Role of Neuron-Glial Interaction Mediated by IL-1ß in Ectopic Tooth Pain.

Although many reports have demonstrated that ectopic pain develops in the orofacial region following tooth pulp inflammation, which often causes misdiagnosis and inappropriate treatment for patients with pulpitis, the precise mechanism remains unknown. In the present study, we hypothesized that the functional interaction between satellite glial cells and neurons mediated by interleukin 1ß (IL-1ß) in the trigeminal ganglion (TG) is involved in ectopic orofacial pain associated with tooth pulp inflammation. The digastric muscle electromyogram (D-EMG) activity elicited by capsaicin administration into the maxillary second molar tooth pulp was analyzed to evaluate the noxious reflex and was significantly increased in rats with inflammation of the maxillary first molar (M1) versus rats injected with saline. A significant increase in the expression of connexin43 (Cx43), a gap junction containing protein, was observed in activated satellite glial cells surrounding second molar-innervating neurons in the TG after M1 pulpitis. Daily administration of Gap26, a Cx43 mimetic peptide and inhibitor, in the TG significantly suppressed the enhancement of capsaicin-induced D-EMG activity and the percentage of Fluoro-Gold (FG)-labeled cells encircled by glial fibrillary acid protein-immunoreactive (IR) + Cx43-IR cells after M1 pulp inflammation ( P < 0.01). The percentage of FG-labeled cells encircled by glial fibrillary acid protein-IR + IL-1ß-IR cells, IL-1 type I receptor-IR cells labeled with FG, and TRPV1-IR cells labeled with FG significantly increased after M1 pulp inflammation ( P < 0.01). Daily administration of IL-1ra, an IL-1 receptor antagonist, into the TG significantly reduced the enhancement of capsaicin-induced D-EMG activity and the percentage of TRPV1-IR neurons labeled with FG after M1 pulp inflammation ( P < 0.01). The present findings suggest that satellite glial cell is activated in the TG via activated gap junctions composed of Cx43 following tooth pulp inflammation, which leads to the hyperactivation of remote neurons via IL-1ß mechanisms and results in ectopic tooth pulp pain in the adjacent tooth.

Quantitative evaluation of oral function in acute and recovery phase of idiopathic facial palsy; a preliminary controlled study.

OBJECTIVES: Patients with peripheral facial palsy frequently complain of fluid leakage and food retention during meals. We investigated oral function during eating in adults with peripheral facial palsy. DESIGN: A prospective two-phase controlled observational study. SETTING: Data were collected at the ENT clinic in Nihon University Itabashi Hospital (patients) and Nihon University Dental Hospital (controls) between September 2009 and August 2011 and analysed at the Department of Oral Diagnostic Sciences in Nihon University School of Dentistry. PARTICIPANTS: Fourteen patients with acute idiopathic facial palsy and 14 controls completed Study 1. Sixteen patients with acute idiopathic facial palsy and 16 controls completed Study 2. MAIN OUTCOME MEASURES: In Study 1, oral vestibular cleansing capability was assessed by measuring the amount of rice remaining in the oral vestibule after mastication. In Study 2, masticatory efficiency was evaluated by measuring glucose eluted from gummy jelly during chewing. These oral functions were observed at the first visit and final visit (after patients with facial palsy had recovered). RESULTS: Oral vestibular cleansing capability at the first visit was significantly decreased by facial palsy (P < 0.001 versus healthy volunteers and P < 0.001 versus contralateral side) but recovered as facial muscular function improved (P = 0.034). There was a significant correlation between improvement in paralysis and decreased food retention (r = -0.528, P = 0.010). At the first visit, masticatory efficiency on the affected side was significantly lower than that of controls (P = 0.002) but had mostly recovered after resolution of facial palsy (P = 0.033). CONCLUSIONS: Oral functions were decreased by peripheral facial palsy. Oral vestibular cleansing capability was more significantly associated than masticatory efficiency with facial muscle function. Our data suggest that peripheral facial palsy impairs eating and worsens oral hygiene, which may result in oral disease.

Interaction of IL-1ß and P2X(3) receptor in pathologic masseter muscle pain.

The exact mechanism underlying chronic masseter muscle pain, a conspicuous symptom in temporomandibular disorder, remains unclear. We investigated whether expression of P2X3 receptor (P2X3R) is involved in mechanical hyperalgesia after contraction of masseter muscle (CMM). As compared with sham rats, the head-withdrawal threshold (HWT) to mechanical pressure stimulation of masseter muscle (MM) (but not after similar stimulation of facial skin) was significantly lower, and IL-1ß level was significantly higher, in CMM rats on day 7 after CMM. The mean percentage of FG-labeled P2X3R-positive neurons was significantly increased in TG following successive IL-1ß injections into the MM for 7 days. Successive administration of an IL-1ß receptor-antagonist into the MM attenuated the increase of P2X3-IR cells in the TG. ATP release from MM after 300-g pressure stimulation of MM was also significantly enhanced after CMM. Administration into MM of the selective P2X3,2/3 receptor antagonist A-317491 attenuated the decrement of HWT in CMM rats. A significant increase in HWT was also observed at 30 min after A-317491 (60 µg) injection in IL-1ß-injected rats. These findings suggest that P2X3R expression associated with enhanced IL-1ß expression and ATP release in MM has a possible important role in MM mechanical hyperalgesia after excessive muscular contraction.

Activation of the AKT/cyclin D1/Cdk4 survival signaling pathway in radioresistant cancer stem cells.

Radioresistance, which is a major cause of failure of radiotherapy (RT), is proposed as one of the intrinsic characteristics of cancer stem cells (CSCs) whose unique DNA damage response (DDR), efficient DNA repair and resistance to apoptosis are thought to confer the phenotype. We have isolated surviving CSCs by exposure to long-term fractionated radiation for 82 days from HepG2 and A172 cells (82FR-31NR cells). 82FR-31NR cells exhibited CSC properties, such as high expression of CSC marker CD133 and the ABC transporters (MDR1 and BCRP1), and high tumorigenic potential after transplantation into nude mice. The advantage of our isolated CSCs is that they can proliferate in as the same growth medium as that of parental cells without loss of CSC properties. Therefore, we can analyze DDR of non-stem cells and CSCs without any influences caused by different culture conditions. 82FR-31NR cells showed efficient DNA repair of radiation-induced DNA damage and radioresistance with activation of the AKT/cyclin D1 survival signaling pathway. In contrast, DNA damage persisted for a long time after irradiation in parental cells compared with isolated CSCs. Persisted DNA damage induced apoptosis in parental cells without activation of the AKT/cyclin D1 pathway. Therefore, inhibition of the AKT/cyclin D1 pathway by an AKT inhibitor, API-2, or cyclin D1 siRNA resulted in a loss of efficient DNA repair and radiosensitization of 82FR-31NR cells. Furthermore, knockdown of Cdk4 by its siRNA or a Cdk4 inhibitor was sufficient to suppress radioresistance of CSCs. In this study, we present a newly discovered DDR regarding the AKT/cyclin D1/Cdk4 pathway in response to radiation in CSCs. Combination of fractionated RT and reagents targeting the AKT/cyclin D1/Cdk4 pathway to eradicate CSCs would be effective therapeutic modality.

[A comparison with Dardik graft and Mindich graft on arterial bypass].

Arterial reconstruction using human umbilical cord vein graft as a vascular prosthesis was carried out in 24 patients, 26 legs, with arteriosclerosis obliterans. Dardik grafts were used in 13 legs and Mindich grafts in 13 legs. Twenty-six operations were divided into two groups; one with the proximal anastomosis above the femoral artery (proximal group) and the other with the proximal anastomosis below the femoral artery (distal group). Postoperative evaluation of all patients was performed at intervals of one to twenty-two months. To make the determination of graft patency, at least, it was required that the graft pulse was palpable. Cumulative patency rates were 54% and 69% in the Mindich grafts and Darkik grafts, respectively. In the proximal group, patency rates were 60% and 50% in Mindich grafts and Dardik grafts, respectively. While in the distal group, patency rates were 37.5% and 78% in Mindich grafts and Dardik grafts, respectively. The causes of the graft obstruction were as follows: 1) graft infection in 4 (2 with Mindich and 2 with Dardik grafts) 2) pseudointimal hyperplasia of the distal anastomosis in 4 with Mindich graft, 3) progression of atherosclerosis in one case with Dardik graft, and 4) substandard Dardik graft in one. It was concluded that Dardik graft should be used as first choice when compared with Mindich graft and these grafts should not be used easily, since these grafts were apt to be infected.