Jaw Exercise Therapy and Psychoeducation to Reduce Oral Parafunctional Activities for the Management of Persistent Dentoalveolar Pain.

Objective: To retrospectively analyze the effects of our original combination therapy treatment on patients with nonodontogenic persistent dentoalveolar pain. Methods: Twenty-one patients suffering from persistent dentoalveolar pain (nineteen females and two males; mean age ± standard deviation: 55.7 ± 19.6 years) participated in this study. They were treated with a therapy combination of jaw exercise and psychoeducation to reduce oral parafunctional activities every month. The intensity of pain in these subjects was evaluated using a numerical rating scale (NRS) before and after treatment. Results: The NRSs at the baseline ranged from 5 to 10 (median, 8), from 0 to 10 (median, 2) at one month after treatment, from 0 to 10 (median, 1) at three months after treatment, and from 0 to 10 (median, 0) at the end of treatment. Pain intensity after treatment improved significantly. Conclusion: There was a significant reduction in pain after our combination of therapies as nonpharmacological treatments, and therefore this treatment could be useful in the management of NPDP patients.

Analysis of follow-up data from an outpatient pain management program for refractory chronic pain.

BACKGROUND: Numerous reports indicate that multifaceted pain management programs based on cognitive-behavioral principles are associated with clinically meaningful long-term improvements in chronic pain. However, this has not yet been investigated in Japan. This study investigated the effects of a multifaceted pain management program in Japanese patients with chronic pain, both immediately after the program and 6 months thereafter. METHODS: A total of 96 patients, 37 male and 59 female (mean age 63.8 years) experiencing treatment difficulties and suffering from intractable pain for more than 6 months were enrolled in the study. The programs were conducted with groups of 5-7 patients who met weekly for 9 weeks. Weekly sessions of approximately 2 h in duration incorporating a combination of lectures and exercise were conducted. Several measures related to pain and physical function were assessed at the start of the program, the end of the program, and 6 months after completion of the program. The resulting data were analyzed via Wilcoxon signed-rank test, and 'r' estimated by effect size was also assessed. RESULTS: Of the 96 initial participants, 11 dropped out during the program and 85 completed it. Thereafter, we evaluated 62 subjects at 6 months after the program, while 23 could not be evaluated at that time-point. Pain intensity upon moving, catastrophizing scores, and pain disability scores showed good improvements at the 6-month follow-up, with large efficacy (r > 0.5). Moving capacity and 6-min walking distance also showed good improvements with large efficacy, both at the end of the program and at the 6-month follow-up (r > 0.5). CONCLUSIONS: A multifaceted pain-management program based on cognitive-behavioral principles was effective in Japanese patients with chronic pain, resulting in improved long-term clinical outcomes.

A subset of cerebrovascular pericytes originates from mature macrophages in the very early phase of vascular development in CNS.

Pericytes are believed to originate from either mesenchymal or neural crest cells. It has recently been reported that pericytes play important roles in the central nervous system (CNS) by regulating blood-brain barrier homeostasis and blood flow at the capillary level. However, the origin of CNS microvascular pericytes and the mechanism of their recruitment remain unknown. Here, we show a new source of cerebrovascular pericytes during neurogenesis. In the CNS of embryonic day 10.5 mouse embryos, CD31+F4/80+ hematopoietic lineage cells were observed in the avascular region around the dorsal midline of the developing midbrain. These cells expressed additional macrophage markers such as CD206 and CD11b. Moreover, the CD31+F4/80+ cells phagocytosed apoptotic cells as functionally matured macrophages, adhered to the newly formed subventricular vascular plexus, and then divided into daughter cells. Eventually, these CD31+F4/80+ cells transdifferentiated into NG2/PDGFRß/desmin-expressing cerebrovascular pericytes, enwrapping and associating with vascular endothelial cells. These data indicate that a subset of cerebrovascular pericytes derive from mature macrophages in the very early phase of CNS vascular development, which in turn are recruited from sites of embryonic hematopoiesis such as the yolk sac by way of blood flow.

Effects of Kamishoyosan, a Traditional Japanese Kampo Medicine, on Pain Conditions in Patients with Intractable Persistent Dentoalveolar Pain Disorder.

There are patients who suffer from persistent dentoalveolar pain disorder (PDAP) which is a pain of the teeth, either dentoalveolar pain or nonodontogenic toothache, and its cause has not yet been identified. An effective intervention for PDAP has not yet been established. Interventions for patients with PDAP are generally pharmacological treatments such as antidepressants, anticonvulsants, and pregabalin. However, these medicines are not always effective for patients. The pain disorder in the orofacial region including temporomandibular disorder (TMD) and PDAP was effectively treated with our original exercise therapy. However, we did observe some intractable cases of PDAP even when our original exercise therapy was used. This paper presents our findings in which Kamishoyosan improved the pain intensity in 14 out of 15 PDAP patients refractory to our original exercise therapy.

Kynurenine causes vasodilation and hypotension induced by activation of KCNQ-encoded voltage-dependent K(+) channels.

Kynurenine is a potential contributor to hypotension in animal and human sepsis. The present study was designed to examine whether the voltage-dependent K(+) channels encoded by the KCNQ gene family (Kv7 channels) mediate vasodilator effects of kynurenine and whether modulation of these channels ameliorates hypotension caused by this compound. Rat aortas and mesenteric arteries or human omental arteries without endothelium were used. Some rings were incubated with the selective Kv7 channel inhibitor linopirdine (10 µM). l-Kynurenine (10 µM-1 mM) induced concentration-dependent relaxation in rat aortas and mesenteric arteries as well as human omental arteries, whereas linopirdine abolished the relaxation. l-Kynurenine (1 mM) produced hyperpolarization of vascular smooth muscle, which was reversed by linopirdine (10 µM). Wistar rats received l-kynurenine (1 mM) iv and subsequent linopirdine (10 µM) iv under 3% sevoflurane inhalation. l-Kynurenine iv caused hypotension, whereas linopirdine iv partially reversed it. In conclusion, kynurenine dilates arteries from rats as well as humans via Kv7 channels in the vascular smooth muscle. In rats, this tryptophan metabolite causes hypotension, which is partly counteracted by Kv7 channel inhibition. These results suggest that modulation of Kv7 channels may be a novel strategy to treat hypotension induced by the kynurenine.

Cerebral oxygenation in the beach chair position before and during general anesthesia in patients with and without cardiovascular risk factors.

STUDY OBJECTIVES: To evaluate changes in cerebral tissue oxygen index (TOI) values under the beach chair position before and during general anesthesia in surgical patients with or without cardiovascular risk factors. DESIGN: Prospective study. SETTING: Operating room in the university hospital. PATIENTS: Ninety-one patients undergoing surgery, including healthy patients (n = 28), patients with 1 cardiovascular risk factor (n = 33), and those with more than 1 risk factor (n = 30). INTERVENTIONS AND MEASUREMENTS: Cerebral TOI the day before and during general anesthesia was evaluated using a near-infrared spectroscopy NIRO-200 (Hamamatsu Photonics, Hamamatsu, Japan) for each patient. The initial TOI measurement in the supine position after a 10-minute rest or 10 minute after the endotracheal intubation was followed by measurements in 30° and subsequent 60° upright position for 5 minutes. Phenylephrine 0.1 mg and/or ephedrine 4 mg was administered intravenously to maintain mean blood pressure above 60 mm Hg accordingly. MAIN RESULTS: The beach chair position decreased mean arterial blood pressure and heart rate under general anesthesia, although patients with more than 1 cardiovascular risk factor needed significantly more phenylephrine doses to maintain mean blood pressure above 60 mm Hg. Values of TOI were within the normal range of about 70% before and during anesthesia in all groups. CONCLUSIONS: The beach chair position under general anesthesia did not alter cerebral oxygenation in patients with or without cardiovascular risk factors showing normal preoperative cerebral TOI values when the mean blood pressure was maintained above 60 mm Hg. The careful management using the cerebral oxygenation monitoring appears to maintain cerebral perfusion in the beach chair position during general anesthesia.

Propofol-induced relaxation of rat aorta is altered by aging.

BACKGROUND: Propofol causes vasodilation via endothelium-dependent and -independent mechanisms. Because endothelial function is impaired with aging, the effects of propofol on endothelium-dependent vasodilation might be altered by aging. The aim of this study was thus to determine the effects of aging on vascular responses to propofol. METHODS: Young (4-6 weeks old) or adult (16-25 weeks old) rats were anesthetized with sevoflurane. The thoracic aorta was dissected and cut into pieces 3-4 mm in length. In some rings, the endothelium was deliberately removed. The ring segment of the aorta was mounted for isometric force recording at a resting tension of 0.5-1.0 g in a 2 ml organ bath, containing Krebs-Ringer bicarbonate buffer. Arteries were precontracted with phenylephrine, and the function of endothelium was confirmed with acetylcholine. Then, we studied the concentration-dependent effects of propofol in endothelium-intact (control group) and -denuded aortic rings (denuded group), as well as those treated with N(ω)-nitro-L-arginine methylester (L-NAME group). RESULTS: Relaxation due to propofol was observed in the control groups of both young and adult rats in a concentration-dependent manner, but the magnitude of relaxation was significantly greater in young rats. In addition, in young rats, relaxation due to propofol was significantly and equally reduced in both L-NAME and denuded groups at all propofol concentrations that we studied (10(-6)-10(-3) M). In adult rats, relaxation due to propofol was quite similar between control and L-NAME groups at all propofol concentrations, whereas it was significantly reduced in the denuded group. CONCLUSION: These results suggest that endothelium-derived nitric oxide plays an important role in propofol-induced vasodilation in young rats, but not in adult rats.

Alert cell strategy: mechanisms of inflammatory response and organ protection.

Systemic inflammatory response syndrome (SIRS) is triggered by various factors such as surgical operation, trauma, burn injury, ischemia, pancreatitis and bacterial translocation. Sepsis is a SIRS associated with bacterial infection. SIRS and sepsis tend to trigger excessive production of inflammatory cytokines and other inflammatory molecules and induce multiple organ failure, such as acute lung injury, acute kidney injury and inflammatory cardiac injury. Epithelial and endothelial cells in some major organs express inflammatory receptors on the plasma membrane and work as alert cells for inflammation, and regulation of these alert cells could have a relieving effect on the inflammatory response. In inflammatory conditions, initial cardiac dysfunction is mediated by decreased preload and adequate infusion therapy is required. Tachyarrhythmia is a complication of inflammatory conditions and early control of the inflammatory reaction would prevent the structural remodeling that is resistant to therapies. Furthermore, there seems to be crosstalk between major organs with a central focus on the kidneys in inflammatory conditions. As an alert cell strategy, volatile anesthetics, sevoflurane and isoflurane, seem to have anti-inflammatory effects, and both experimental and clinical studies have shown the beneficial effects of these drugs in various settings of inflammatory conditions. On the other hand, in terms of intravenous anesthetics, propofol and ketamine, their current status is still controversial as there is a lack of confirmatory evidence on whether they have an organ-protective effect in inflammatory conditions. The local anesthetic lidocaine suppressed inflammatory responses upon both systemic and local administration. For the control of inflammatory conditions, anesthetic agents may be a target of drug development in accordance with other treatments and drugs.

The efficacy of a multidisciplinary group program for patients with refractory chronic pain.

BACKGROUND: Chronic pain is a major problem because it can result in not only a reduction in activities of daily living and quality of life but also requires initiation of social assistance. Seeking only to eliminate pain itself would appear to be too narrow an objective, in addition to often being unachievable; therefore, a multifaceted, comprehensive approach with multiple objectives is needed. OBJECTIVE: To describe the effects of a program (the 'Chronic Pain Class') offering cognitive behavioural therapy to small groups of individuals with refractory chronic pain in Japan. Exercise was an important feature of the program. METHODS: A total of 46 patients who were experiencing treatment difficulties and decreased activity participated in the program. The programs were conducted in groups of five to seven patients who met weekly for nine weeks. Weekly sessions, which were approximately 2 h in duration, combined lectures with exercise. Several measures related to pain and physical function were administered at the beginning and the conclusion of the program. RESULTS: Nine patients dropped out during the program. A number of measures (eg, pain intensity, disability, catastrophizing thoughts) showed significant improvements after intervention (P<0.002 after Bonferroni correction). Furthermore, most measures of physical function showed substantial improvement, especially seated forward bends, zig-zag walking, self-care and 6 min walk test (P<0.001). CONCLUSION: The results of the present study provide evidence that a combination of cognitive behavioural therapy and exercise should be recommended to patients with refractory chronic pain.

Intravenous lidocaine and magnesium for management of intractable trigeminal neuralgia: a case series of nine patients.

Most patients suffering from trigeminal neuralgia (TN) benefit from medical therapy, for example carbamazepin, gabapentin, and pregabalin, individually or in combination. Nonetheless, some patients experience severe and intractable pain despite such medication, or the medication eliminates their pain but they experience intolerable side effects sufficient to warrant discontinuation. Intravenous magnesium and lidocaine have been used for management of intractable neuropathic pain. We treated nine patients with TN by using an intravenous infusion of a combination of 1.2 g magnesium and 100 mg lidocaine for 1 hour, once a week for 3 weeks. All patients experienced sound pain relief after the combined intravenous infusion therapy. Two patients experienced short and mild dizziness after the therapy, but no severe side effects were reported.

The supine-to-prone position change induces modification of endotracheal tube cuff pressure accompanied by tube displacement.

STUDY OBJECTIVES: To determine whether the supine-to-prone position change displaced the endotracheal tube (ETT) and, if so, whether the displacement related to this change modified ETT cuff pressure. DESIGN: Prospective study. SETTING: Operating room of a university hospital. PATIENTS: 132 intubated, adult, ASA physical status 1, 2, and 3 patients undergoing lumbar spine surgery. INTERVENTIONS AND MEASUREMENTS: After induction of anesthesia, each patient's trachea was intubated. The insertion depth of each ETT was 23 cm for men and 21 cm for women at the upper incisors. In the supine position and after the supine-to-prone position change with the head rotated to the right, the length from the carina to ETT tip and ETT cuff pressure were measured. MAIN RESULTS: After the supine-to-prone position change, 91.7% patients had ETT tube displacement. Of these, 48% of patients' ETT moved ≥ 10 mm, whereas 86.3% of patients had changes in tube cuff pressure. There was a slight but significant correlation between ETT movement and change in cuff pressure. Depending on the position change, ETT cuff pressure decreased and the ETT tended to withdraw. CONCLUSIONS: After the supine-to-prone position change, patients had ETT tube displacement. Such ETT movement may be accompanied by a decrease in cuff pressure.

Isoflurane pretreatment preserves adenosine triphosphate-sensitive K(+) channel function in the human artery exposed to oxidative stress caused by high glucose levels.

BACKGROUND: Adenosine triphosphate (ATP)-sensitive K(+) channels contribute to significant regulatory mechanisms related to organ blood flow in both physiological and pathological conditions. High glucose impairs arterial ATP-sensitive K(+) channel activity via superoxide production. However, the effects of anesthetics on this pathological process have not been evaluated in humans. In the present study, we investigated whether pretreatment with the volatile anesthetic isoflurane preserves ATP-sensitive K(+) channel activity in the human artery exposed to oxidative stress caused by high glucose. METHODS: All experiments were performed using human omental arteries without endothelium in the presence of d-glucose (5.5 mmol/L). Some arteries were treated with isoflurane (1.15% or 2.3%) in combination with d- or l-glucose (20 mmol/L) for 60 minutes, and then only isoflurane was discontinued. Relaxation and hyperpolarization of arterial segments in response to an ATP-sensitive K(+) channel opener levcromakalim were evaluated using the isometric force recording or electrophysiological study, respectively. Superoxide production was determined by dihydroethidium fluorescence. Immunohistochemical analysis for a subunit of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p47phox was performed. Data were evaluated using repeated-measures analysis of variance or a factorial analysis of variance as appropriate, followed by Scheffé test. RESULTS: The ATP-sensitive K(+) channel antagonist glibenclamide (10(-6) mol/L) abolished relaxation induced by cumulative addition of levcromakalim (10(-8) to 10(-5) mol/L) in arteries treated with l-glucose (20 mmol/L). Incubation with d-glucose (20 mmol/L) impaired the vasorelaxation induced by levcromakalim. The selective NADPH oxidase NOX2 inhibitor gp91ds-tat (10(-6) mol/L) and pretreatment with isoflurane (1.15% and 2.3%) restored relaxation in response to levcromakalim in arteries treated with d-glucose (20 mmol/L). Isoflurane (2.3%), gp91ds-tat (10(-6) mol/L), and their combination similarly restored hyperpolarization in response to levcromakalim (3 × 10(-6) mol/L) in arteries treated with d-glucose (20 mmol/L). Along with these results, isoflurane (2.3%) reduced superoxide production and the intracellular mobilization of the cytosolic NOX2 subunit p47phox toward smooth muscle cell membrane in arteries treated with d-glucose (20 mmol/L). CONCLUSIONS: We have demonstrated for the first time a beneficial effect from the pretreatment with isoflurane on the isolated human artery. Pretreatment with isoflurane preserves ATP-sensitive K(+) channel activity in the human omental artery exposed to oxidative stress induced by high glucose, whereas the effect seems to be mediated by NADPH oxidase inhibition. Volatile anesthetics may protect human visceral arteries from malfunction caused by oxidative stress.

Role of ion channels in sepsis-induced atrial tachyarrhythmias in guinea pigs.

BACKGROUND AND PURPOSE: Supraventricular tachyarrhythmias, including atrial fibrillation, are occasionally observed in patients suffering from sepsis. Modulation of cardiac ion channel function and expression by sepsis may have a role in the genesis of tachyarrhythmias. EXPERIMENTAL APPROACH: Sepsis was induced by LPS (i.p.; 300 µg·kg(-1) ) in guinea pigs. Membrane potentials and ionic currents were measured in atrial myocytes isolated from guinea pigs 10 h after LPS, using whole cell patch-clamp methods. KEY RESULTS: In atrial cells from LPS-treated animals, action potential duration (APD) was significantly shortened. It was associated with a reduced L-type Ca(2+) current and an increased delayed rectifier K(+) current. These electrophysiological changes were eliminated when N(G) -nitro-l-arginine methyl ester (l-NAME) or S-ethylisothiourea was given together with LPS. In atrial tissues from LPS-treated animals, Ca(2+) channel subunits (Ca(v) 1.2 and Ca(v) 1.3) decreased and delayed rectifier K(+) channel subunits (K(v) 11.1 and K(v) 7.1) increased. However, L-NAME treatment did not substantially reverse such changes in atrial expression in LPS-treated animals, with the exception that K(v) 11.1 subunits returned to control levels. After LPS injection, inducible NOS in atrial tissues was up-regulated, and atrial NO production clearly increased. CONCLUSIONS AND IMPLICATIONS: In atrial myocytes from guinea pigs with sepsis, APD was significantly shortened. This may reflect nitration of the ion channels which would alter channel functions, rather than changes in atrial expression of the channels. Shortening of APD could serve as one of the mechanisms underlying atrial tachyarrhythmia in sepsis.

Redefinition of the pelvic connective tissue: in situ histologic examination.

OBJECTIVES: : The objectives of this study were to find a common perspective in clinical and gross/systemic anatomy for the pelvic connective tissue (subperitoneal fascia) and to establish a new pelvic anatomy. METHODS: : The histologic sections from 5 fixed cadavers were obtained from a total of 17 fixed and 11 fresh cadavers. On the basis of our past surgical and research findings, the relationship between the pelvic organs and the pelvic connective tissue was observed from in situ histologic sections of the whole pelvis. RESULTS: : Subperitoneal fasciae, a term that is expressed in gross/systemic anatomy, were manifested as a 3-dimensional structure by a complex of "ligaments," as defined in clinical terminology. In the supine position, this structure consisted of the sagittal plane formed by the rectouterine ligament and vesicouterine ligament; the perpendicular plane by the vesicohypogastric fascia, transverse cervical ligament, and lateral rectal ligament; and the horizontal plane by the superior fascia of the levator ani muscle. CONCLUSIONS: : The ligaments were regarded as a compatible component of the subperitoneal fascia. Our anatomical concept of the pelvic connective tissue differed from that for classic clinical anatomy.

Effects of gabapentin on brain hyperactivity related to pain and sleep disturbance under a neuropathic pain-like state using fMRI and brain wave analysis.

Neuropathic pain is the most difficult pain to manage in the pain clinic, and sleep problems are common among patients with chronic pain including neuropathic pain. In the present study, we tried to visualize the intensity of pain by assessing neuronal activity and investigated sleep disturbance under a neuropathic pain-like state in mice using functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG)/electromyogram (EMG), respectively. Furthermore, we investigated the effect of gabapentin (GBP) on these phenomena. In a model of neuropathic pain, sciatic nerve ligation caused a marked decrease in the latency of paw withdrawal in response to a thermal stimulus only on the ipsilateral side. Under this condition, fMRI showed that sciatic nerve ligation produced a significant increase in the blood oxygenation level-dependent (BOLD) signal intensity in the pain matrix, which was significantly decreased 2 h after the i.p. injection of GBP. Based on the results of an EEG/EMG analysis, sciatic nerve-ligated animals showed a statistically significant increase in wakefulness and a decrease in non-rapid eye movement (NREM) sleep during the light phase, and the sleep disturbance was almost completely alleviated by a higher dose of GBP in nerve-ligated mice. These findings suggest that neuropathic pain associated with sleep disturbance can be objectively assessed by fMRI and EEG/EMG analysis in animal models. Furthermore, GBP may improve the quality of sleep as well as control pain in patients with neuropathic pain.

The modulation of vascular ATP-sensitive K+ channel function via the phosphatidylinositol 3-kinase-Akt pathway activated by phenylephrine.

The present study examined the modulator role of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway activated by the alpha-1 adrenoceptor agonist phenylephrine in ATP-sensitive K(+) channel function in intact vascular smooth muscle. We evaluated the ATP-sensitive K(+) channel function and the activity of the PI3K-Akt pathway in the rat thoracic aorta without endothelium. The PI3K inhibitor 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002) (10(-5) M) augmented relaxation in response to the ATP-sensitive K(+) channel opener levcromakalim (10(-8) to 3 x 10(-6) M) in aortic rings contracted with phenylephrine (3 x 10(-7) M) but not with 9,11-dideoxy-11alpha,9alpha-epoxy-methanoprostaglandin F(2alpha) (U46619; 3 x 10(-8) M), although those agents induced similar contraction. ATP-sensitive K(+) channel currents induced by levcromakalim (10(-6) M) in the presence of phenylephrine (3 x 10(-7) M) were enhanced by the nonselective alpha-adrenoceptor antagonist phentolamine (10(-7) M) and LY294002 (10(-5) M). Levels of the regulatory subunits of PI3K p85-alpha and p55-gamma increased in the membrane fraction from aortas without endothelium treated with phenylephrine (3 x 10(-7) M) but not with U46619 (3 x 10(-8) M). Phenylephrine simultaneously augmented Akt phosphorylation at Ser473 and Thr308. Therefore, activation of the PI3K-Akt pathway seems to play a role in the impairment of ATP-sensitive K(+) channel function in vascular smooth muscle exposed to alpha-1 adrenergic stimuli.