著者
Kazuhiko Hara Takahiro Shinozaki Akiko Okada-Ogawa Yumiko Matsukawa Ko Dezawa Yuka Nakaya Jui-Yen Chen Noboru Noma Shunichi Oka Koichi Iwata Yoshiki Imamura
出版者
Nihon University School of Dentistry
雑誌
Journal of Oral Science (ISSN:13434934)
巻号頁・発行日
vol.58, no.2, pp.195-204, 2016 (Released:2016-06-25)
参考文献数
44
被引用文献数
7 25

We investigated the temporal association between temporomandibular disorders (TMD)-related symptoms and headache during TMD treatment for patients who fulfilled the diagnostic criteria for headache attributed to TMD (HATMD) specified in the Diagnostic criteria for TMD (DC/TMD) and International classification of headache disorders (ICHD)-3 beta. The study enrolled 34 patients with HATMD induced by masticatory myofascial pain but not by temporomandibular arthralgia. Facial pain intensity, the pressure pain threshold of pericranial muscles, and maximum unassisted opening of the jaw were assessed at an initial examination and before and after physical therapy. The intensity and frequency of headache episodes and tooth contact ratio were also recorded before and after the intervention. Headache intensity and frequency significantly decreased, and these reductions were temporally related to improvements in facial pain intensity, maximum unassisted opening, and pressure pain threshold during TMD treatment. Linear regression analysis showed significant correlations between facial pain intensity and headache intensity and between tooth contact ratio and pressure pain threshold. Among patients who fulfilled the DC/TMD and ICHD-3 beta diagnostic criteria for HATMD, headache improved during TMD treatment, and the improvement was temporally related to amelioration of TMD symptoms. These findings suggest that sensitization in the central and peripheral nervous systems is responsible for HATMD. (J Oral Sci 58, 195-204, 2016)
著者
Naoki Murakami Kenji Yoshikawa Kohei Tsukada Noriaki Kamio Yoshinori Hayashi Suzuro Hitomi Yuki Kimura Ikuko Shibuta Ayaka Osada Shuichi Sato Koichi Iwata Masamichi Shinoda
出版者
Nihon University School of Dentistry
雑誌
Journal of Oral Science (ISSN:13434934)
巻号頁・発行日
pp.21-0483, (Released:2021-12-29)
参考文献数
29
被引用文献数
1

Purpose: Periodontitis progresses with chronic inflammation, without periodontal pain. However, the underlying mechanisms are not well known. Here, the involvement of butyric acid (BA) in periodontal pain sensitivity in Porphyromonas gingivalis (P. gingivalis)-induced periodontitis was examined.Methods: P. gingivalis was inoculated into the ligature which was tied around the molar (P. gingivalis-L) and the gingival mechanical head withdrawal threshold (MHWT) was measured. Following P. gingivalis-L, the expressions of orphan G protein-coupled receptor 41 (GPR41) in trigeminal ganglion (TG) neurons were examined. The amount of gingival BA was analyzed following the P. gingivalis-L and the changes in the MHWT in complete Freund’s adjuvant (CFA)-injected gingival tissue by gingival BA were examined. The changes in the MHWT following P. gingivalis-L by gingival GPR41 antagonist (HA) were examined.Results: No change in the MHWT was observed, GPR41-immunoreactive TG neurons were increased following P. gingivalis-L. The gingival BA amount increased following P. gingivalis-L, and the gingival BA suppressed the decrease in MHWT following CFA. HA decreased MHWT following P. gingivalis-L.Conclusion: Gingival BA modulates periodontal mechanical nociception via GPR41 signaling in P. gingivalis-L-induced periodontitis.
著者
Shumpei Unno Masamichi Shinoda Kumi Soma Asako Kubo Barry J Sessle Tomoyuki Matsui Masatoshi Ando Junichi Asaka Katsuhiko Otsuki Hisashi Yonemoto Hiroki Onose Kousuke Sakanashi Koichi Iwata
出版者
Nihon University School of Dentistry
雑誌
Journal of Oral Science (ISSN:13434934)
巻号頁・発行日
pp.19-0512, (Released:2020-08-01)
参考文献数
31

To investigate neuronal activity involved in responses to noxious stimuli in conscious monkeys, the animals were subjected to a task that required them to detect a small change in facial skin temperature or light (second temperature: T2, second light: V2) relative to an initial condition (T1 or V1), and to detect changes in V2 along with a heat task. Recordings were obtained from 57 neurons in the ventral premotor cortex (PMv) during the heat or light detection task. T1 neurons and T2 neurons showed increased activity only during T1 or T2, and T1/T2 neurons were activated by both T1 and T2 stimuli. T1/T2 neurons showed an increase in firing at higher T1 temperatures, whereas T1 neurons did not. About half of the non-light/heat-sensitive T1/T2 neurons showed increased firing at higher T2 temperatures, whereas T2 neurons showed no such increase. The heat responses of heat-sensitive PMv neurons were significantly suppressed when monkeys shifted their attention from heat to light. The present findings suggest that heat-sensitive PMv neurons may be involved in motor responses to noxious heat, whereas light/heat-PMv neurons may be involved in emotional and motivational aspects of pain and inappropriate motor responses to allow escape from noxious stimuli.
著者
Yoshiki Imamura Akiko Okada-Ogawa Noboru Noma Takahiro Shinozaki Kosuke Watanabe Ryutaro Kohashi Masamichi Shinoda Akihiko Wada Osamu Abe Koichi Iwata
出版者
Nihon University School of Dentistry
雑誌
Journal of Oral Science (ISSN:13434934)
巻号頁・発行日
pp.19-0459, (Released:2020-03-11)
参考文献数
87
被引用文献数
7

Burning mouth syndrome (BMS) is one of the most frequently seen idiopathic pain conditions in a dental setting. Peri- and postmenopausal women are most frequently affected, and patients who experience BMS complain of persistent burning pain mainly at the tip and the bilateral border of the tongue. Recent studies have assessed whether BMS is a neuropathic pain condition, based on morphologic changes in biopsied tongue specimens, and whether there are abnormal pain responses in patients with this disease. Somatosensory studies have reported some abnormal findings in sensory and pain detection thresholds with inconsistency; however, the most distinct finding was exaggerated responses to painful stimuli. Imaging and electrophysiologic studies have suggested the possibility of dysregulation of the pain-modulating system in the central nervous system, which may explain the enhanced pain responses despite the lack of typical responses toward quantitative sensory tests. Basic studies have suggested the possible involvement of neuroprotective steroids, although the underlying mechanisms of this condition have not been elucidated. Experimental studies are looking for preferable supportive therapies for BMS patients despite the obscure pathogenesis.
著者
Masamichi Shinoda Yoshinori Hayashi Asako Kubo Koichi Iwata
出版者
Nihon University School of Dentistry
雑誌
Journal of Oral Science (ISSN:13434934)
巻号頁・発行日
pp.19-0373, (Released:2020-03-04)
参考文献数
86
被引用文献数
16

Nociceptive stimuli to the orofacial region are typically received by the peripheral terminal of trigeminal ganglion (TG) neurons, and noxious orofacial information is subsequently conveyed to the trigeminal spinal subnucleus caudalis and the upper cervical spinal cord (C1-C2). This information is further transmitted to the cortical somatosensory regions and limbic system via the thalamus, which then leads to the perception of pain. It is a well-established fact that the presence of abnormal pain in the orofacial region is etiologically associated with neuroplastic changes that may occur at any point in the pain transmission pathway from the peripheral to the central nervous system (CNS). Recently, several studies have reported that functional plastic changes in a large number of cells, including TG neurons, glial cells (satellite cells, microglia, and astrocytes), and immune cells (macrophages and neutrophils), contribute to the sensitization and disinhibition of neurons in the peripheral and CNS, which results in orofacial pain hypersensitivity.
著者
Jui Yen Chen Asako Kubo Masamichi Shinoda Akiko Okada-Ogawa Yoshiki Imamura Koichi Iwata
出版者
Nihon University School of Dentistry
雑誌
Journal of Oral Science (ISSN:13434934)
巻号頁・発行日
vol.62, no.1, pp.13-17, 2020 (Released:2020-01-29)
参考文献数
22
被引用文献数
7

Although xerostomia can cause persistent oral pain, the mechanisms underlying such pain are not well understood. To evaluate whether a phosphorylated p38 (pp38)-TRPV4 mechanism in trigeminal ganglion (TG) neurons has a role in mechanical hyperalgesia of dry tongue, a rat model of dry tongue was used to study the nocifensive reflex and pp38 and TRPV4 expression in TG neurons. The head-withdrawal reflex threshold for mechanical stimulation of the tongue was significantly lower in dry-tongue rats than in sham rats. The numbers of TRPV4- and pp38-immunoreactive cells in the TG were significantly higher in dry-tongue rats than in sham rats. Many TRPV4-IR cells were also pp38-immunoreactive. The number of TRPV1-IR cells was unchanged in the TG after induction of tongue dryness. Local injection of a TRPV4 blocker attenuated tongue mechanical hypersensitivity in dry-tongue rats. Intraganglionic injection of a selective p38 MAP kinase inhibitor eliminated tongue hypersensitivity in dry-tongue rats and suppressed TRPV4 expression in TG neurons. The present findings suggest that TRPV4 activation via p38 phosphorylation in TG neurons is involved in mechanical hypersensitivity associated with dry tongue. These mechanisms may have a role in pain associated with xerostomia.
著者
Shinji Okada Ayano Katagiri Hiroto Saito Jun Lee Kinuyo Ohara Toshimitsu Iinuma Koichi Iwata
出版者
Nihon University School of Dentistry
雑誌
Journal of Oral Science (ISSN:13434934)
巻号頁・発行日
vol.61, no.2, pp.370-378, 2019 (Released:2019-06-18)
参考文献数
40
被引用文献数
10

Peripheral nerve injury can induce neuroplastic changes in the central nervous system and result in neuropathic pain. This study investigated functional involvement in dorsal paratrigeminal nucleus (dPa5) and nucleus tractus solitarii (NTS) neurons projecting to the parabrachial nucleus (PBN) after trigeminal nerve injury. Anatomical quantification was performed based on phosphorylated extracellular signal-regulated kinase (pERK) expression underlying orofacial neuropathic pain associated with infraorbital nerve chronic constriction injury (ION-CCI) in rats. ION-CCI rats exhibited heat and mechanical hypersensitivity in the ipsilateral upper lip. After injection of retrograde tracer fluorogold (FG) into the contralateral PBN, ION-CCI rats received capsaicin or noxious mechanical stimulation to the upper lip. The total number of FG-labeled neurons in dPa5 and NTS did not change after ION-CCI, and pERK expression in dPa5 did not differ between sham and ION-CCI rats. In the NTS contralateral to ION-CCI, the number of pERK-immunoreactive neurons and percentage of pERK-immunoreactive FG-labeled PBN projection neurons were increased after capsaicin stimulation in ION-CCI rats. The present findings suggest that enhanced noxious inputs from the NTS to the PBN after trigeminal nerve injury modulates PBN neuron activity, which accompanies the affective components of orofacial neuropathic pain.
著者
Shinji Okada Hiroto Saito Yutaka Matsuura Lou Mikuzuki Shiori Sugawara Hiroki Onose Junichi Asaka Kinuyo Ohara Jun Lee Toshimitsu Iinuma Ayano Katagiri Koichi Iwata
出版者
Nihon University School of Dentistry
雑誌
Journal of Oral Science (ISSN:13434934)
巻号頁・発行日
vol.61, no.1, pp.146-155, 2019 (Released:2019-03-28)
参考文献数
77
被引用文献数
2

Bright light stimulation of the eye activates trigeminal subnucleus caudalis (Vc) neurons in rats. Sensory information is conveyed to the Vc via the trigeminal ganglion (TG). Thus, it is likely that TG neurons respond to photic stimulation and are involved in photic hypersensitivity. However, the mechanisms underlying this process are unclear. Therefore, the hypothesis in this study is bright light stimulation enhances the excitability of TG neurons involved in photic hypersensitivity. Expressions of calcitonin gene-related peptide (CGRP) and neuronal nitric oxide synthase (nNOS) were significantly higher in TG neurons from 5 min to 12 h after photic stimulation of the eye. Phosphorylation of extracellular signal-regulated kinase1/2 (pERK1/2) was enhanced in TG neurons within 5 min after photic stimulation, while pERK1/2 immunoreactivity in satellite glial cells (SGCs) persisted for more than 12 h after the stimulus. Activation of SGCs was observed from 5 min to 2 h. Expression of CGRP, nNOS, and pERK1/2 was observed in small and medium TG neurons, and activation of SGCs and pERK1/2-immunoreactive SGCs encircling large TG neurons was accelerated after stimulation. These results suggest that upregulation of CGRP, nNOS, and pERK1/2 within the TG is involved in photic hypersensitivity.
著者
Tatsuro Suzuki Masahiro Kondo Ikuko Shibuta Hidekazu Nagashima Naoyuki Sugano Shuichi Sato Koichi Iwata
出版者
Nihon University School of Dentistry
雑誌
Journal of Oral Science (ISSN:13434934)
巻号頁・発行日
vol.60, no.4, pp.500-506, 2018 (Released:2018-12-27)
参考文献数
25
被引用文献数
1

The inferior alveolar nerve (IAN) comprises several types of sensory fibers. To clarify whether each type of primary afferent is regenerated comparably after injury, we developed a model of complete IAN transection (IANX) in mice. A retrograde tracer, fluoro-gold, injected into the mental skin was transferred to the cell bodies of a subset of isolectin B4 (IB4)-binding (non-peptidergic C) or CGRP-positive (peptidergic C) neurons at 2 weeks post-axotomy, indicating that the injured C afferents had regenerated anatomically. IANX led to a decrease of IB4-binding and CGRP immunoreactivity (IR) in the trigeminal ganglion (TG) and within the trigeminal spinal subnucleus caudalis (Vc) (i.e. terminals of the central branch of TG neurons). Two weeks after IANX, the reduction in IB4-binding activity and CGRP expression in the TG recovered to the control level; however, IB4-binding within the Vc did not, suggesting that central branch non-peptidergic neurons remained impaired. Two weeks after IANX, pinching or heat stimulus-induced extracellular signal-regulated kinase phosphorylation (pERK) was restored to the control level, but in the case of pinch stimulation the distribution pattern of pERK-IR cells was altered in the Vc. Taken together, our results support the possibility that peptidergic neurons regenerate more efficiently than non-peptidergic neurons after trigeminal nerve injury.
著者
Hiroki Komiya Kohei Shimizu Kae Ishii Hiroshi Kudo Teinosuke Okamura Kohei Kanno Masamichi Shinoda Bunnai Ogiso Koichi Iwata
出版者
Nihon University School of Dentistry
雑誌
Journal of Oral Science (ISSN:13434934)
巻号頁・発行日
vol.60, no.4, pp.493-499, 2018 (Released:2018-12-27)
参考文献数
23
被引用文献数
28

Pulpitis often causes referred pain in opposing teeth. However, the precise mechanism underlying ectopic pain associated with tooth-pulp inflammation remains unclear. We performed the present study to test the hypothesis that functional interactions between satellite glial cells (SGCs) and trigeminal ganglion (TG) neurons are involved in ectopic orofacial pain associated with tooth-pulp inflammation. Digastric muscle electromyograph (D-EMG) activity elicited by administration of capsaicin into the upper second molar pulp (U2) was analyzed to evaluate noxious reflex responses. D-EMG activity was significantly increased in rats with lower first molar (L1) inflammation relative to saline-treated rats. Significantly increased expression of glial fibrillary acid protein (GFAP), a marker of activated glial cells, and connexin 43 (Cx43), a gap-junction protein, was observed in activated SGCs surrounding U2-innervating TG-neurons after L1-pulp inflammation. Daily administration of Gap26, a Cx43-inhibiting mimetic peptide, into the TG significantly suppressed capsaicin-induced D-EMG activity enhancement and reduced the percentage of fluorogold-labeled (U2-innervated) cells that were surrounded by GFAP-immunoreactive (IR) and Cx43-IR cells after L1-pulp inflammation. These findings indicate that tooth-pulp inflammation induces SGC activation and subsequent spread of SGC activation in the TG via Cx43-containing gap junctions. Thus, remote neuron excitability becomes enhanced in the TG following tooth-pulp inflammation, resulting in ectopic tooth-pulp pain in the contralateral tooth.
著者
Jun Lee Chisato Yamate Masato Taira Masamichi Shinoda Kentaro Urata Mitsuru Maruno Reio Ito Hiroto Saito Nobuhito Gionhaku Toshimitsu Iinuma Koichi Iwata
出版者
Nihon University School of Dentistry
雑誌
Journal of Oral Science (ISSN:13434934)
巻号頁・発行日
pp.17-0238, (Released:2018-05-24)
参考文献数
34
被引用文献数
2

Prefrontal cortex activity is modulated by flavor and taste stimuli and changes during swallowing. We hypothesized that changes in the modulation of prefrontal cortex activity by flavor and taste were associated with swallowing movement and evaluated brain activity during swallowing in patients with dysphagia. To evaluate prefrontal cortex activity in dysphagia patients during swallowing, change in oxidized hemoglobin (z-score) was measured with near-infrared spectroscopy while dysphagia patients and healthy controls swallowed sweetened/unsweetened and flavored/unflavored jelly. Total z-scores were positive during swallowing of flavored/unsweetened jelly and negative during swallowing of unflavored/sweetened jelly in controls but negative during swallowing of sweetened/unsweetened and flavored/unflavored jelly in dysphagia patients. These findings suggest that taste and flavor during food swallowing are associated with positive and negative z-scores, respectively. Change in negative and positive z-scores may be useful in evaluating brain activity of dysphagia patients during swallowing of sweetened and unsweetened food.
著者
Tetsuro Watase Kohei Shimizu Hiroki Komiya Kinuyo Ohara Koichi Iwata Bunnai Ogiso
出版者
Nihon University School of Dentistry
雑誌
Journal of Oral Science (ISSN:13434934)
巻号頁・発行日
pp.16-0854, (Released:2018-02-26)
参考文献数
21
被引用文献数
9

A study was conducted to evaluate the mechanisms underlying ectopic orofacial pain associated with tooth pulp inflammation in rats. We observed a significant decrease in the head withdrawal threshold (HWT) response to mechanical and heat stimuli applied to the ipsilateral facial skin upon application of complete Freund’s adjuvant (CFA) to the upper first molar (M1TP) in comparison to application of vehicle. A large number of trigeminal ganglion (TG) neurons showed transient receptor potential vanilloid 1 (TRPV1) immunoreactivity (IR), and some of them were retrogradely labeled with fluorogold injected into the facial skin. A large number of cells showing IR for glial fibrillary acidic protein (GFAP) were observed in the 2nd compared to the 1st or 3rd branch regions of the TG, and TG cells innervating the facial skin were also surrounded by GFAP-IR cells. After administration of TRPV1 antagonist into the facial skin of M1TP CFA-treated rats, the decrease of HWTs in response to mechanical and heat stimulation of the facial skin was significantly reversed. The present findings suggest that the excitability of TG neurons is enhanced upon tooth pulp inflammation, leading to overexpression of TRPV1 in TG neurons innervating the facial skin, and that satellite glial cells are also activated, resulting in the development of ectopic orofacial pain.
著者
Hidekazu Nagashima Masamichi Shinoda Kuniya Honda Noriaki Kamio Akira Hasuike Naoyuki Sugano Yoshinori Arai Shuichi Sato Koichi Iwata
出版者
日本大学歯学部
雑誌
Journal of Oral Science (ISSN:13434934)
巻号頁・発行日
pp.16-0830, (Released:2017-10-31)
参考文献数
45
被引用文献数
13

Periodontitis caused by bacterial infection gradually progresses accompanied by periodontal tissue destruction. As a result, teeth lose their supporting structures, and this leads to tooth exfoliation. CXC-chemokine receptor 4 (CXCR4) is known to be expressed in lymphocytes, fibroblasts and osteoclasts in periodontal tissues, suggesting that periodontal CXCR4 signaling contributes to alveolar bone resorption in the milieu of periodontitis. However, the role of CXCR4 signaling in the pathogenesis of periodontitis has remained unknown. We established a mouse model of periodontitis by inoculation of Porphyromonas gingivalis (P.g.) into a silk ligature placed around the maxillary molar. Although there was no significant difference in the mechanical sensitivity in the periodontal tissue between P.g. treatment and sham treatment during the experimental period, mechanical allodynia in the periodontal tissue was induced after gingival injection of complete Freund’s adjuvant compared with that resulting from sham and P.g. treatment alone. Moreover, CXCR4 neutralization in the periodontal tissue following P.g. treatment enhanced periodontal inflammatory cell infiltration and depressed alveolar bone resorption. These findings suggest that periodontal CXCR4 signaling in several cell types in P.g.-induced periodontal inflammation depresses alveolar bone resorption in periodontitis. CXCR4 signaling might be a target for therapeutic intervention to prevent alveolar bone resorption in periodontitis.
著者
Koichi Iwata Ayano Katagiri Masamichi Shinoda
出版者
日本大学歯学部
雑誌
Journal of Oral Science (ISSN:13434934)
巻号頁・発行日
vol.59, no.2, pp.173-175, 2017 (Released:2017-06-22)
参考文献数
26
被引用文献数
24

Excitability of neurons in the trigeminal ganglion (TG), trigeminal spinal subnucleus caudalis (Vc), and upper cervical spinal cord (C1-C2) is greatly enhanced after orofacial inflammation and trigeminal nerve injury, and TG, Vc, and C1-C2 neurons remain sensitized long after such episodes. Sensitized neurons generate various molecules, which are released from nociceptive neurons in these areas and are involved in modulating the excitability of TG, Vc, and C1-C2 nociceptive neurons. Hyperexcitable nociceptive neurons also activate satellite glial cells in the TG and microglial cells and astrocytes in the Vc and C1-C2. Glial cell activation spreads throughout the TG, Vc, and C1-C2 and triggers the release of various molecules involved in modulating nociceptive neurons in TG, Vc, and C1-C2 neurons. These findings suggest that functional interaction between neurons and glial cells is critical in persistent orofacial pain associated with orofacial inflammation and trigeminal nerve injury.