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Responses to a sensory stimulus are inhibited by a preceding stimulus; if the two stimuli are identical, paired-pulse suppression (PPS) occurs; if the preceding stimulus is too weak to reliably elicit the target response, prepulse inhibition (PPI) occurs. PPS and PPI represent excitability changes in neural circuits induced by the first stimulus, but involve different mechanisms and are impaired in different diseases, e.g., impaired PPS in schizophrenia and Alzheimer’s disease and impaired PPI in schizophrenia and movement disorders. Therefore, these measures provide information on several inhibitory mechanisms that may have roles in clinical conditions. In the present study, PPS and PPI of the auditory change-related cortical response were examined to establish normative data on healthy subjects (35 females and 32 males, aged 19–70 years). We also investigated the effects of age and sex on PPS and PPI to clarify whether these variables need to be considered as biases. The test response was elicited by an abrupt increase in sound pressure in a continuous sound and was recorded by electroencephalography. In the PPS experiment, the two change stimuli to elicit the cortical response were a 15-dB increase from the background of 65 dB separated by 600 ms. In the PPI experiment, the prepulse and test stimuli were 2- and 10-dB increases, respectively, with an interval of 50 ms. The results obtained showed that sex exerted similar effects on the two measures, with females having stronger test responses and weaker inhibition. On the other hand, age exerted different effects: aging correlated with stronger test responses and weaker inhibition in the PPS experiment, but had no effects in the PPI experiment. The present results suggest age and sex biases in addition to normative data on PPS and PPI of auditory change-related potentials. PPS and PPI, as well as other similar paradigms, such as P50 gating, may have different and common mechanisms. Collectively, they may provide insights into the pathophysiologies of diseases with impaired inhibitory function.

Abstract Introduction Central neuropathic pain (CNeP) is difficult to treat and has diverse etiology, including spinal cord injury (CNePSCI), Parkinson’s disease (CNePPD), and central post-stroke pain (CPSP). The safety and efficacy of mirogabalin have been demonstrated in short-term trials, including patients with CNePSCI. The objective of our study was to confirm the safety/efficacy of mirogabalin in patients with CNePPD and CPSP, and obtain long-term data for CNePSCI. Methods This 52-week, open-label extension of a previous randomized controlled study was conducted across Japan, Korea, and Taiwan. Patients with CNePSCI, CNePPD, or CPSP received twice daily (BID) 5–10 mg mirogabalin for a 4-week titration period, after which the dosage was maintained for 47 weeks at a maximum of 15 mg BID, followed by a 1-week taper period receiving the same dose but only administered once daily. The primary endpoint was safety, assessed primarily by incidence and severity of treatment-emergent adverse events (TEAEs). Efficacy was assessed in a post hoc analysis of data obtained by the short-form McGill Pain Questionnaire (SF-MPQ). Results Of the 210 patients enrolled, 106, 94, and 10 had CNePSCI, CPSP, and CNePPD, respectively. The mean overall age of patients was 62.9 years, and most patients were male and of Japanese ethnicity. TEAEs occurred in 84.8% of patients, the most common being somnolence (16.7%), peripheral edema (12.4%), edema (11.4%), nasopharyngitis (11.0%), and dizziness (7.6%). Most TEAEs were mild. Severe and serious TEAEs occurred in 6.2% and 13.3% of patients, respectively. All patient groups experienced reductions in SF-MPQ visual analog scores for pain: mean ± standard deviation changes from baseline at week 52 were −2.3 ± 21.13 mm (CNePSCI), −17.0 ± 24.99 mm (CPSP), and −17.1 ± 35.32 mm (CNePPD). Conclusion Mirogabalin was generally safe, well tolerated, and effective for treatment of CNeP in this long-term study. Trial registration ClinicalTrials.gov identifier, NCT03901352.

The 40-Hz auditory steady-state response (ASSR) has received special attention as an index of gamma oscillations owing to its association with various neuropsychiatric disorders including schizophrenia. When a periodic stimulus is presented, oscillatory responses are often elicited not only at the stimulus frequency, but also at its harmonic frequencies. However, little is known about the effect of 40-Hz subharmonic stimuli on the activity of the 40-Hz ASSR. In the present magnetoencephalography study, we focused on the nature of oscillation harmonics and examined oscillations in a wide frequency range using a time-frequency analysis during the 6.67-, 8-, 10-, 13.3-, 20-, and 40-Hz auditory stimuli in 23 healthy subjects. The results suggested that the 40-Hz ASSR represents activation of a specific circuit tuned to this frequency. Particularly, oscillations elicited by 13.3- and 20-Hz stimuli exhibited significant enhancement at 40 Hz without changing those at the stimulus frequency. In addition, it was found that there was a non-linear response to stimulation in the beta band. We also demonstrated that the inhibition of beta to low-gamma oscillations by the 40-Hz circuit contributed to the violation of the rule that harmonic oscillations gradually decrease at higher frequencies. These findings can advance our understanding of oscillatory abnormalities in patients with schizophrenia in the future.

Wind-up like pain or temporal summation of pain is a phenomenon in which pain sensation is increased in a frequency-dependent manner by applying repeated noxious stimuli of uniform intensity. Temporal summation in humans has been studied by observing the increase in pain or flexion reflex by repetitive electrical or thermal stimulations. Nonetheless, because the measurement is accompanied by severe pain, a minimally invasive method is desirable. Gradual augmentation of flexion reflex and pain induced by repetitive stimulation of the sural nerve was observed using three stimulation methods—namely, bipolar electrical, magnetic, and monopolar electrical stimulation, with 11 healthy male subjects in each group. The effects of frequency, intensity, and number of repetitive stimuli on the increase in the magnitude of flexion reflex and pain rating were compared among the three methods. The reflex was measured using electromyography (EMG) from the short head of the biceps femoris. All three methods produced a frequency- and intensity-dependent progressive increase in reflex and pain; pain scores were significantly lower for magnetic and monopolar stimulations than for bipolar stimulation (P < 0.05). The slope of increase in the reflex was steep during the first 4–6 stimuli but became gentler thereafter. In the initial phase, an increase in the reflex during the time before signals of C-fibers arrived at the spinal cord was observed in experiments using high-frequency stimulation, suggesting that wind-up was caused by inputs of A-fibers without the involvement of C-fibers. Magnetic and monopolar stimulations are minimally invasive and useful methods for observing the wind-up of the flexion reflex in humans. Monopolar stimulation is convenient because it does not require special equipment. There is at least a partial mechanism underlying the wind-up of the flexion reflex that does not require C-fibers.

Previous studies have suggested that change-related cortical responses are phenomena similar to the onset response and could be applied to the loudness dependence of auditory evoked potential (LDAEP) paradigm. In the present study, we examined the relationship between LDAEP and the change-related response using electroencephalography findings in 50 healthy subjects. There were five conditions (55, 65, 75, 85, and 95 dB) for LDAEP and five similar conditions (abrupt sound pressure increase from 70 to 75, 80, 85, 90, and 95 dB) for the change-related response. Both the onset and abrupt sound pressure increase evoked a triphasic response with peaks at approximately 50 (P50), 100 (N100), and 200 (P200) ms. We calculated the peak-to-peak amplitudes for P50/N100 and N100/P200. Medians and slopes for P50/N100 and N100/P200 amplitudes were calculated and compared between the two measures. Results revealed a significant correlation for both the slope and median for P50/N100 (r = 0.36, 0.37, p = 1.0 × 10-2, 7.9 × 10-3), N100/P200 (r = 0.40, 0.34, p = 4.0 × 10-3, 1.6 × 10-2), and P50/N100/P200 (r = 0.36, 0.35, p = 1.0 × 10-2, 1.3 × 10-2). These results suggested that the change-related response and LDAEP shared generation mechanisms at least partially.

Abstract Introduction Complexins (CPLXs), initially identified in neuronal presynaptic terminals, are cytoplasmic proteins that interact with the soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors (SNARE) complex to regulate the fusion of vesicles to the plasma membrane. Although much is known about CPLX function in neuronal synaptic vesicle exocytosis, their distribution and role in immune cells are still unclear. In this study, we investigated CPLX2 knockout (KO) mice to reveal the role of CPLXs in exocytosis of lymphocytes. Methods We examined the expression of CPLXs and SNAREs in lymphocytes. To study the effect of CPLXs on the immune system in vivo, we analyzed the immune phenotype of CPLX2 KO mice. Furthermore, antibodies secretion from the peritoneal cavity, spleen, and bone marrow cells of wild‐type (WT) and CPLX2 KO mice were determined. Results CPLX2 was detected in B cells but not in T cells, while other CPLXs and SNAREs were expressed at a similar level in both B and T cells. To clarify the function of CPLX2 in B lymphocytes, serum concentrations of immunoglobulin G (IgG), IgA, IgM, and IgE were measured in WT and CPLX2 KO mice using enzyme‐linked immunosorbent assay. The level of IgM, which mainly consists of natural antibodies, was higher in KO mice than that in WT mice, while the levels of other antibodies were similar in both types of mice. Additionally, we found that spontaneous secretion of IgM and IgG1 was enhanced from the splenic antibody‐secreting cells (ASCs) of CPLX2 KO mice. Conclusion Our data suggest that CPLX2 inhibits spontaneous secretion of IgM and IgG1 from splenic ASCs. This study provides new insight into the mechanism of antibody secretion of ASCs.

Abstract Introduction Picky eating appears to be associated with poor health outcomes and thus it might have a role in musculoskeletal pain in adults. However, this relationship has not been investigated yet. The aim of the present study was to determine whether the number of musculoskeletal pain regions was associated with picky eating, which was characterized by food intake balance of familiar products or self-identification. Methods A total of 4660 adult subjects were enrolled in this study. Picky eating was assessed in two ways; a countable score and self-identification of picky eating. For the countable score, the number of food items, which the subjects usually did not consume among a list of 11 familiar products was measured. Self-identification as a picky eater was defined through a single question. The presence of musculoskeletal pain; in the neck, low back, knee, back, or arm, within 2 months of the survey was also identified. Results Of all subjects, 2654 (56%) had musculoskeletal pain in at least one region. The prevalence of musculoskeletal pain in every region was seen as consistently higher in subjects who self-identified as picky eaters than those who were non-picky eaters. In multiple linear regression analysis, the number of pain regions was significantly associated with older age, females, self-identification as a picky eater, and low body weight, not but the countable score. Conclusions There may be an association between musculoskeletal pain and negative beliefs about one’s own eating behaviors.

Sensory processing is disrupted in several psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorder. In this review, we focus on the electrophysiological auditory steady-state response (ASSR) driven by high-frequency stimulus trains as an index for disease-associated sensory processing deficits. The ASSR amplitude is suppressed within the gamma band (≥30 Hz) among these patients, suggesting an imbalance between GABAergic and N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission. The reduced power and synchronization of the 40-Hz ASSR are robust in patients with schizophrenia. In recent years, similar ASSR deficits at gamma frequencies have also been reported in patients with bipolar disorder and autism spectrum disorder. We summarize ASSR abnormalities in each of these psychiatric disorders and suggest that the observed commonalities reflect shared pathophysiological mechanisms. We reviewed studies on phase resetting in which a salient sensory stimulus affects ASSR. Phase resetting induces the reduction of both the amplitude and phase of ASSR. Moreover, phase resetting is also affected by rare auditory stimulus patterns or superimposed stimuli of other modalities. Thus, sensory memory and multisensory integration can be investigated using phase resetting of ASSR. Here, we propose that ASSR amplitude, phase, and resetting responses are sensitive indices for investigating sensory processing dysfunction in psychiatric disorders.

PurposeThe purpose of the present study was to investigate the visual attentional behavior towards a pain-affected area and face/body images using eye tracking in complex regional pain syndrome (CRPS) patients. Moreover, we investigated the relationship between visual attentional behavior and clinical symptoms.Patients and methodsEight female patients with CRPS type 1 in their upper limbs and 8 healthy adult women participated in this study. First, the participants were asked to watch videoclips in a relaxed manner (Videoclip 1 featured young adults who introduced themselves; Videoclip 2 featured young adults touching the hand of the other person sitting across from them with their hand.) Eye movement data were tracked with eye-tracking glasses.ResultsIn video clip 1, the fixation duration (FD) and fixation count (FC) on faces tended to be lower in CRPS patients than in healthy controls. This tendency was found in patients with low body cognitive distortions. In video clip 2, CRPS patients displayed significantly lower FD and FC on the unaffected hand while watching a video of the unaffected hand being touched compared with healthy controls. Moreover, patients with low body cognitive distortion displayed significantly longer FD on the affected hand.ConclusionSome CRPS patients differed in visual attentional behavior toward the face and body compared with healthy controls. In addition, our findings suggest that patients with lower body cognitive distortion may have a high visual attention for the affected hand, while patients with higher distortion may be neglecting the affected hand.

Introduction: Facial expression to pain is an important pain indicator; however, facial movements look unresponsive when perceiving mild pain. The present study investigates whether pain magnitude modulates the relationship between subjective pain rating and an observer evaluation of facial expression. Methods: Twelve healthy volunteers were recruited to obtain 108 samples for pain rating with Visual Analogue Scale (VAS). Subjects underwent three different mechanical painful stimuli (monofilament forces of 100 g, 300 g, and 600 g) over three sessions and their facial expressions were videotaped throughout all sessions. Three observers independently evaluated facial expression of the subjects with a four-point categorical scale (no pain, mild pain, moderate pain, and severe pain). The correlations between subjective pain ratings and the evaluation of facial expression were analyzed in dichotomous group which was low pain ratings (VAS

In the sensory cortex, cross-modal interaction occurs during the early cortical stages of processing; however, its effect on the speed of neuronal activity remains unclear. In this study, we used magnetoencephalography (MEG) to investigate whether tactile stimulation influences auditory steady-state responses (ASSRs). To this end, a 0.5-ms electrical pulse was randomly presented to the dorsum of the left or right hand of 12 healthy volunteers at 700 ms while a train of 25-ms pure tones were applied to the left or right side at 75 dB for 1,200 ms. Peak latencies of 40-Hz ASSR were measured. Our results indicated that tactile stimulation significantly shortened subsequent ASSR latency. This cross-modal effect was observed from approximately 50 ms to 125 ms after the onset of tactile stimulation. The somatosensory information that appeared to converge on the auditory system may have arisen during the early processing stages, with the reduced ASSR latency indicating that a new sensory event from the cross-modal inputs served to increase the speed of ongoing sensory processing. Collectively, our findings indicate that ASSR latency changes are a sensitive index of accelerated processing.

Rapid detection of sensory changes is important for survival. We have previously used change-related cortical responses to study the change detection system and found that the generation of a change-related response was based on sensory memory and comparison processes. However, it remains unclear whether change-related cortical responses reflect processing speed. In the present study, we simultaneously recorded the auditory steady-state response (ASSR) and change-related response using magnetoencephalography to investigate the acceleration effects of sensory change events. Overall, 13 healthy human subjects (four females and nine males) completed an oddball paradigm with a sudden change in sound pressure used as the test stimulus, i.e., the control stimulus was a train of 25-ms pure tones at 75 dB for 1,200 ms, whereas the 29th sound at 700 ms of the test stimulus was replaced with a 90-dB tone. Thereafter, we compared the latency of ASSR among four probabilities of test stimulus (0, 25, 75, and 100%). For both the control and test stimulus, stronger effects of acceleration on ASSR were observed when the stimulus was rarer. This finding indicates that ASSR and change-related cortical response depend on physical changes as well as sensory memory and comparison processes. ASSR was modulated without changes in peripheral inputs, and brain areas higher than the primary cortex could be involved in exerting acceleration effects. Furthermore, the reduced latency of ASSR clearly indicated that a new sensory event increased the speed of ongoing sensory processing. Therefore, changes in the latency of ASSR are a sensitive index of accelerated processing.

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.

Despite their essential roles in signal processing in the brain, the functions of interneurons currently remain unclear in humans. We recently developed a method using the prepulse inhibition of sensory evoked cortical responses for functional measurements of interneurons. When a sensory feature is abruptly changed in a continuous sensory stimulus, change-related cortical responses are recorded using MEG. By inserting a weak change stimulus (prepulse) before the test change stimulus, it is possible to observe the inhibition of the test response. By manipulating the prepulse-test interval (PTI), several peaks appear in inhibition, suggesting the existence of temporally distinct mechanisms. We herein attempted to separate these components through the oral administration of diazepam and baclofen. The test stimulus and prepulse were an abrupt increase in sound pressure in a continuous click train of 10 and 5 dB, respectively. The results obtained showed that the inhibition at PTIs of 10 and 20 ms was significantly greater with diazepam than with the placebo administration, suggesting increased GABAA-mediated inhibition. Baclofen decreased inhibition at PTIs of 40 and 50 ms, which may have been due to the activation of GABAB autoreceptors. Therefore, the present study separated at least two inhibitory mechanisms pharmacologically.

Sensory suppression is a mechanism that attenuates selective information. As for long-latency suppression in auditory and somatosensory systems, paired-pulse suppression, observed as 2 identical stimuli spaced by approximately 500 ms, is widely known, though its mechanism remains to be elucidated. In the present study, we investigated the relationship between auditory and somatosensory long-latency suppression of change-related cortical responses using magnetoencephalography. Somatosensory change-related responses were evoked by an abrupt increase in stimulus strength in a train of current-constant square wave pulses at 100 Hz to the left median nerve at the wrist. Furthermore, auditory change-related responses were elicited by an increase in sound pressure by 15 dB in a continuous sound composed of a train of 25-ms pure tones. Binaural stimulation was used in Experiment 1, while monaural stimulation was used in Experiment 2. For both somatosensory and auditory stimuli, the conditioning and test stimuli were identical, and inserted at 2400 and 3000 ms, respectively. The results showed clear suppression of the test response in the bilateral parisylvian region, but not in the postcentral gyrus of the contralateral hemisphere in the somatosensory system. Similarly, the test response in the bilateral supratemporal plane (N100m) was suppressed in the auditory system. Furthermore, there was a significant correlation between suppression of right N100m and right parisylvian activity, suggesting that similar mechanisms are involved in both. Finally, a high test-retest reliability for suppression was seen with both modalities. Suppression revealed in the present study is considered to reflect sensory inhibition ability in individual subjects.

Blood stasis is a very important pathophysiological concept not only in Kampo but also in traditional Chinese medicine. Blood stasis indicates severe disease. Fuku shin (the abdominal exam) and Zetsu shin (the tongue exam) are the most important approaches of the 4 diagnostic procedures in Kampo . Tenderness of the lower abdominal region ( Sho fuku koh man ) and distended sublingual veins have been mentioned as typical signs of blood stasis in Kampo or traditional Chinese medicine. The aim of the present study was to determine the association between Sho fuku koh man and distended sublingual veins. An appearance of sublingual veins and a level of Sho fuku koh man showed a significant and positive correlation ( r s = .5248; n = 279; P < .0001). In conclusion, the relationship between the appearance of sublingual veins and the level of Sho fuku koh man showed a significant and positive correlation.

The auditory steady-state response (ASSR) elicited by a periodic sound stimulus is a neural oscillation recorded by magnetoencephalography (MEG), which is phase-locked to the repeated sound stimuli. This ASSR phase alternates after an abrupt change in the feature of a periodic sound stimulus and returns to its steady-state value. An abrupt change also elicits a MEG component peaking at approximately 100−180 ms (called “Change-N1m”). We investigated whether both the ASSR phase deviation and Change-N1m were affected by the magnitude of change in sound pressure. The ASSR and Change-N1m to 40 Hz click-trains (1000 ms duration, 70 dB), with and without an abrupt change (± 5, ± 10, or ± 15 dB) were recorded in ten healthy subjects. We used the source strength waveforms obtained by a two-dipole model for measurement of the ASSR phase deviation and Change-N1m values (peak amplitude and latency). As the magnitude of change increased, Change-N1m increased in amplitude and decreased in latency. Similarly, ASSR phase deviation depended on the magnitude of sound-pressure change. Thus, we suspect that both Change-N1m and the ASSR phase deviation reflect the sensitivity of the brain’s neural change-detection system.

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.

Sensory gating is a mechanism of sensory processing used to prevent an overflow of irrelevant information, with some indexes, such as prepulse inhibition (PPI) and P50 suppression, often utilized for its evaluation. In addition, those are clinically important for diseases such as schizophrenia. In the present study, we investigated long-latency paired-pulse suppression of change-related cortical responses using magnetoencephalography. The test change-related response was evoked by an abrupt increase in sound pressure by 15 dB in a continuous sound composed of a train of 25-ms pure tones at 65 dB. By inserting a leading change stimulus (prepulse), we observed suppression of the test response. In Experiment 1, we examined the effects of conditioning-test intervals (CTI) using a 25-ms pure tone at 80 dB as both the test and prepulse. Our results showed clear suppression of the test response peaking at a CTI of 600 ms, while maximum inhibition was approximately 30%. In Experiment 2, the effects of sound pressure on prepulse were examined by inserting prepulses 600 ms prior to the test stimulus. We found that a paired-pulse suppression greater than 25% was obtained by prepulses larger than 77 dB, i.e., 12 dB louder than the background, suggesting that long latency suppression requires a relatively strong prepulse to obtain adequate suppression, different than short-latency paired-pulse suppression reported in previous studies. In Experiment 3, we confirmed similar levels of suppression using electroencephalography. These results suggested that two identical change stimuli spaced by 600 ms were appropriate for observing the long-latency inhibition. The present method requires only a short inspection time and is non-invasive.

Background. Two prophylactic papillomavirus (HPV) vaccines have been available for primary prevention of cervical cancer. Although serious adverse effects (AE) were rare, more than 230 women have been suffering from severe AEs such as persistent pain and headache in Japan. Our research group started to treat adolescent females suffering from the AEs. Objective. To survey the characteristics of and the effects of cognitive behavioral therapy on adolescent female suffering from the AEs in Japanese multidisciplinary pain centers. Methods. One hundred and forty-five patients suffering from the AEs were reviewed retrospectively and 105 patients of them were provided guidance on home exercise and activities of daily living based partially on a cognitive-behavioral approach. The intensity of pain was rated by the patients using a numerical rating scale (NRS). Furthermore, the Hospital Anxiety and Depression Scale (HADS) and the Pain Catastrophizing Scale (PCS) were used. Results. Eighty out of the 105 patients who received the guidance were followed up, 10 displayed a marked improvement, and 43 showed some improvement. Conclusions. Guidance on home exercise and activities of daily living based on a cognitive-behavioral approach alleviated the AEs that women suffered from after HPV vaccination in Japan.

Despite their indispensable roles in sensory processing, little is known about inhibitory interneurons in humans. Inhibitory postsynaptic potentials cannot be recorded non-invasively, at least in a pure form, in humans. We herein sought to clarify whether prepulse inhibition (PPI) in the auditory cortex reflected inhibition via interneurons using magnetoencephalography. An abrupt increase in sound pressure by 10 dB in a continuous sound was used to evoke the test response, and PPI was observed by inserting a weak (5 dB increase for 1 ms) prepulse. The time course of the inhibition evaluated by prepulses presented at 10-800 ms before the test stimulus showed at least two temporally distinct inhibitions peaking at approximately 20-60 and 600 ms that presumably reflected IPSPs by fast spiking, parvalbumin-positive cells and somatostatin-positive, Martinotti cells, respectively. In another experiment, we confirmed that the degree of the inhibition depended on the strength of the prepulse, but not on the amplitude of the prepulse-evoked cortical response, indicating that the prepulse-evoked excitatory response and prepulse-evoked inhibition reflected activation in two different pathways. Although many diseases such as schizophrenia may involve deficits in the inhibitory system, we do not have appropriate methods to evaluate them; therefore, the easy and non-invasive method described herein may be clinically useful.

Objective: Frozen shoulder is a common disorder in general orthopedic practice, characterized by spontaneous onset of pain in the shoulder and accompanied by limitation of glenohumeral movement. Treatments for frozen shoulder include shoulder exercise, manual therapy, corticosteroid injection, manipulation under anesthesia, and arthroscopic capsular release. Several patients suffer from some degree of pain and range of motion limitation for up to 10 years even when these treatments are applied. Kampo , a traditional Japanese herbal medicine based on traditional Chinese herbal medicine, has been used for the treatment of pain in Japan. Nijutsuto has been a Kampo formula used to effectively treat frozen shoulder. Methods: Thirteen patients suffering from long-term frozen shoulder refractory to Western medical treatment were administered Nijututo . Results: Almost all patients experienced sound pain relief after Nijutsuto admnistration. There were no severe side effects reported. Conclusion: Nijutsuto combined with an exercise program improved pain intensity in 13 patients with long-term frozen shoulder.

Chronic pain is recognized as a public health problem that affects the general population physically, psychologically, and socially. However, there is little knowledge about the associated factors of chronic pain, such as the influence of weather, family structure, daily exercise, and work status.This survey had three aims: 1) to estimate the prevalence of chronic pain in Japan, 2) to analyze these associated factors, and 3) to evaluate the social burden due to chronic pain.We conducted a cross-sectional postal survey in a sample of 6000 adults aged ≥20 years. The response rate was 43.8%.The mean age of the respondents was 57.7 years (range 20-99 years); 39.3% met the criteria for chronic pain (lasting ≥3 months). Approximately a quarter of the respondents reported that their chronic pain was adversely influenced by bad weather and also oncoming bad weather. Risk factors for chronic pain, as determined by a logistic regression model, included being an older female, being unemployed, living alone, and no daily exercise. Individuals with chronic pain showed significantly lower quality of life and significantly higher psychological distress scores than those without chronic pain. The mean annual duration of absence from work of working-age respondents was 9.6 days (range 1-365 days).Our findings revealed that high prevalence and severity of chronic pain, associated factors, and significant impact on quality of life in the adult Japanese population. A detailed understanding of factors associated with chronic pain is essential for establishing a management strategy for primary care.

Previous studies showed that the amplitude and latency of the auditory offset cortical response depended on the history of the sound, which implicated the involvement of echoic memory in shaping a response. When a brief sound was repeated, the latency of the offset response depended precisely on the frequency of the repeat, indicating that the brain recognized the timing of the offset by using information on the repeat frequency stored in memory. In the present study, we investigated the temporal resolution of sensory storage by measuring auditory offset responses with magnetoencephalography (MEG). The offset of a train of clicks for 1 s elicited a clear magnetic response at approximately 60 ms (Off-P50m). The latency of Off-P50m depended on the inter-stimulus interval (ISI) of the click train, which was the longest at 40 ms (25 Hz) and became shorter with shorter ISIs (2.5∼20 ms). The correlation coefficient r2 for the peak latency and ISI was as high as 0.99, which suggested that sensory storage for the stimulation frequency accurately determined the Off-P50m latency. Statistical analysis revealed that the latency of all pairs, except for that between 200 and 400 Hz, was significantly different, indicating the very high temporal resolution of sensory storage at approximately 5 ms.

In the management of clinical low back pain (LBP), actual damage to lower back areas such as muscles, intervertebral discs etc. are normally targeted for therapy. However, LBP may involve not only sensory pain, but also underlying affective pain which may also play an important role overall in painful events. Therefore we hypothesized that visualization of a painful event may trigger painful memories, thus provoking the affective dimension of pain. The present study investigated neural correlates of affect processing in subjects with LBP (n = 11) and subjects without LBP (n = 11) through the use of virtual LBP stimuli. Whole brain functional magnetic resonance imaging (MRI) was performed for all subjects while they were shown a picture of a man carrying luggage in a half-crouching position. All subjects with LBP reported experiencing discomfort and 7 LBP subjects reported experiencing pain. In contrast to subjects without LBP, subjects with LBP displayed activation of the cortical area related to pain and emotions: the insula, supplementary motor area, premotor area, thalamus, pulvinar, posterior cingulate cortex, hippocampus, fusiform, gyrus, and cerebellum. These results suggest that the virtual LBP stimuli caused memory retrieval of unpleasant experiences and therefore may be associated with prolonged chronic LBP conditions.