascular conductance, gingival vascular conductance (GVC), surface electromyogram of masseter muscle, and BT force. In the second experiment, cardiac and sympathetic baroreflex sensitivities were successfully determined in eight and five of the subjects, respectively, by the modified Oxford method during 5-min BT at 30% maximal voluntary contraction and also during resting without BT in CNT and BLK, respectively. In the first experiment, although BT in CNT and BLK significantly increased mean arterial pressure, heart rate, and total muscle sympathetic nerve activity (burst amplitude x burst incidence), and decreased finger cutaneous vascular conductance and GVC (P<0.05), all changes except GVC were markedly attenuated in BLK (P<0.05). There were no significant differences in integrated electromyogram and BT force among any trials. In the second experiment, although BT in CNT significantly decreased cardiac and sympathetic baroreflex sensitivities (both, P<0.05), these changes disappeared in BLK. These results suggest that somatosensory receptors in periodontal tissue were involved in pressor responses to isometric BT, which was accompanied by decreased arterial baroreflex sensitivity.

Regulation of bite force increase during splitting of food.

The purpose of the study was to analyze how increases in the bite force, during the splitting of food morsels of different hardness, are modulated, and to evaluate the role of periodontal mechanoreceptors in this control. Fifteen subjects were instructed to hold and split food morsels of different hardness (peanuts and biscuits) between a pair of opposing central incisors before and during anesthesia of the teeth. The split occurred at an average bite force of 9 N for biscuits and at an average bite force of 18 N for peanuts. The duration of the split phase was longer, and the split force rate higher, for peanuts compared with biscuits. Furthermore, a steeper force trajectory was observed for the peanut. During anesthesia of the teeth, the duration of the split phase increased and the mean split force rate decreased for peanuts. Force trajectories for peanuts and biscuits were indistinguishable during anesthesia. The present results show that when higher bite forces are needed to split a morsel, both the duration and the rate of the bite force produced is increased. Furthermore, adaptation of the bite force rate to the hardness of the food is dependent on information from periodontal mechanoreceptors.

The human periodontal membrane: focusing on the spatial interrelation between the epithelial layer of Malassez, fibers, and innervation.

OBJECTIVE: The purpose of the present study was to map the spatial interrelation of fibers, peripheral nerves, and epithelial layer of Malassez in human periodontal membrane in areas close to the root surfaces. MATERIAL AND METHODS: Four healthy permanent teeth extracted from four patients during puberty due to orthodontic treatment planning were analyzed. The extracted teeth, fixed in 4% neutral buffered formaldehyde for 5 days, were decalcified in 0.5 M EDTA. Paraffin blocks were sagittally cut in 5 microm thick serial sections and mounted on Superfrost Plus microscope slides. For survey, every fifth slide was stained with Alcian Blue/Van Gieson. Immunohistochemical reactions: Cytokeratin (wide spectrum screening) for epithelium, anti-vimentin for fibers, and anti-neuronal nuclei (NeuN) for innervation. RESULTS: The study indicates that the epithelial layer of Malassez is a border between different fiber morphologies and innervation patterns. Innervation is identified predominantly in the periodontal layer with tightly packed fibers close to the root surface. CONCLUSION: It is suggested that the genetic composition of the epithelial layer of Malassez in the periodontal membrane may be the key to understanding the different functions of the periodontal membrane and also the individual differences of these functions.

[Using dynamic magnetotherapy and transdermal electroneurostimulation in the combined treatment of patients with mandibular fractures and concomitant periodontal inflammatory diseases].

The objective of this study was to compare results of dynamic magnetotherapy (DMT), transdermal electroneurostimulation (TDENS), and traditional ultrahigh frequency (UHF) therapy in 473 patients with mandibular fractures and concomitant inflammatory diseases of paradontium. The parameters measured in the study included hygienic and paradontal indices, microcirculation patterns (using laser Doppler flowmetry), and the degree of mandibular fragment consolidation. It was shown that combined treatment with DMT and TDENS using an AMO-ATOS-E apparatus permits to eliminate clinical symptoms of paradontal inflammatory diseases twice as fast as traditional ultrahigh frequency therapy and ensures a two-fold reduction in the frequency of complications.

Periodontal-masseteric reflexes decrease with tooth pre-load.

The responses of incisal periodontal mechanoreceptors to increasing mechanical stimulation are known to follow a hyperbolic-saturating course. The implications of these properties for the reflexive control of bite-force have not been examined directly. In line with the above mentioned receptor characteristics, we hypothesized that the periodontal-masseteric reflex will reduce as a function of increasing incisal pre-load. In 10 participants, a central incisor was repeatedly tapped (0.4 N). We measured the modulation by pre-load (0.2-2.0 N) of the reflex frequency-response at and between 3 and 20 Hz. The entrainment of the reflex increased with frequency up to 20 Hz and diminished with increasing pre-load. Importantly, the hyperbolic relationship shown here between the periodontal-masseteric reflex and tooth pre-load agreed with the load/response relationships predicted by single-receptor and tooth movement studies. This study demonstrated that periodontal mechano-receptors are able to contribute to the ongoing control of only small bite-forces.

Alternative anesthetic technique for maxillary periodontal surgery.

BACKGROUND: Maxillary periodontal surgery typically requires multiple injections and may inadvertently affect facial structures such as the upper lip, lateral aspect of the nose, and lower eyelid. To minimize these sequelae and reduce the number of total injections, a relatively new injection technique has been proposed for maxillary procedures. The anterior middle superior alveolar (AMSA) injection is reported to effectively anesthetize maxillary teeth and associated gingival tissues extending from the buccal root of the first molar mesially to the central incisor with a single injection while avoiding undesirable side effects. The purpose of this article is to provide background information on the AMSA injection and demonstrate its use in a variety of maxillary periodontal surgeries. METHODS: Anesthesia was provided for five separate maxillary periodontal surgeries with unilateral or bilateral AMSA injections. Injections were administered via conventional syringe with a 27-gauge needle. Confirmation of anesthesia was subjectively tested with buccal mucosal sticks and palatal transgingival probing. RESULTS: The AMSA injection provided promising results for a variety of maxillary periodontal surgical procedures. Benefits of the AMSA injection included outstanding palatal hemostatic control, avoidance of undesirable collateral anesthesia, and a reduced number of cumulative injections. Drawbacks of the AMSA injection included occasionally inadequate buccal hemostatic control and short-lived anesthesia of the maxillary central incisors. CONCLUSION: The AMSA injection is a novel anesthetic technique that may prove useful for certain maxillary periodontal surgeries.

The role of periodontal mechanoreceptors in mastication.

The aim of this review is to discuss what is known about the reflex control of the human masticatory system by the periodontal mechanoreceptors and to put forward a method for standardised investigation. To deliver mechanical stimulus in a reproducible way, the following precautions are suggested: the stimulus should be brought into secure contact with the area of stimulation, and slack between the probe and the area to be stimulated should be taken up by the application of a preload. It is also important to ensure that there is minimal simultaneous activation of receptor systems other than the periodontal mechanoreceptors. It is also necessary to standardise the method for recording and analysing the response.

Systemic labeling and visualization of dental sensory nerves by the novel fluorescent marker AM1-43.

Systemic labeling of sensory nerves was performed by injecting a small amount of the styryl dye AM1-43 subcutaneously to the back skin of 4-week-old mice in order to determine its ability to stain sensory nerves. One or 3 days later, dental tissues were fixed and cryosectioned. Molars showed bright nerve fibers in the periodontal ligament and pulp. Nerve fibers in dentinal tubules approximately 100 microm from the pulp were also labeled. In the incisor, there were only few labelings in the pulp, although free nerve endings and Ruffini-type mechanosensors in the periodontal ligament on the lingual side were brightly labeled. The AM1-43-positive fibers were also labeled by anti-PGP9.5. AM1-43 is an excellent marker for sensory nerves and it may be useful for further investigations of dental innervation and in exploring new analgesics for tooth pain.

Physiological properties of molar-mechanosensitive periodontal neurons in the trigeminal ganglion of the rat.

Spike discharges from periodontal mechanosensitive neurones responding to the mechanical stimulation of molar teeth were recorded from the trigeminal ganglion of rats anaesthetized with pentobarbital sodium. Maxillary molar-sensitive units were close together in a narrow, lateral area of the maxillary division of the ganglion, whereas those of mandibular molar-sensitive units were scattered throughout the mandibular division. The majority of maxillary molar-sensitive units responded only to stimulation of the first molar. They were slowly adapting and responded most strongly to pressure applied to the lingual surface and buccal cusp of the tooth or to the buccal surface and lingual cusp. By contrast, approximately one-half of the mandibular molar-sensitive units were rapidly adapting, multitooth units that responded to tooth stimulation almost equally in all directions. The other half were slowly adapting and activated most effectively by pressure applied to the lingual surface and buccal cusp of the molar tooth. These slowly adapting units consisted of first molar-sensitive, single- and multitooth units. Differences in the response characteristics of the maxillary and mandibular molar-sensitive periodontal units may reflect differences in the sensory role of individual molars.

Encoding of tooth loads by human periodontal afferents and their role in jaw motor control.

Microneurography has been used to analyze the functional properties of human periodontal mechanoreceptors. Signals were recorded from single afferents in the inferior alveolar nerve while controlled forces were applied to the teeth. We have found that all periodontal afferents adapt slowly to maintained loads. Most afferents are tuned broadly to direction of force application, and about half respond to forces applied to teeth adjacent to the one to which the afferent distributes. Populations of periodontal afferents, nevertheless, reliably encode information about both the teeth stimulated and the direction of forces applied to the individual teeth. Information about the magnitude of steady forces is made available in the mean firing-rate response of periodontal afferents. Most afferents exhibit a marked "hyperbolic" relationship between the static discharge rate and the force amplitude; the highest sensitivity to changes in static force is observed at forces below 1 N. Similarly, the dynamic sensitivity is highest at low forces. These afferents efficiently encode food contact during biting and continuously discharge while food is held between the incisors. Subjects spontaneously exert low contact forces matched to the sensitivity characteristics of these periodontal afferents when holding food substances between the incisors. If periodontal afferent information is not available, the control of the hold forces is severely impaired. Moreover, since only a few afferents encode information about the rapid and strong force increase employed to bite through food, we conclude that subjects rely on signals from periodontal afferents to regulate the jaw muscles primarily when they first contact, manipulate and hold food substances between the teeth. A potential role for periodontal afferents in the spatio-intensive control of jaw actions is discussed.

[Functional characteristics of periodontium sensing apparatus and its significance in prosthetic stomatologic clinic].

Using developed by us method and instrument Periosensomer the sensor function of the periodontium on the initial stages of masticatory act (test of holding and splitting of food object) in persons with different functional periodontium status was explored. Evaluation of the sensor function of the periodontium and dynamics of the sensor reaction during holding and splitting of food object can be used as the method of functional diagnostics in the prosthetic stomatological clinic.

Neurologic Regulation and Orthodontic Tooth Movement.

Pain and discomfort are prevalent symptoms among the vast majority of patients with fixed orthodontic appliances and is the most disliked aspect of treatment. The periodontium is a highly innervated structure that also provides the necessary trophic factors, such as nerve growth factor, which promote neuronal survival, maintenance and axonal growth, via interaction with specific nerve surface receptors, such as TrkA. Various types of nerves are found in the periodontium, including thinly myelinated and unmyelinated sensory fibers that express the neuropeptides substance P and calcitonin gene-related peptide among others. Tooth movement activates peripheral sensory nerve endings, which transmit painful signals to the brain after being processed at the trigeminal spinal nucleus, resulting in local expression of pain related genes, such as c-Fos. Concurrently, an attendant inflammatory process is detected in the trigeminal spinal nucleus, including activation of astrocytes, microglia and neurons. This complex neurologic reaction to tooth movement mediates orthodontic pain and also serves a source of neurogenic inflammation exhibited in the trigeminal spinal nucleus and the periodontium. Activated periodontal sensory fibers release neuropeptides in the periodontal environment, which in turn induce a local inflammatory cascade aiding in alveolar bone turnover and tooth movement per se. Control of pain with nonsteroidal anti-inflammatory drugs and other prescription or over-the-counter pain killers effectively reduce this neurologic reaction and alleviate the attendant pain, but also reduce the neurogenic inflammatory component of orthodontic tooth movement causing a slowdown in bone turnover and consequently delaying orthodontic treatment.

Expression of neuropeptides and bone remodeling-related factors during periodontal tissue regeneration in denervated rats.

Increasing evidence indicates that bone remodeling is under the control of factors related to neuronal regulation, but the underlying mechanisms remain largely unknown. The aim of this study is attempted to assess the effect of denervation on neuropeptide expression and bone remodeling-related factors in the periodontal tissue regeneration process. rats underwent transection of the left inferior alveolar nerve (IAN-T) and surgery to produce bilateral periodontal defects; then, alveolar tissue was obtained from the animals of each group at 1, 2, 4, 6 and 8 weeks after the operation. The expression levels of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) were quantified by real-time PCR and Western blot techniques, and immunohistochemical staining was applied to investigate the in situ expression of OPG and RANKL. Osteoclasts were identified by tartrate-resistant acid phosphatase staining. The expression levels of calcitonin gene-related peptide (CGRP) mRNA and substance P (SP) mRNA were also quantified by real-time PCR. Mandibles with only periodontal defects were used as controls. After denervation, the OPG/RANKL ratio was reduced in the IAN-T groups due to decreased OPG mRNA and protein (P < 0.05) and a simultaneous increase in RANKL mRNA and protein expression (P < 0.05). On the other hand, the number of osteoclasts in periodontal defect areas increased, especially at 2 weeks, and at this time point, the expression of RANKL mRNA and protein peaked. The mRNA expression levels of neuropeptides CGRP and SP mRNA were monitored throughout the entire progress and exhibited a trend that was similar to that of the OPG/RANKL ratio, i.e., a downward trend over 1-2 weeks, an increase until 6 weeks, then back to the normal levels at 8 weeks. Innervation influences the OPG/RANKL ratio and neuropeptide expression, both of which govern the periodontal alveolar bone regeneration processes.

Morphology and synaptic connections of slowly adapting periodontal afferent terminals in the trigeminal subnuclei principalis and oralis of the cat.

Previous studies suggest that sensory information from primary afferent fibers is processed in a distinct manner in the individual subnuclei of trigeminal sensory nuclear complex. The present study has addressed this issue by using intra-axonal labeling with horseradish peroxidase to examine the ultrastructure and synaptic organization of axon terminals from slowly adapting (SA) periodontal afferents in the ventral subdivision (Vpv) of principalis and the rostro-dorsomedial part (Vo.r) of oralis. Our observations are based on complete or near-complete reconstructions of 139 synaptic boutons in Vpv and 105 in Vo.r. All the labeled boutons contained clear, spherical, synaptic vesicles and were presynaptic to unlabeled dendrites, and they were frequently postsynaptic to unlabeled axon terminals containing pleomorphic synaptic vesicles (P-endings). The P-endings frequently formed axodendritic synapses on dendrites which received axodendritic synapses from labeled boutons (synaptic triads). On the basis of the number of contacts, synaptic arrangements associated with the labeled boutons could be subgrouped into simple (one or two contacts), intermediate (three or four contacts), and complex (five or more contacts) types. The labeled boutons varied from round to elongated forms with smooth to more irregular or scalloped contours. The boutons with scalloped contour were much more frequent in the complex type. The boutons of the intermediate type were significantly smaller than the complex type and larger than the simple type. The SA periodontal afferent terminals participated in each type of synaptic arrangements in Vpv, but were mostly of the simple type in Vo.r. The size of labeled boutons was significantly larger in Vpv than in Vo.r. The total number of axodendritic and axoaxonic contacts per labeled bouton was significantly higher in Vpv than in Vo.r. Another difference was the more frequent occurrence of synaptic triads in Vpv than in Vo.r. These observations provide evidence that sensory information from primary afferent fibers is processed in a different manner in the two subnuclei.

Central terminations of low-threshold mechanoreceptive afferents in the trigeminal nuclei interpolaris and caudalis of the cat.

Previous studies indicate that vibrissa, nonvibrissa, guard hair, hairy skin, and periodontal ligament afferents give rise to morphologically distinct terminal arbors in the trigeminal nuclei principalis (Vp) and oralis (Vo) in the cat. The present study describes the extent to which morphological and functional relationships exist in the nuclei interpolaris (Vi) and caudalis (Vc). Twenty-two fibers were physiologically characterized and stained by intra-axonal HRP injection techniques. The fast adapting (FA) vibrissa (VF) afferents gave rise to compact and circumscribed arbors in Vi and Vc. These tended to be larger in Vc than in Vi. The slowly adapting (SA) vibrissa (VS) afferents in Vi and Vc had more widespread and larger arbors than those of the VF afferents. The VS arbors in Vc tended to be larger and less circular than those in Vi. Guard hair (GH) afferents gave rise to circumscribed arbors in both nuclei, but those in Vc tended to have larger and more circular arbors than those in Vi. Down hair (DH) afferents gave rise to small, circumscribed arbors or a few distinct patches of boutons within a small area in Vi; arbors in Vc were less extensive and "stringy." Unlike other afferents, DH arbors were larger in Vi than in Vc, but smaller than those of GH afferents in either nuclei. The SA hairy skin (SS) afferents had arbors that were widespread with a few distinct patches of boutons; the arbors in Vc were larger than those in Vi. The arbors of SS afferents were smaller than those of VS and GH afferents in both nuclei. Like GH afferents, FA periodontal ligament (PF) afferents gave rise to large and circumscribed arbors in Vi, although the arbors in Vc were smaller and less dense. The present study demonstrated significant functional and morphological relationships for primary afferents in Vi and Vc, thus suggesting that sensory information from each of the distinct fiber or functional classes is processed in a characteristic manner in the individual nuclei.

Distribution and central projections of primary afferent neurons that innervate the masseter muscle and mandibular periodontium: a double-label study.

A double-label strategy was used to determine the distribution and central projections of primary afferent neurons that innervate the periodontium and muscles of mastication in cats. Central injections of either Fast Blue (FB) or a mixture of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) and HRP were made into one of three cytoarchitectonically distinct regions of the spinal trigeminal nucleus. These regions included the subnucleus oralis (Vo), the subnucleus interpolaris (Vi), and the medullary dorsal horn (MDH). In each case, injections were also made into the periodontium of the ipsilateral mandibular teeth or into the ipsilateral masseter muscle. FB injections preceded the peroxidase injections by at least 48 hours and total survival time ranged from 72 to 96 hours. Animals were perfused with phosphate-buffered paraformaldehyde (4%; pH 7.2). Serial frozen sections were made through the brainstem and trigeminal ganglion. Tetramethylbenzidine was used as a chromagen to demonstrate HRP and sections were viewed with brightfield and epifluorescent illumination. Cells containing peripherally injected tracer were observed in the lateral portion of the ganglion and in the mesencephalic nucleus (Vmes). Double-labeled ganglion cells were observed in most cats that received periodontal injections in combination with central injections in the dorsal part of spinal trigeminal nucleus regardless of the rostrocaudal level of the central injection. In the animals that received intramuscular injections, double-labeled ganglion cells were observed only in the animals that received central injections caudal to the Vo. Double-labeled Vmes perikarya were observed in cats that received either intramuscular or periodontal injections in combination with central injections into the MDH and Vo but not in animals that received injections into the Vi. These results demonstrate that ganglion cell periodontal afferents project to the three major rostrocaudal subdivisions of the spinal trigeminal nucleus while ganglion cell muscle afferents have more limited central projections to caudal regions of the nucleus. Masseter and periodontal Vmes afferents also project ot the spinal trigeminal nucleus--specifically, to the Vo and MDH. These findings are consistent with physiological observations regarding the role of periodontal and masseteric afferents in oral and facial reflexes and somesthetic mechanisms.

Electron microscopic observation of synaptic connections of jaw-muscle spindle and periodontal afferent terminals in the trigeminal motor and supratrigeminal nuclei in the cat.

Previous studies indicate that the trigeminal motor nucleus (Vmo) and supratrigeminal nucleus (Vsup) receive direct projections from muscle spindle (MS) and periodontal ligament (PL) afferents. The aim of the present study is to examine the ultrastructural characteristics of the two kinds of afferent in both nuclei using the intracellular horseradish peroxidase (HRP) injection technique in the cat. Our observations are based on complete or near-complete reconstructions of 288 MS (six fibers) and 69 PL (eight fibers) afferent boutons in Vmo, and of 93 MS (four fibers) and 188 PL (four fibers) afferent boutons in Vsup. All the labeled boutons contained spherical synaptic vesicles and were presynaptic to neuronal elements, and some were postsynaptic to axon terminals containing pleomorphic, synaptic vesicles (P-endings). In Vmo neuropil, MS afferent boutons were distributed widely from soma to distal dendrites, but PL afferent boutons predominated on distal dendrites. Most MS afferent boutons (87%) formed synaptic specialization(s) with one postsynaptic target while some (13%) contacting two or three dendritic profiles; PL afferents had a higher number of boutons (43%) contacting two or more dendritic profiles. A small but significant number of MS afferent boutons (12%) received contacts from P-endings, but PL afferent boutons (36%) received three times as many contacts from P-endings as MS afferents. In Vsup neuropil, most MS (72%) and PL (87%) afferent boutons formed two contacts presynaptic to one dendrite and postsynaptic to one P-ending, and their participation in synaptic triads was much more frequent than in Vmo neuropil. The present study indicates that MS and PL afferent terminals have a distinct characteristic in synaptic arrangements in Vmo and Vsup and provides evidence that the synaptic organization of primary afferents differs between the neuropils containing motoneurons and their interneurons.