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.

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.

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.

Expression of calcitonin gene-related peptide in rat pulp and periodontal tissues by indirect immunofluorescence method.

The aim of this study was to investigate the expression of nerve fibers immunoreactive to calcitonin gene-related peptide (CGRP) in pulp and periodontal tissues of rats. Male Sprague-Dawley rats, aged 6 weeks, were sacrificed, and the jaws were excised, demineralized, and processed for indirect immunofluorescence staining. A considerably higher density of nerve fibers immunoreactive to CGRP was found in the dental pulp and gingiva than in periodontal ligament. The majority of pulpal CGRP immunopositive fibers that were located followed blood vessels parallel to the long axis of the root. A subodontoblastic network of fibers IR to CGRP was found in the coronal pulp in rat molars. In the periodontium, CGRP immunopositive fibers were mainly located in the periapical area and close to the alveolar bone. Gingiva was also well supplied with CGRP-IR nerves.

Tactile sensibility of single-tooth implants and natural teeth under local anesthesia of the natural antagonistic teeth.

INTRODUCTION AND AIM: The term osseoperception describes the capability of developing a subtle tactile sensibility over dental implants. The present clinical study aims at clarifying the question of how far tactile sensibility is to be attributed to the periodontium of the natural opposing tooth of the implant. MATERIAL AND METHOD: Thirty-two subjects with single-tooth implants with natural opposing teeth were included in this clinical, single-blind, split-mouth study. The natural antagonistic tooth of the implant and the corresponding natural contralateral tooth were anesthetized with a locally infiltrated articaine anesthetic. In a computer-assisted and randomized way, copper foils of varying thickness (0-100 µm) were placed interocclusally between the single-tooth implant and the natural opposing tooth, and between the contralateral pair of natural opposing teeth in order to investigate the active tactile sensibility according to the psychophysical method of constant stimuli and evaluate it statistically by the Weibull distribution. RESULTS: The average tactile sensibility of the implants with anesthetized antagonists at the 50% value calculated by means of the Weibull distribution was 20 ± 11 µm with a support area (90%-10% value) of 77 ± 89 µm. For the pair of natural teeth, the tactile sensibility at the 50% value was 16 ± 9 µm with a support area of 48.4 ± 93 µm. This resulted in an average intraindividual difference of 3.5 ± 7 µm at the 50% value and 29 ± 93 µm in the support area. The statistical calculations demonstrated an equivalent tactile sensibility (50% value) of the single-tooth implant and the contralateral natural control tooth with the natural antagonists being anesthetized in each case (double t-test, equivalence limit ± 8 µm, P < 0.01, power >80%). CONCLUSION: Apparently, the active tactile sensibility of single-tooth implants with natural opposing teeth is not only to be attributed to the periodontium of the opposing tooth but also to a perception over the implant itself. This could support the hypothesis according to which the implant may have a tactile sensibility of its own.

Detection of acid-sensing ion channel 3 (ASIC3) in periodontal Ruffini endings of mouse incisors.

The acid-sensing ion channel 3 (ASIC3), a member of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily, has been reported to participate in acid sensing, mechanosensation, and nociception. However, no information is available regarding the precise localization and function of this molecule in the periodontal ligament, which contains abundant sensory nerves originating from the trigeminal ganglion. The present study examined the expression of ASIC3 in the lingual periodontal ligament of mouse incisors by immunohistochemistry. Furthermore, the expression of ASIC3 in the trigeminal ganglion - which innervates the periodontal ligament - was investigated at protein (immunohistochemistry and quantitative analysis) and mRNA levels (RT-PCR technique and in situ hybridization histochemistry). Immunohistochemistry for ASIC3 was able to demonstrate dendritic profiles of the periodontal Ruffini endings in the mouse incisors. No thin fibers terminating as nociceptive free nerve endings exhibited ASIC3 immunoreactivity. Double immunofluorescent staining revealed ASIC3 immunoreaction in the axoplasm but not in the ordinary Schwann cells - including the associated terminal Schwann cells. Observation of the trigeminal ganglia showed variously sized neurons expressing ASIC3 immunoreaction; the most intense immunopositivity was found in the small and medium-sized neurons, as confirmed by in situ hybridization histochemistry using a specific cRNA probe. Quantitative analysis on trigeminal ganglion neurons showed that 38.0% of ASIC3 neurons could be categorized as medium-sized neurons which mediate mechanotransduction. These findings suggest that ASIC3 functions as a molecule for mechanosensation in the periodontal Ruffini endings.

The effect of experimental occlusal interferences on nerve growth factor levels in periodontal tissues.

OBJECTIVE: To test the hypothesis that experimental occlusal interferences increase the nerve growth factor (NGF) levels in periodontal tissues and cause an up-regulation of preprotachykinin-A (PPTA) mRNA. BACKGROUND: NGF is related to hyperalgesia and inflammation. PPTA mRNA, a primer of substance P, is a possible factor in the aetiology of pain. METHODS: Experimental interferences were created by placing inlays in the right maxillary molars of 15 dogs. The right side molars formed the experimental group. The left side molars served as controls. Three dogs with cavities prepared without changing the occlusion formed a sham group. The dogs in the first group were sacrificed, 3 at each time, after 3, 7, 14, 30, and 60 days. The sham group was sacrificed after 14 days. The levels of NGF in periodontal tissues and PPTA mRNA in the trigeminal ganglions were detected by ELISA and TR-PCR. Comparisons were made with paired t-tests and a multivariate MANOVA test. RESULTS: On all measurement days, there were higher levels of NGF mRNA, PPTA mRNA, and NGF on the experimental than on the control side in 14 of 15 comparisons and in the sham group. NGF production in periodontium was time-dependent. No differences in NGF protein levels were observed between the control and the sham groups. CONCLUSION: The results which need confirmation in further tests are of clinical interest. They indicate that occlusal experimental interferences may be an etiologic factor in oral facial pain by increasing mRNA and NGF protein levels in the periodontal tissues.

[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.

A comparison of the postnatal development of muscle-spindle and periodontal-ligament neurons in the mesencephalic trigeminal nucleus of the rat.

The trigeminal mesencephalic nucleus (Vmes) is known to include primary afferent neurons of jaw muscle spindles (MS neurons) and periodontal ligament receptors (PL neurons). The aim of this study was to clarify the postnatal development of Vmes neurons by comparing MS neurons with PL neurons using horseradish peroxidase labeling. We measured somal diameter and somal shape of MS and PL neurons in rats from postnatal day (P)7 to P70. No significant changes were seen between postnatal day P7 and P70 in somal diameter or somal shape of MS neurons. Conversely, PL neurons showed a larger somal diameter at P7 than at P14, and in terms of somal profile, multipolar neurons comprised 0% at P7, but 4.8% at P14 and 16.9% at P70. These findings suggest that PL neurons develop with the eruption of teeth, taking into account the fact that tooth eruption occurs from around P14 in rats. Conversely, the lack of postnatal changes in MS neurons is due to the fact that these neurons have been active since the embryonic period, as swallowing starts in utero.

Modulation of masseteric reflexes by simulated mastication.

It is well-known that limb muscle reflexes are modulated during human movements. However, little is known about the existence of equivalent masticatory muscle reflex modulation. We hypothesized that masticatory reflexes would be modulated during chewing so that smooth masticatory movements occur. To examine this hypothesis, we studied the modulation of inhibitory reflexes evoked by periodontal mechanoreceptor activation and of excitatory reflexes evoked by muscle spindle activation during simulated mastication. In 28 participants, 1- and 2-N mechanical taps were delivered to the incisor. Reflex responses to these taps were examined in the average masseteric electromyogram. To differentiate between periodontal mechanoreceptor- and muscle-spindle-mediated reflex components, we performed experiments prior to, and in the presence of, periodontal anesthesia. Both periodontal mechanoreceptor and muscle spindle reflexes were reduced during simulated masticatory movements.

[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.

GDNF expression in terminal schwann cells associated with the periodontal ruffini endings of the rat incisors during nerve regeneration.

The terminal Schwann cells (TSCs) which play crucial roles in regeneration of the periodontal Ruffini endings (RE) exhibit immunoreaction for glial cell line-derived neurotrophic factor (GDNF). However, no information is available regarding the role of GDNF in the periodontal RE during nerve regeneration. This study was undertaken to examine the changes in GDNF expression in the rat periodontal RE following transection of the inferior alveolar nerve (IAN) using immunohistochemistry for GDNF and S-100 protein, a marker for the TSCs. We additionally investigated the changes in expression of GDNF in the trigeminal ganglion (TG) at protein and mRNA levels. A transection to IAN induced a disappearance of the TSCs from the alveolus-related part (ARP), followed by a migration of spindle-shaped cells with S-100 but without GDNF immunoreactions into the tooth-related part (TRP) by postoperative (PO) week 2. At PO week 2, GDNF immunoreacted cellular elements increased in number in the ARP although the spindle-shaped cells without GDNF reaction remained in the TRP. After PO week 4, many GDNF-positive TSCs appeared in the ARP though the spindle-shaped cells vanished from the TRP. A real time RT-PCR analysis demonstrated the highest elevation of GDNF mRNA in the TG at PO week 2. These findings suggested the involvement of this molecule in the maturation and maintenance of the periodontal RE during regeneration. Taken together with our previous and current studies, it appears that the regeneration of the periodontal RE is controlled by multiple neurotrophins in a stage-specific manner.

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.

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.

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.

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.

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.

Branching patterns and intraosseous course of the mental nerve.

PURPOSE: The purpose of this study was to clarify the branching patterns of the mental nerve (MN) and intraosseous courses of the MN branches, and to determine the clinical relevance of the various courses of the MN branches. MATERIALS AND METHODS: We investigated the topography of the MN by dissecting 31 hemifaces of Korean cadavers. Based on the distribution area of the MN, it was divided into angular (A), medial inferior labial (ILm), lateral inferior labial (ILl), and mental (M) branches. We classified the branching patterns of the 4 branches of the MN into 5 types. RESULTS: Type II, in which the MN divided into 3 branches (A, ILm, and M), with the ILl branch separating from the A branch, was the most common (35.4%). The MN was classified based on the shape of the anterior loop into loop, straight, and vertical patterns, which constituted 61.5%, 23.1%, and 15.4%, respectively. In the mandibular canal, the inferior alveolar nerve completely divided into the MN and the dental nerve, which supplies the teeth. In 17 cases (81%), the nerve bundles constituting the A branch were located at the superior aspect, whereas the nerve bundles of the inferior labial and mental branches were in the middle and inferior aspects within the mandibular canal, respectively, at the mental foramen region. CONCLUSION: These observations can help clinicians to predict the location or extent of paresthesia in the facial region according to the location and extent of nerve damage during dental implant surgery or genioplasty.

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.