24 results on '"Byers, M."'
Search Results
2. Altered localization of Cav1.2 (L-type) calcium channels in nerve fibers, Schwann cells, odontoblasts, and fibroblasts of tooth pulp after tooth injury.
- Author
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Westenbroek RE, Anderson NL, and Byers MR
- Subjects
- Animals, Calcium Channels, L-Type ultrastructure, Dental Pulp cytology, Dental Pulp ultrastructure, Fibroblasts metabolism, Immunohistochemistry, Male, Microscopy, Electron, Nerve Fibers metabolism, Nerve Fibers ultrastructure, Odontoblasts metabolism, Rats, Rats, Sprague-Dawley, Schwann Cells metabolism, Time Factors, Calcium Channels, L-Type metabolism, Dental Pulp metabolism, Tooth Injuries metabolism
- Abstract
We have determined the localization of Cav1.2 (L-Type) Ca2+ channels in the cells and nerve fibers in molars of normal or injured rats. We observed high levels of immunostaining of L-type Ca2+ channels in odontoblast cell bodies and their processes, in fibroblast cell bodies and in Schwann cells. Many Cav1.2-containing unmyelinated and myelinated axons were also present in root nerves and proximal branches in coronal pulp, but were usually missing from nerve fibers in dentin. Labeling in the larger fibers was present along the axonal membrane, localized in axonal vesicles, and in nodal regions. After focal tooth injury, there is a marked loss of Cav1.2 channels in injured teeth. Immunostaining of Cav1.2 channels was lost selectively in nerve fibers and local cells of the tooth pulp within 10 min of the lesion, without loss of other Cav channel or pulpal labels. By 60 min, Cav1.2 channels in odontoblasts were detected again but at levels below controls, whereas fibroblasts were labeled well above control levels, similar to upregulation of Cav1.2 channels in astrocytes after injury. By 3 days after the injury, Cav1.2 channels were again detected in nerve fibers and immunostaining of fibroblasts and odontoblasts had returned to control levels. These findings provide new insight into the localization of Cav1.2 channels in dental pulp and sensory fibers, and demonstrate unexpected plasticity of channel distribution in response to nerve injury., (Copyright 2003 Wiley-Liss, Inc.)
- Published
- 2004
- Full Text
- View/download PDF
3. Patterns of fluoro-gold entry into rat molar enamel, dentin, and pulp.
- Author
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Byers MR and Lin KJ
- Subjects
- Aging, Analysis of Variance, Animals, Denervation, Dental Pulp Exposure metabolism, Dentin, Secondary metabolism, Male, Mandibular Nerve physiology, Odontoblasts physiology, Rats, Rats, Sprague-Dawley, Statistics, Nonparametric, Tooth Injuries metabolism, Dental Enamel Permeability, Dental Pulp metabolism, Dentin Permeability, Fluorescent Dyes pharmacokinetics, Stilbamidines
- Abstract
Permeabilities of enamel and dentin are not fully understood despite their importance for caries, restorative materials, and pulp-dentin-enamel interactions. We have found that Fluoro-Gold is useful for examining tooth permeability, and we designed studies to test the effects of aging, injury, neural function, and dentinal repair on its influx into vital rat teeth. We used fluorescence microscopy and immunocytochemistry to show that Fluoro-Gold rapidly penetrates enamel, the dentin-enamel junction, and outer dentinal acellular tubules, and then concentrates in odontoblasts, where it remains for weeks. As predicted, influx was greatest in immature teeth, and formation of reparative dentin impeded it. We expected that denervation would disrupt influx, because of neural regulation of dentinal fluid movement, but it did not. Damage to odontoblasts under injured dentin caused increased influx and efflux of Fluoro-Gold. Analysis of our data suggests that permeabilities of enamel and dentin to Fluoro-Gold are age-related, inter-dependent, and regulated by odontoblasts.
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- 2003
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4. The exact expression of glial fibrillary acidic protein (GFAP) in trigeminal ganglion and dental pulp.
- Author
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Ajima H, Kawano Y, Takagi R, Aita M, Gomi H, Byers MR, and Maeda T
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- Animals, Cerebellum metabolism, Dental Pulp ultrastructure, Glial Fibrillary Acidic Protein ultrastructure, Male, Mice, Mice, Knockout, Rats, Rats, Wistar, Trigeminal Ganglion ultrastructure, Cerebellum ultrastructure, Dental Pulp metabolism, Glial Fibrillary Acidic Protein metabolism, Trigeminal Ganglion metabolism
- Abstract
The expression in various cell types of peripheral tissues of glial fibrillary acidic protein (GFAP), first discovered as an intermediate filament specific for astrocytes, remains controversial owing to numerous reports of a wide distribution for GFAP-immunoreactivity in various cells. The present study employed immunohistochemistry to investigate the precise expression of GFAP in the dental pulp and trigeminal ganglion of adult rats and wild-type mice as well as GFAP-knockout mice. The exhibition of GFAP-immunoreactivity in the trigeminal ganglion was further examined by a reverse transcription polymerase chain reaction (RT-PCR) technique, and in situ hybridization histochemistry using a specific cRNA probe prepared by us. The immunoreaction for GFAP was recognizable in the axons, Schwann cells, and the fibroblasts in the dental pulp of rats and wild-type littermate mice. However, mice with null mutations in the GFAP gene remained immunoreactive for GFAP in all these locations. Intense GFAP-immunoreactivity was found in a small number of satellite cells in the trigeminal ganglion in all animals examined in this study. RT-PCR analysis demonstrated bands for the GFAP gene corresponding to the length expected from the primer design in the samples of trigeminal ganglion and dental pulp. In situ hybridization histochemistry also showed intense signals for GFAP mRNA in some satellite cells of the trigeminal ganglion, but never in the neurons. These data suggest that the GFAP-immunoreactive molecules in the pulpal axons and fibroblasts react non-specifically with the polyclonal antibody and are probably a closely related type of intermediate filament.
- Published
- 2001
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5. Neurotrophin receptors and nerve growth factor are differentially expressed in adjacent nonneuronal cells of normal and injured tooth pulp.
- Author
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Woodnutt DA, Wager-Miller J, O'Neill PC, Bothwell M, and Byers MR
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- Animals, Cell Communication, Chemotaxis, Leukocyte, Dental Pulp injuries, Male, Molar, Nerve Tissue Proteins metabolism, Neurons metabolism, Neutrophils immunology, RNA, Messenger metabolism, Rats, Rats, Sprague-Dawley, Receptor, Nerve Growth Factor genetics, Receptor, trkA genetics, Dental Pulp metabolism, Fibroblasts metabolism, Gene Expression Regulation, Odontoblasts metabolism, Receptor, Nerve Growth Factor biosynthesis, Receptor, trkA biosynthesis, Wound Healing
- Abstract
High-affinity tyrosine kinase A (trkA) neurotrophin receptors on neurons and nonneuronal cells elicit differentiation or survival functions in response to nerve growth factor (NGF), whereas the low-affinity neurotrophin (p75) receptor modulates trkA activity or can independently cause apoptosis or NFkappaB-mediated survival functions. We examined dental tissues for the presence of trkA-like immunoreactivity (trkA-IR), to determine which nonneuronal cell types express it in normal compared with inflamed teeth and how the trkA-positive cells relate to those expressing the p75 receptor and/or NGF. Normal and injured rat molars (dentin cavity for 4 h, 16-24 h, 3 days, 16 days, or 5 weeks) were immunoreacted using the ABC detection system for two anti-trkA antibodies (sTA, Santa Cruz Biotechnology; rTA, L. Reichardt) and antibodies against p75 and NGF, all of which also stained pulpal nerve fibers. We report that, when using the sTA antibody (recognizing the intracellular carboxy terminal), nonneuronal trkA-IR was found in odontoblasts of normal teeth and also in invading polymorphonuclear leukocytes (PMNs) and reparative odontoblasts after injury. When using rTA (recognizing the extracellular domain of the receptor), nonneuronal trkA-IR was only found in odontoblasts. Odontoblasts also had NGF-IR but did not label for NGF mRNA. The lack of odontoblast NGF mRNA suggests that NGF is passed from fibroblasts to the adjacent odontoblasts, where it is picked up by receptor-mediated mechanisms for regulation of odontoblast function. Tooth injury disrupts this system such that trkA-IR decreases in injured odontoblasts, p75 decreases in fibroblasts, and NGF is upregulated by fibroblasts and accumulates in the injured pulp and surviving odontoblasts. Pulpal NGF may contribute to chemoattraction for the invading leukocytes or their sTA-IR may have been induced in response to pulpal NGF. Thus, tooth pulp has a different distribution of nonneuronal NGF and its paracrine receptors during inflammation compared with normal conditions.
- Published
- 2000
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6. Normal development of dental innervation and nerve/tissue interactions in the colony-stimulating factor-1 deficient osteopetrotic mouse.
- Author
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Nagahama SI, Cunningham ML, Lee MY, and Byers MR
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- Acid Phosphatase analysis, Animals, Antigens, Differentiation analysis, Cell Division, Isoenzymes analysis, Macrophages, Mice, Mice, Mutant Strains, Nerve Endings chemistry, Nerve Tissue chemistry, Nerve Tissue cytology, Neurons, Afferent cytology, Osteoclasts, Tartrate-Resistant Acid Phosphatase, Thiolester Hydrolases analysis, Tooth Eruption, Tooth Root innervation, Ubiquitin Thiolesterase, Dental Pulp innervation, Macrophage Colony-Stimulating Factor physiology, Osteopetrosis physiopathology, Periodontium innervation, Tooth innervation
- Abstract
Dental innervation occurs concurrently with tooth development, eruption, and root formation and is suggested to interact with developing tissues. The purpose of the present study was to investigate dental innervation in osteopetrotic (op/op) mice, which carry a mutation of colony-stimulating factor-1 (CSF-1) and demonstrate sparse macrophages and osteoclasts, failure of bone resorption, lack of tooth eruption, and poor root formation. Jaw tissues from 21 mice in different age groups (7 days, 18 days, 26 days, 5 weeks, and 3 months) were prepared for immunocytochemistry and light microscopy. Immunocytochemistry with the neuronal marker protein gene product 9.5 (PGP 9.5), macrophage marker F4/80, double-labeling with F4/80 and PGP 9.5, and histochemical analysis using tartarate-resistant acid phosphatase (TRAPase) were carried out in selected sections. Molar and incisor development were arrested in the op/op mouse, and both types of teeth had bony occlusion of the eruptive pathway and failure of root formation. Third molar development in the normal mouse is delayed until after birth; therefore, it encounters different bone barriers and jaw structures than are present when first and second molars and incisors begin to develop after the second embryonic week. All three molars, however, completed crown formation prior to eruption failure. Partial root formation was seen in several homozygous op/op mice, and, in those cases, there was partial development of the periodontal ligament. Innervation of dental tissues that successfully formed was essentially normal in the mutant mice despite phenotypic deficiencies in macrophages and osteoclasts. The periodontal ligament was innervated with PGP 9.5-immunoreactive Ruffini mechanoreceptive endings in those cases in which the ligament formed, and op/op mice had remarkably normal sensory innervation of molar and incisor pulp despite failure of bone resorption, failure of root development, and arrested eruption. This study shows that op/op mice develop normal innervation in dental tissues and that dental nerve development proceeds independently of bone abnormalities and root failure in this animal.
- Published
- 1998
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7. Different localizations of growth-associated protein (GAP-43) in mechanoreceptors and free nerve endings of adult rat periodontal ligament, dental pulp and skin.
- Author
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Maeda T and Byers MR
- Subjects
- Animals, GAP-43 Protein, Immunohistochemistry, Microscopy, Immunoelectron, Neuronal Plasticity physiology, Rats, Rats, Sprague-Dawley, Receptors, Nerve Growth Factor metabolism, Dental Pulp metabolism, Dental Pulp ultrastructure, Mechanoreceptors metabolism, Mechanoreceptors ultrastructure, Membrane Glycoproteins metabolism, Nerve Endings metabolism, Nerve Endings ultrastructure, Nerve Tissue Proteins metabolism, Periodontal Ligament metabolism, Periodontal Ligament ultrastructure, Skin metabolism, Skin ultrastructure
- Abstract
Distributions of growth-associated protein-43 (GAP-43) in the periodontal ligament and dental pulp of adult rats were studied by light and electron microscopy. The mature periodontal ligament and dental pulp contained numerous GAP-43-positive neural elements, comprising periodontal Ruffini endings and thin nerve fibers, but expression patterns differed among the kinds of nerves. In the periodontal ligament of rat molars, immunoelectron microscopy revealed that GAP-43 like immunoreactivity in the Ruffini ending, an essential mechanoreceptor, was confined to the Schwann sheaths around the axon terminals and was not in the axon terminals themselves, unlike free endings that revealed axonal GAP-43. However, the lamellar Schwann cells associated with the cutaneous receptors did not exhibit any GAP-43 like immunoreactivity though they were intensely reactive for low affinity nerve growth factor receptor (p75-NGFR), a marker for lamellar Schwann cells in mechanoreceptors. The characteristically uniform expression of GAP-43 in the Schwann lamellae that surround the Ruffini mechanoreceptors of rat molar ligament suggests that Schwann cells are involved in the GAP-43 mediated plasticity of these receptors. On the other hand, the pulpal nerves were filled with the reaction products in their axonal spaces, suggesting the potential for neuronal plasticity during normal function and after tooth injury.
- Published
- 1996
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8. GFAP immunoreactivity in trigeminal ganglion satellite cells after tooth injury in rats.
- Author
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Stephenson JL and Byers MR
- Subjects
- Animals, Female, Immunohistochemistry, Rats, Rats, Sprague-Dawley, Dental Pulp injuries, Dental Pulp innervation, Glial Fibrillary Acidic Protein analysis, Neurons metabolism, Trigeminal Ganglion cytology, Trigeminal Ganglion metabolism
- Abstract
Glial fibrillary acidic protein (GFAP) is a member of a heterogeneous group of intermediate filaments in glial cells of both the central and peripheral nervous systems. We demonstrate here that satellite cells in the trigeminal ganglion (TG) increase immunoreactivity (IR) for GFAP in response to dental injury. The satellite cell reaction was most often confined to the somatotopic region of the ganglion that corresponded to the zone of damage in the periphery, although in some cases it was seen to spread out from a focal center in the maxillary region to neighboring zones corresponding to cell bodies that innervate other tissues such as the cornea. We used two methods to demonstrate that the increase in satellite cell GFAP-IR was site specific and injury related. First, by altering the site of the pulp exposure from the maxillary molars to the mandibular molars, we could change the site of satellite cell reaction in the TG. Second, we used combined retrograde transport of DiI from the molar pulp and GFAP immunofluorescence to show direct correspondence between neurons that innervate the molars and neurons that are encircled by GFAP-IR satellite cells. The satellite cell GFAP-IR was seen at 3 and 7 days, the longest time point examined here. This GFAP response in satellite cells around injured sensory neurons will be a useful tool in future studies of mechanisms in trigeminal pain and neuron-support cell interactions. We conclude that a GFAP-IR satellite cell reaction is induced in TG by an injury to the molar pulp in a site specific manner at 3-7 days.
- Published
- 1995
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9. Effect of electrical tooth stimulation on blood flow, interstitial fluid pressure and substance P and CGRP-immunoreactive nerve fibers in the low compliant cat dental pulp.
- Author
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Heyeraas KJ, Kim S, Raab WH, Byers MR, and Liu M
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- Animals, Blood Flow Velocity, Blood Pressure physiology, Calcitonin Gene-Related Peptide metabolism, Cats, Dental Pulp innervation, Dental Pulp physiology, Electric Stimulation, Extracellular Space physiology, Female, Immunohistochemistry, Male, Nerve Fibers metabolism, Pressure, Substance P metabolism, Vasodilation physiology, Dental Pulp blood supply
- Abstract
The effect of vasodilation on simultaneously measured interstitial fluid pressure (IFP, micropuncture) and blood flow (laser-Doppler) in the low compliant pulpal connective tissue was investigated in 10 cats. Vasodilation was induced by electrical stimulation of the tooth after pretreatment with the sympathetic blocker guanethidine. Visualization of the sensory neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP) was performed using immunocytochemistry. The study was designed to answer the following questions. (1) Does vasodilation promptly increase IFP in low compliant tissues? (2) Does an increase in IFP counteract the blood flow increase? (3) Does repeated electrical stimulation cause reduced staining of CGRP- and SP-immunoreactive nerve fibers in the dental pulp? Electrical stimulation resulted consistently in a nearly synchronous increase in both blood flow and IFP. IFP was nearly doubled, from 6.3 +/- 0.18 mm Hg in control to 11.7 +/- 0.44 mm Hg, whereas blood flow increased by 28%. However, despite continued vasodilation the IFP fell to control level, or even lower, within 1-5 min. The results indicate that the increased IFP will promote fluid absorption into the blood, counteracting a further IFP increase in low compliant tissues during vasodilation. Accordingly, transmural pressure is only transitorily reduced and compression of vessels does not take place. There was considerably less CGRP- and SP-immunoreactive fibers in the stimulated teeth than in the contralateral controls, suggesting that the vasodilation was caused by liberation of these sensory neuropeptides.
- Published
- 1994
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10. Dynamic plasticity of dental sensory nerve structure and cytochemistry.
- Author
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Byers MR
- Subjects
- Animals, Dentin chemistry, Dentin injuries, Dentin Sensitivity etiology, Humans, Nerve Fibers physiology, Nerve Tissue Proteins analysis, Nerve Tissue Proteins physiology, Neuronal Plasticity physiology, Neurons, Afferent chemistry, Neurons, Afferent physiology, Pulpitis complications, Tooth Injuries complications, Tooth Injuries physiopathology, Trigeminal Nuclei physiopathology, Dental Pulp innervation, Dentin innervation, Dentin Sensitivity physiopathology
- Abstract
Hypersensitive dentine responds to normal changes in touch or temperature with abnormal pain sensations. This paper reviews studies that have shown dynamic changes in sensory nerve structure, cytochemistry and location after tooth injury, suggesting that those changes contribute to dentine hypersensitivity. Nerve fibres containing calcitonin gene-related peptide (CGRP) are the main type of sensory fibre to innervate dentine. Evidence that many of those dentinal nerve endings originate from small myelinated fibres is presented here. The location of CGRP nerve terminals correlates with the pulpal gradients of nerve growth factor that have been demonstrated in normal teeth by in situ hybridization histochemistry. When shallow cavities are drilled into the outer dentine of rat molars a five-to-eight-fold increase in pulpal nerve growth factor precedes the extensive structural changes in the sensory nerve reactions eventually subside if healing occurs, but both continue if inflammation continues. Evidence correlating pulpal inflammation with long-term changes in central trigeminal pain pathways is reviewed. There can be extensive neuroplasticity after tooth injury, both within dental pain fibres and in central pain pathways. The timing of those alterations of nerve structure, location, and cytochemistry is consistent with their involvement in mechanisms of dentine hypersensitivity.
- Published
- 1994
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11. The injury response of pulpal NPY-IR sympathetic fibers differs from that of sensory afferent fibers.
- Author
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Oswald RJ and Byers MR
- Subjects
- Adrenergic Fibers drug effects, Animals, Calcitonin Gene-Related Peptide immunology, Calcitonin Gene-Related Peptide physiology, Histocytochemistry, Male, Nerve Growth Factors pharmacology, Neurons, Afferent drug effects, Neuropeptide Y immunology, Nociceptors physiology, Rats, Rats, Sprague-Dawley, Staining and Labeling, Substance P immunology, Substance P physiology, Adrenergic Fibers physiology, Dental Pulp injuries, Dental Pulp innervation, Neurons, Afferent physiology, Neuropeptide Y physiology
- Abstract
Light microscopic immunocytochemistry demonstrated that neuropeptide Y (NPY) containing sympathetic fibers in rat molars did not change morphology or staining characteristics after pulp exposure injury. This result, in combination with recent findings concerning NGF synthesis in injured pulp and NGF-receptor localization on pulpal sensory fibers, suggests that small diameter sensory fibers in pulp may be under NGF control, but NPY containing sympathetic efferent fibers are not. Thus, sympathetic fibers in tooth pulp have a different response to NGF compared to those in many other tissues.
- Published
- 1993
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12. Nerve fibers immunoreactive to protein gene product 9.5, calcitonin gene-related peptide, substance P, and neuropeptide Y in the dental pulp, periodontal ligament, and gingiva in cats.
- Author
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Heyeraas KJ, Kvinnsland I, Byers MR, and Jacobsen EB
- Subjects
- Animals, Biomarkers, Calcitonin Gene-Related Peptide analysis, Calcitonin Gene-Related Peptide metabolism, Cats, Dental Pulp blood supply, Epithelium innervation, Female, Gingiva blood supply, Gingiva innervation, Immunohistochemistry, Male, Microcirculation, Nerve Fibers immunology, Nerve Fibers physiology, Neurons, Afferent immunology, Neurons, Afferent physiology, Neuropeptide Y analysis, Neuropeptide Y metabolism, Neuropeptides metabolism, Periodontal Ligament blood supply, Receptors, Neuropeptide metabolism, Substance P analysis, Substance P metabolism, Thiolester Hydrolases metabolism, Ubiquitin Thiolesterase, Dental Pulp innervation, Neuropeptides analysis, Periodontal Ligament innervation, Thiolester Hydrolases analysis
- Abstract
The distribution patterns of nerve fibers immunoreactive (IR) to calcitonin gene-related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY) in the dental pulp, periodontal ligament (PDL), and gingiva were studied and compared with the complete innervation visualized by antibody to protein gene product (PGP) 9.5 in adult cats. The pulp showed considerably denser nerve supply for PGP 9.5, CGRP, and SP than the periodontal tissues. Most of the pulpal fibers were CGRP-IR, and approximately three to four times more IR fibers were labeled with CGRP than SP. Most fibers in the odontoblast area penetrating into the dentin tubules were CGRP-IR. NPY-IR nerves were mainly observed in connection with the larger blood vessels in pulp and PDL. In the PDL most nerves were localized in the apical third in connection with blood vessels, but CGRP-IR fibers extending close to root cementum were often observed. Immunoreactivity to PGP 9.5 and CGRP was frequently found in cell-like structures in connection with Malassez epithelium in the PDL and in some round epithelial-like cells located in the base of gingival rete pegs.
- Published
- 1993
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13. Effect of sensory denervation on the response of rat molar pulp to exposure injury.
- Author
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Byers MR and Taylor PE
- Subjects
- Animals, Calcitonin Gene-Related Peptide, Denervation, Dental Pulp pathology, Dental Pulp physiopathology, Dental Pulp Exposure, Dental Pulp Necrosis pathology, Dentin pathology, Dentin, Secondary pathology, Dentin, Secondary physiopathology, Granulation Tissue pathology, Granulation Tissue physiopathology, Male, Mandibular Nerve surgery, Nerve Degeneration, Nerve Fibers pathology, Neurons, Afferent pathology, Neutrophils pathology, Rats, Rats, Sprague-Dawley, Tissue Survival, Wound Healing, Dental Pulp injuries, Dental Pulp innervation, Nerve Fibers physiology, Neurons, Afferent physiology
- Abstract
Sensory nerve fibers that contain calcitonin gene-related peptide (CGRP) have been shown previously to sprout into inflamed tissue surrounding sites of pulpal injury. The sprouting fibers contain increased CGRP immunoreactivity (IR), and neuropeptide levels increase in the surrounding pulp. We compared denervated and innervated first mandibular molars of rats to determine whether the absence of sensory nerve fibers affected tissue survival and healing after pulp exposure. Significant differences were seen between innervated and denervated teeth six days after occlusal exposure, with more extensive necrosis in the denervated teeth, and less survival of vascular pulp. When exposures were on the side of the crown, there was no significant difference between the innervated and denervated teeth. Both the innervated and denervated teeth had begun to make reparative dentin and osteodentin by six days after tooth injury. This study shows that teeth with sensory denervation had an accelerated loss of pulp tissue following occlusal exposure compared with innervated teeth with similar injury.
- Published
- 1993
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14. Effects of inflammation on dental sensory nerves and vice versa.
- Author
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Byers MR
- Subjects
- Animals, Dental Pulp injuries, Nerve Growth Factors physiology, Dental Pulp innervation, Neurons, Afferent physiology, Pulpitis physiopathology
- Abstract
A brief review of the normal sensory innervation of teeth is presented, especially concerning the fibers that are immunoreactive (IR) for calcitonin gene-related peptide (CGRP). Numerous CGRP-IR fibers innervate coronal dentin at sites populated by primary odontoblasts and associated pulp cells that synthesize nerve growth factor (NGF). If the primary odontoblasts and adjacent pulp cells are lost as a consequence of injury, CGRP-IR dentinal innervation is greatly reduced. The responses of CGRP-IR nerve fibers to pulpal injury are reviewed. Those reactions show that pulpal sensory nerve fibers can alter the size, shape and immunoreactivity of their terminal branches in response to different stages of inflammation and healing.
- Published
- 1992
15. Reactions of sensory nerves to dental restorative procedures.
- Author
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Byers MR, Swift ML, and Wheeler EF
- Subjects
- Animals, Humans, Time Factors, Dental Pulp innervation, Dental Restoration, Permanent, Neurons, Afferent physiology
- Abstract
The reactions of sensory nerves to restorative procedures can be classified as immediate, early and late. For each of these, the neural response depends upon the severity of pulpal injury and the stages of inflammation and healing. Immediate responses in the first few minutes include destruction of nerve fibers in the injured dentin and pulp, hypersensitivity of surviving fibers, release of neuropeptides into the pulp and neurogenic inflammation. Early responses occur during the first few days after cavity preparation, with nerve fibers sprouting in the surviving pulp and gaining increased axonal transport and neuropeptide contents. Sensory fibers containing calcitonin gene related peptide (CGRP) greatly outnumber those with substance P (SP); but both types grow toward the surviving odontoblasts and associated pulp tissue surrounding the lesion. Later during subsequent weeks the nerve fibers accompany granulation tissue as it replaces acute inflammation; and nerve sprouting subsides when inflammation is reduced and when reparative dentin covers the injury site. An important response to tooth injury that may regulate nerve sprouting reactions is the increased production of nerve growth factor (NGF) by pulpal fibroblasts near the lesion. The timing of the nerve sprouting reactions suggests that they may contribute to tooth hypersensitivity after restorative procedures.
- Published
- 1992
16. Effects of dental trauma on pulpal and periodontal nerve morphology.
- Author
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Kvinnsland I, Heyeraas KJ, and Byers MR
- Subjects
- Animals, Calcitonin Gene-Related Peptide, Dental Occlusion, Traumatic pathology, Dentin innervation, Dentin, Secondary innervation, Dentin, Secondary pathology, Nerve Regeneration, Rats, Substance P, Tooth Replantation, Dental Pulp innervation, Neurons pathology, Periodontium innervation, Tooth Injuries
- Abstract
Regeneration and morphological changes in sensory peptidergic nerves in pulp and periodontium were studied after general dental trauma by means of immunohistochemistry. In control teeth also the total nerve supply was demonstrated by using antibody to the general neuronal marker, protein gene product (PGP)9.5. Two experimental rat models were used, i.e. tooth replantation and induced traumatic occlusion. Results from these studies are reviewed here. In the controls, the PGP9.5-immunoreactive(IR) nerve supply in pulp and periodontium was generally denser compared to CGRP-IR and SP-IR nerves. In the replanted teeth, regeneration of CGRP-IR nerves closely followed the pulp cell renewal. Density and distribution of the regenerated nerves showed two different patterns which seemed to depend on the capacity of the renewed pulp to form postoperative dentine. The nerve density never reached the same level as the controls. In teeth not able to form irregular dentine, the pulp was sparsely innervated and the pulp cavity was filled with innervated bone. Nerve responses in CGRP-IR and SP-IR nerves after unilateral induced traumatic occlusion in the first maxillary molar were studied at different observation periods up to 30 days. After 5 days, localized morphological nerve changes were found both in the pulp and periodontium within the total rat molar dentition. With increasing observation periods, the pulpal neural changes progressed and were extended to all pulpal areas compared to the periodontium, where the nerve responses remained localized to cervical and apical tissues throughout the experiment.
- Published
- 1992
17. Regeneration of calcitonin gene-related peptide immunoreactive nerves in replanted rat molars and their supporting tissues.
- Author
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Kvinnsland I, Heyeraas KJ, and Byers MR
- Subjects
- Animals, Axons physiology, Axons ultrastructure, Connective Tissue innervation, Connective Tissue pathology, Dental Pulp blood supply, Dental Pulp pathology, Dentin innervation, Dentin pathology, Female, Immunohistochemistry, Molar, Nerve Fibers ultrastructure, Neurons, Afferent ultrastructure, Periodontal Ligament innervation, Periodontal Ligament pathology, Periodontium pathology, Pulpitis pathology, Rats, Rats, Inbred Strains, Root Resorption pathology, Tooth Root innervation, Tooth Root pathology, Wound Healing, Calcitonin Gene-Related Peptide analysis, Dental Pulp innervation, Nerve Regeneration, Neurons, Afferent physiology, Periodontium innervation, Tooth Replantation
- Abstract
First maxillary right molars in 66 rats were elevated and replanted and the pulps allowed to regenerate for 1-90 days. The contralateral tooth served as control. Regeneration of nerves in the pulp and periodontium was studied by CGRP-immunohistochemistry and the avidin-biotin-peroxidase method. The pulp and periodontium of the controls were richly supplied with CGRP-labelled nerves. One day after replantation the pulp was completely devoid of CGRP-immunoreactive nerves. After 2 days, axon sprouts were present in the apical, regenerated pulp and in the periodontium. From 3-7 days CGRP-immunoreactive axons were regularly seen to have regenerated in front of the cellular inflammation in the pulp. After 10 days, the pulps were reinnervated up to the horns, although more sparsely than in the controls. From day 20-90 there was a marked divergence in pulpal healing: 17 pulps formed irregular postoperative dentine with a gradual increase in nerve density; 16 pulps remained sparsely innervated and were gradually replaced by bone. Root resorption was most extensive in the teeth with bone replacement of pulp. The soft tissue adjacent to extensive resorbing areas had many more CGRP-labelled axons than in the controls. The reinnervation of the regenerating pulp occurred at the same time as pulpal wound healing, but did not achieve the innervation density of the controls.
- Published
- 1991
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18. Effects of injury and inflammation on pulpal and periapical nerves.
- Author
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Byers MR, Taylor PE, Khayat BG, and Kimberly CL
- Subjects
- Animals, Dental Pulp injuries, Dentin innervation, Dentin Sensitivity physiopathology, Humans, Immunohistochemistry, Neuropeptides physiology, Periapical Tissue injuries, Rats, Calcitonin Gene-Related Peptide physiology, Dental Pulp innervation, Periapical Tissue innervation
- Abstract
Several studies dealing with the reactions of dental nerve fibers to injury and inflammation are reviewed in this article. The subgroup of dental nerve fibers that contains calcitonin gene-related peptide (CGRP) was examined by immunocytochemistry at various times (1 to 35 days) after one of three degrees of injury: (a) Mild: Four days after making shallow cavities into cervical dentin of first molars of anesthetized adult rats, we found that CGRP fibers had sprouted into the subjacent odontoblast layer and dentin, and then returned to normal by 3 wk. (b) Intermediate: If the cervical cavities were acid etched, we found damage to the odontoblast layer, microabscess formation, and sprouting of CGRP fibers near the abscess, with subsequent formation of reparative dentin and healing. (c) Severe: If the pulp was exposed, a variety of reactions could occur, the most prevalent of which was a severe necrosis leading to development of periapical lesions. Analysis of the progressive stages of pulpal abscess and necrosis showed sprouting CGRP nerve fibers (a) at the retreating interface between abscess and vital pulp; (b) in periapical areas during onset of lesions; and (c) around chronic abscesses in granulomatous periodontal tissues. These studies are discussed in relation to various dental clinical problems such as hypersensitive teeth, episodic toothache, early onset of periapical lesions, dental anesthesia, and possible roles for sensory fibers and neuropeptides in tissue defense and healing.
- Published
- 1990
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19. An immunocytochemical study of the morphological reaction of nerves containing calcitonin gene-related peptide to microabscess formation and healing in rat molars.
- Author
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Taylor PE and Byers MR
- Subjects
- Abscess pathology, Animals, Connective Tissue pathology, Dental Pulp pathology, Dentin, Secondary pathology, Immunohistochemistry, Male, Molar, Nerve Fibers chemistry, Nerve Fibers physiology, Nerve Regeneration physiology, Pulpitis pathology, Rats, Rats, Inbred Strains, Wound Healing, Abscess etiology, Calcitonin Gene-Related Peptide chemistry, Dental Pulp innervation, Dentin, Secondary physiology, Nerve Fibers pathology, Pulpitis etiology
- Abstract
Pulpal inflammation was induced by cutting a class V cavity to within 0.1-0.3 mm of the pulp on the mesial aspect of maxillary and mandibular first molars at the cervical line. The exposed dentine was briefly acid-etched and left open to the mouth until the animals were killed. Histological examination of teeth 4 days after injury showed microabscesses, blood vessel dilation and increased numbers of terminal nerve sprouts around the lesion and in radicular pulp and dentine. Specimens at 7, 11, 21 and 35 days after injury showed progressive healing of the lesions with the formation of reparative dentine and a coincident return to a normal patterns of innervation in the remaining pulp. Thus pulpal nerves are not static structures, but rather are capable of rapid change in response to inflammation. The morphological association of CGRP-immunoreactive nerve fibres with the edges of the healing lesions and with zones of reparative dentine suggests a role for these fibres and for the neuropeptide CGRP in the healing response of pulpal tissue.
- Published
- 1990
- Full Text
- View/download PDF
20. Dental nerve regeneration in rats. II. Autoradiographic studies of nerve regeneration to molar pulp and dentin.
- Author
-
Berger RL and Byers MR
- Subjects
- Alveolar Process innervation, Animals, Autoradiography, Axons ultrastructure, Gingiva innervation, Male, Nerve Degeneration, Rats, Rats, Inbred Strains, Dental Pulp innervation, Dentin innervation, Molar innervation, Nerve Regeneration
- Abstract
The autoradiographic technique was used to analyze the degeneration and regeneration of sensory nerves to rat molars and gingiva following cut or crush injury to the right inferior alveolar nerve. At 2 days after nerve injury there was almost complete denervation of the first molar, partial denervation of the second molar, and minimal effect on the innervation to the third molar and gingiva. The degree of sensory deficit and recovery for these same rats had been previously determined. Reinnervation of the first molar was analyzed in terms of axon number and location, intensity of axon labeling, and type of nerve injury. At 6 days, neither the cut injury nor crush injury rats had any reinnervation of their first molars. By 7 days, 3 of 4 rats had axons reinnervating first molars; in those teeth there was approximately one-fourth of the normal number of axons in the pulp, and very few axons in the dentin. These rats still had as large a molar sensory deficit as the 7 day rat and 6 day rats that had no reinnervation. By 3 weeks there were one-half to three-fourths of the normal axon numbers in the pulp, one-fourth to one-half of the normal axon numbers in dentin; and sensitivity was at least half-recovered. By 6 weeks, numbers of axons in the pulp and dentin were either normal or slightly less than normal; axons had grown back into dentin to the same depth as in normal teeth; and complete recovery of sensitivity had occurred. The regenerating axons had greater than normal labeling intensity at 1 week and 3 weeks in all rats. Those with the crush nerve injury had somewhat greater numbers of reinnervating axons at 1 week and 3 weeks than the cut injury rats. A structure-function comparison for the molars showed that return of sensitivity correlated with reinnervation of both pulp and dentin.
- Published
- 1983
- Full Text
- View/download PDF
21. Autoradiographic demonstration of ipsilateral and contralateral sensory nerve endings in cat dentin, pulp, and periodontium.
- Author
-
Byers MR and Matthews B
- Subjects
- Animals, Autoradiography, Axons cytology, Cats, Functional Laterality, Trigeminal Ganglion cytology, Dental Pulp innervation, Dentin innervation, Periodontium innervation, Sensory Receptor Cells anatomy & histology
- Abstract
In order to determine the location of sensory nerve ending in cat teeth, 3H-proline and 3H-leucine were injected into the left trigeminal ganglion of eight cats aged 6.5-10 months; 24 hours was allowed for axonal transport of radioactive protein to dental nerve endings, and the endings were then detected by autoradiography. The pulps of most ipsilateral (left) teeth contained some labeled axons. These axons ended in the odontoblastic layer and predentin of roots and crown; at the tip of the pulp horn of each cusp, nerve endings also extended as far as 150 micrometer into dentinal tubules. Labeled nerve endings were extremely rare in contralateral (right) teeth; only one tooth of 83 studied (eight cats) contained heavily labeled axons, and one other had faintly labeled axons. Both labeled contralateral teeth were central maxillary incisors. Their labeled axons were unbranched in the root and arborized in the crown to end among odontoblasts and many adjacent dentinal tubules. Labeled periodontal nerve endings were most numerous in the apical one-third of the ligament, with some endings extending as far as the gingiva. The nerve endings in the periodontal ligament were often clustered and appeared to end freely between the collagen bundles; their radioactivity varied in the same way as that of pulp nerves in the adjacent root.
- Published
- 1981
- Full Text
- View/download PDF
22. Sensory innervation of pulp and dentin in adult dog teeth as demonstrated by autoradiography.
- Author
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Byers MR, Närhi MV, and Dong WK
- Subjects
- Animals, Autoradiography, Dogs, Dental Pulp innervation, Dentin innervation, Neurons, Afferent ultrastructure
- Abstract
In order to study the location of sensory nerve fibers in dog teeth, we injected 3H-amino acids into the left trigeminal ganglion of 2 anesthetized adult dogs; we then waited 24 hours for axonal transport of labeled protein and prepared the fixed decalcified teeth for autoradiography. Heavily labeled sensory neurons were found in the maxillary and mandibular divisions of each injected ganglion and its peripheral nerves and central root. Numerous labeled axons were found entering dental roots; they arborized mostly in the crown to end in peripheral pulp or inner dentin. Some labeled fibers extended 150-175 microns into dentinal tubules, but most intradentinally labeled fibers were less than 100 microns long. The dentinal innervation was most concentrated in the crown, with autoradiographic label over more than 50% of the tubules at the tip of each pulp horn. Differences in innervation density for coronal, cervical, intercuspal, septal, radicular, and reparative dentin were analyzed. In some regions, labeled endings branched along the pulp-predentin border but did not enter the dentinal tubules. Electron microscopic autoradiograms were prepared to confirm specific labeling of nerve fibers and nerve endings, and to describe their ultrastructure and association with odontoblasts. The results show that labeled sensory fibers in dog teeth have an ultrastructure similar to that described previously for rat molars and for monkey and cat teeth. No specific junctions were found between labeled sensory fibers and odontoblasts, in agreement with previous studies of other teeth.
- Published
- 1987
- Full Text
- View/download PDF
23. Reactions of dental sensory innervation to injury and inflammation
- Author
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Byers, M. R., Taylor, P. E., Inoki, Reizo, Kudo, Teruo, and Olgart, Leif M.
- Published
- 1990
- Full Text
- View/download PDF
24. DENTAL INJURY MODELS: EXPERIMENTAL TOOLS FOR UNDERSTANDING NEUROINFLAMMATORY INTERACTIONS AND POLYMODAL NOCICEPTOR FUNCTIONS.
- Author
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Byers, M. R. and Narhi, M. V. O.
- Subjects
DENTAL research ,TISSUES ,INFLAMMATION ,WOUND healing ,NOCICEPTORS ,SENSORY receptors ,DENTAL pulp ,DENTAL resins - Abstract
Recent research has shown that peripheral mechanisms of pain are much more complex than previously thought, and they differ for acutely injured normal tissues compared with chronic inflammation or neuropathic (nerve injury) pain. The purpose of the present review is to describe uses of dental injury models as experimental tools for understanding the normal functions of polymodal nociceptive nerves in healthy tissues, their neuroinflammatory interactions, and their roles in healing. A brief review of normal dental innervation and its interactions with healthy pulp tissue will be presented first, as a framework for understanding the changes that occur after injury. Then, the different types of dental injury that allow gradation of the extent of tissue damage will be described, along with the degree and duration of inflammation, the types of reactions in the trigeminal ganglion and brainstem, and the type of healing. The dental injury models have some unique features compared with neuroinflammation paradigms that affect other peripheral tissues such as skin, viscera, and joints. Peripheral inflammation models can all be contrasted to nerve injury studies that produce a different kind of neuroplasticity and neuropathic pain. Each of these models provides different insights about the normal and pathologic functions of peripheral nerve fibers and their effects on tissue homeostasis, inflammation, and wound healing. The physical confinement of dental pulp and its innervation within the tooth, the high incidence of polymodal A-delta and C-fibers in pulp and dentin, and the somatotopic organization of the trigeminal ganglion provide some special advantages for experimental design when dental injury models are used for the study of neuroinflammatory interactions. [ABSTRACT FROM AUTHOR]
- Published
- 1999
- Full Text
- View/download PDF
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