Search

Paired pulse suppression is an electrophysiological method used to evaluate sensory suppression and often applied to patients with psychiatric disorders. However, it remains unclear whether the suppression comes from specific inhibitory mechanisms, refractoriness, or fatigue. In the present study, to investigate mechanisms of suppression induced by an auditory paired pulse paradigm in 19 healthy subjects, magnetoencephalography was employed. The control stimulus was a train of 25-ms pure tones of 65 dB SPL for 2500 ms. In order to evoke a test response, the sound pressure of two consecutive tones at 2200 ms in the control sound was increased to 80 dB (Test stimulus). Similar sound pressure changes were also inserted at 1000 (CS2) and 1600 (CS1) ms as conditioning stimuli. Four stimulus conditions were used; (1) Test alone, (2) Test + CS1, (3) Test + CS1 + CS2, and (4) Test + CS2, with the four sound stimuli randomly presented and cortical responses averaged at least 100 times for each condition. The baseline-to-peak and peak-to-peak amplitudes of the P50m, N100m, and P200m components of the test response were compared among the four conditions. In addition, the response to CS1 was compared between conditions (2) and (3). The results showed significant test response suppression by CS1. While the response to CS1 was significantly suppressed when CS2 was present, it did not affect suppression of the test response by CS1. It was thus suggested that the amplitude of the response to a conditioning stimulus is not a factor to determine the inhibitory effects of the test response, indicating that suppression is due to an external influence on the excitatory pathway.

Gamma oscillations have received considerable attention owing to their association with cognitive function and various neuropsychiatric disorders. However, interactions of gamma oscillations at different frequency bands in humans remain unclear. In the present magnetoencephalographic study, brain oscillations in a wide frequency range were examined using a time-frequency analysis during the 20-, 30-, 40-, and 50-Hz auditory stimuli in 21 healthy subjects. First, dipoles for auditory steady-state response (ASSR) were estimated and interaction among oscillations at 10–60 Hz was examined using the source strength waveforms. Results showed the suppression of ongoing low-gamma oscillations at approximately 30 Hz during stimulation at 40 Hz. Second, multi-dipole analyses suggested that the main dipole for ASSR and dipoles for suppressed low-frequency gamma oscillations were distinct. Third, an all-sensor analysis was performed to clarify the distribution of the 40-Hz ASSR and suppression of low-frequency gamma oscillations. Notably, the area of suppression surrounded the center of the 40-Hz ASSR and showed a trend of extending to the vertex, indicating that different groups of neurons were responsible for these two gamma oscillations and that the 40-Hz oscillation circuit have specific inhibitory innervation to the low-gamma circuit.

Haptic memory briefly retains somatosensory information for later use; however, how and which cortical areas are affected by haptic memory remain unclear. We used change‐related cortical responses to investigate the relationship between the somatosensory cortex and haptic memory objectively. Electrical pulses, at 50 Hz with a duration of 500 ms, were randomly applied to the second, third, and fourth fingers of the right and left hands at an even probability every 800 ms. Each stimulus was labeled as D (preceded by a different side) or S (preceded by the same side). The D stimuli were further classified into 1D, 2D, and 3D, according to the number of different preceding stimuli. The S stimuli were similarly divided into 1S and 2S. The somatosensory‐evoked magnetic fields obtained were divided into four components via a dipole analysis, and each component's amplitudes were measured using the source strength waveform. The results showed that the preceding event did not affect the amplitude of the earliest 20–30 ms response in the primary somatosensory cortex. However, in the subsequent three components, the cortical activity amplitude was largest in 3D, followed by 2D, 1D, and S. These results indicate that such modulatory effects occurred somewhere in the somatosensory processing pathway higher than Brodmann's area 3b. To the best of our knowledge, this is the first study to demonstrate the existence of haptic memory for somatosensory laterality and its impact on the somatosensory cortex using change‐related cortical responses without contamination from peripheral effects., Electrical pulses were randomly applied to the right and left hands. The somatosensory‐evoked magnetic fields obtained were divided into four components (early SI, middle SI, late SI, and cSII). For each component, there are five event histories (1D, 2D, 3D, 1S, and 2S), which indicate the number of different (D) or similar (S) tactile stimuli that precede the probe stimulus.

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.

Paired-pulse suppression refers to attenuation of neural activity in response to a second stimulus and has a pivotal role in inhibition of redundant sensory inputs. Previous studies have suggested that cortical responses to a somatosensory stimulus are modulated not only by a preceding same stimulus, but also by stimulus from a different submodality. Using magnetoencephalography, we examined somatosensory suppression induced by three different conditioning stimuli. The test stimulus was a train of electrical pulses to the dorsum of the left hand at 100 Hz lasting 1500 ms. For the pulse train, the intensity of the stimulus was abruptly increased at 1200 ms. Cortical responses to the abrupt intensity change were recorded and used as the test response. Conditioning stimuli were presented at 600 ms as pure tones, either innocuous or noxious electrical stimulation to the right foot. Four stimulus conditions were used: (1) Test alone, (2) Test + auditory stimulus, (3) Test + somatosensory stimulus, and (4) Test + nociceptive stimulus. Our results showed that the amplitude of the test response was significantly smaller for conditions (3) and (4) in the secondary somatosensory cortex contralateral (cSII) and ipsilateral (iSII) to the stimulated side as compared to the response to condition (1), whereas the amplitude of the response in the primary somatosensory cortex did not differ among the conditions. The auditory stimulus did not have effects on somatosensory change-related response. These findings show that somatosensory suppression was induced by not only a conditioning stimulus of the same somatosensory submodality and the same cutaneous site to the test stimulus, but also by that of a different submodality in a remote area.

Although conditioned pain modulation (CPM) is considered to represent descending pain inhibitory mechanisms triggered by noxious stimuli applied to a remote area, there have been no previous studies comparing CPM between pain and tactile systems. In this study, we compared CPM between the two systems objectively using blink reflexes. Intra-epidermal electrical stimulation (IES) and transcutaneous electrical stimulation (TS) were applied to the right skin area over the supraorbital foramen to evoke a nociceptive or a non-nociceptive blink reflex, respectively, in 15 healthy males. In the test session, IES or TS were applied six times and subjects reported the intensity of each stimulus on a numerical rating scale (NRS). Blink reflexes were measured using electromyography (R2). The first and second sessions were control sessions, while in the third session, the left hand was immersed in cold water at 10 °C as a conditioning stimulus. The magnitude of the R2 blink and NRS scores were compared among the sessions by 2-way ANOVA. Both the NRS score and nociceptive R2 were significantly decreased in the third session for IES, with a significant correlation between the two variables; whereas, TS-induced non-nociceptive R2 did not change among the sessions. Although the conditioning stimulus decreased the NRS score for TS, the CPM effect was significantly smaller than that for IES (p = 0.002). The present findings suggest the presence of a pain-specific CPM effect to a heterotopic noxious stimulus.

Purpose The 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 methods Eight 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. Results In 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. Conclusion Some 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.

Background Sensory suppression is an important brain function for appropriate processing of information and is known to be impaired in patients with various types of mental illness. Long latency suppression which is a paradigm using change-related cortical response with repeated paired pulses embedded in a train of conditioning pulses is a factor used to measure sensory suppression. New method The present study assessed the test-retest reliability of long-latency suppression in latency, amplitude, and suppression rate of the P50, N100, and P200 components of auditory evoked potentials in 35 healthy adults. The sound stimulus was repeats of a 25-ms pure tone at 65 dB and 2000 ms in total duration, during which the sound pressure level was increased to 80 dB twice at 1100 ms and 1700 ms. Measurements were performed twice and the validity of the findings was evaluated using intra-class correlations. Results The results showed high intra-class correlation (ICC) values (>0.7) for the amplitude of all components, except for P50 (0.44), while latency also showed high ICC values (>0.66), except for P50 (0.20). In addition, the suppression rate showed good reproducibility for the N100-P200 component (0.60). Comparison with Existing Method The method can be performed with a short inspection time of approximately 5 min and provides high ICC values. In addition, it may reflect suppression mechanisms different from those relating to existing methods. Conclusion These results support the use of long latency suppression as a biomarker in clinical settings.

Prepulse inhibition (PPI) is a neurological phenomenon in which a weak initial stimulus reduces the level of responses to a subsequent stronger stimulus. Although acoustic startle reflexes are usually used for PPI examinations, recent studies have observed similar phenomena with event-related cortical potentials. In the present study, test-retest reliability of PPI measured using auditory change-related cortical responses was assessed in 35 healthy adults. Four sound stimuli were randomly presented at an even probability; Standard, Test alone, Prepulse alone, and Test + Prepulse. The Standard stimulus was a train of 25-ms tone pulses at 70 dB for 650 ms, while for Test alone and Prepulse alone, the sound pressure was increased to 80 dB at 350 ms and 73 dB at 300 ms, respectively. Measurements were performed twice with at least 7 days separation, and validity was evaluated using intra-class correlation (ICC) for latency, amplitude, and suppression rate of the P50, N100, and P200 components. The results showed high ICC values for the latency and amplitude of nearly all components, except for response to Prepulse alone (0.3–0.6). Furthermore, ICC for suppression rate was greater than 0.5 for the peak-to-peak amplitude. Good reproducibility for N100 and P200 components was obtained with this method. The present results support the PPI paradigm as a reliable tool for clinical measurements of inhibitory functions.

A weak preceding sound stimulus attenuates the startle response evoked by an intense sound stimulus. Like startle reflexes, change-related auditory responses are suppressed by a weak leading stimulus (ie, a prepulse). We aim to examine whether a prepulse inhibits cerebral responses to the sound offset and how the prepulse magnitude affects the degree of the prepulse inhibition (PPI). Using magnetoencephalography, we recorded the Off-P50m elicited by an offset of a train sound of 100-Hz clicks in 12 healthy subjects. A single click slightly louder (+1.5, +3, or +5 dB) than the background sound of 80 dB was inserted 50 ms before the sound offset as a prepulse. We performed a dipole source analysis of the Off-P50m, and we measured its latency and amplitude using the source strength waveforms. The origin of the Off-P50m was estimated to be the auditory cortex on both hemispheres. The Off-P50m was clearly attenuated by the prepulses, and the degree of PPI was greater with a louder prepulse. The Off-P50m is considered to be a simple change-related response, which does not overlap with a processing of incoming sounds. Thus, the Off-P50m and its PPI comprise a valuable tool for investigating the neural inhibitory system.

Objective The aim of this study was to find pain-related brain activity which corresponds to self-report pain ratings based on degree of response and repeatability. Methods Three painful mechanical stimuli were applied to the right hands of 25 healthy volunteers using monofilaments (forces of 0.98 N, 2.94 N, and 5.88 N). Simultaneously, brain activities were evaluated using functional MRI for a constant stimulus conducted three times in a session. In first assessment, the average percent signal change (PSC) of neuronal response was measured for each region of interest (ROI), secondary repeatability of PSC conducted three times over the session was evaluated for each ROI. Results Although the average PSCs for trice stimuli conducted in one session increased in accordance with pain ratings in the somatosensory cortex (S1) and anterior cingulate cortex (ACC), there was a different response between S1 and ACC when subjects rated intense pain; a stable response in S1 against a variable response in ACC. Conclusions These results imply that there are different cognitive responses between sensory discrimination and affective component to constant painful stimulus each time. Significance Consistency of brain activity based on PSC may be an important biomarker which, along with its neuronal activity, gauges self-report pain ratings.

Cross-modal interaction occurs during the early stages of processing in the sensory cortex; however, its effect on neuronal activity speed remains unclear. We used magnetoencephalography to investigate whether auditory stimulation influences the initial cortical activity in the primary somatosensory cortex. A 25-ms pure tone was randomly presented to the left or right side of healthy volunteers at 1000 ms when electrical pulses were applied to the left or right median nerve at 20 Hz for 1500 ms because we did not observe any cross-modal effect elicited by a single pulse. The latency of N20 m originating from Brodmann’s area 3b was measured for each pulse. The auditory stimulation significantly shortened the N20 m latency at 1050 and 1100 ms. This reduction in N20 m latency was identical for the ipsilateral and contralateral sounds for both latency points. Therefore, somatosensory–auditory interaction, such as input to the area 3b from the thalamus, occurred during the early stages of synaptic transmission. Auditory information that converged on the somatosensory system was considered to have arisen from the early stages of the feedforward pathway. Acceleration of information processing through the cross-modal interaction seemed to be partly due to faster processing in the sensory cortex.

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.

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.

Pain-VAS is quite subjective as a scale, but has a tendency to assume differences in repeatability in accordance with perceived pain intensity. The aim of the present study was to investigate the repeatability of regional differences with ratings of pain-VAS. Three experimental mechanical stimuli were applied to twenty seven healthy volunteers across four sessions over four weeks within individuals. The same stimuli were also simultaneously measured in the same manner with an electric balance. The magnitude of mechanical stimuli was determined by 100 g, 300 g, and 600 g monofilaments. Standard deviations (SDs) across measurements with an electric balance showed a regular increase with stimulus magnitude, while coefficient variations (CVs) were constant in each stimulus. On the other hand, although SDs across pain-VAS measurements were significantly greater with the 300 g filament than with the 100 g and 600 g filaments, CVs showed a regular decrease in magnitude of stimulus. These results showed that the CVs of repeated measurement with electric balance were consistent regardless of stimulus intensity, in contrast, CVs of pain-VAS decreased with greater pain rating averaged by repeated measurement. These results suggest that a low rating in pain-VAS is inherently less objective, indicating poor repeatability. In contrast, a high rating in pain-VAS is more objective with better repeatability for experimental pain perception.

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 ( rs = .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.

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.

Comprehensive programs for chronic pain management provided at multidisciplinary clinics have been shown to be successful in Western countries. However, similar results have not yet been reported in Japan, and it is unclear whether these results are applicable to the Japanese culture. Accordingly, the authors report the results of the ‘Chronic Pain Class’, a program initiated at a multidisciplinary pain centre in Nagakute, Japan., 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

To test the hypothesis that the N1 component of auditory evoked potentials (AEPs) is one form of the change-related response elicited by an abrupt change in sound pressure from a silent background, two AEP experiments were conducted. Change-N1 was evoked by a test stimulus at 70dB following a 3-s conditioning stimulus of 0-69dB. On-N1 was evoked by the test sound alone at various sound pressures. As the physical difference between stimuli increased, the amplitude of Change-N1 increased, and the latency shortened. The amplitude and latency of On-N1 showed a similar pattern to the Change-N1 response. These results support the idea that On-N1 is a change-related component elicited by a sound pressure change.

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.

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.

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.

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.

Objective Metastatic bone pain is characteristic of cancer pain and is a form of refractory cancer pain, as the pain includes not only nociceptive but also neuropathic pain. Although some drugs are effective in the management of painful bone metastases, pain while moving is one of the most refractory forms of pain. Although pulsed radiofrequency (RF) dramatically reduces neuropathic pain, chronic pain, and vertebral metastatic pain, the number of cases reported in these studies was very small (five or less). Design Case report. Setting Single pain center. Patients Fifteen patients suffering from intractable vertebral metastatic pain. Interventions Dorsal root ganglion (DRG) pulsed RF. Outcome Measures A numerical rating scale (NRS) of pain at rest and while moving. Results Almost all patients experienced sound pain relief after the pulsed RF treatment. There were no severe side effects reported. Conclusion DRG pulsed RF procedure provided sound pain relief for patients with intractable vertebral metastatic pain. Metastatic bone pain is characteristic of cancer pain and is a form of refractory cancer pain, as the pain includes not only nociceptive but also neuropathic pain. Although some drugs are effective in the management of painful bone metastases, pain while moving is one of the most refractory forms of pain. DRG pulsed RF procedure provided sound pain relief for patients with intractable vertebral metastatic pain.

The rapid detection of changes in sensory information is an essential process for survival. Individual humans are thought to have their own intrinsic preattentive responsiveness to sensory changes. Here we sought to determine the relationship between auditory change-related responses and personality traits, using event-related potentials. A change-related response peaking at approximately 120 ms (Change-N1) was elicited by an abrupt decrease in sound pressure (10 dB) from the baseline (60 dB) of a continuous sound. Sixty-three healthy volunteers (14 females and 49 males) were recruited and were assessed by the Temperament and Character Inventory (TCI) for personality traits. We investigated the relationship between Change-N1 values (amplitude and latency) and each TCI dimension. The Change-N1 amplitude was positively correlated with harm avoidance scores and negatively correlated with the self-directedness scores, but not with other TCI dimensions. Since these two TCI dimensions are associated with anxiety disorders and depression, it is possible that the change-related response is affected by personality traits, particularly anxiety- or depression-related traits.

Background 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. Objectives 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. Methods We conducted a cross-sectional postal survey in a sample of 6000 adults aged ≥20 years. The response rate was 43.8%. Results 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). Conclusions 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.

Purpose Apparent organic abnormalities are sometimes not identified among patients suffering from chronic pain in the craniocervical region. In some cases, parafunctional activities (PAs) are recognized. PAs are nonfunctional oromandibular activities that include jaw clenching and bruxism, but are considered as factors that contribute to craniomandibular disorders (CMDs). It is now recognized that PAs and CMDs influence musculoskeletal conditions of the upper quarter. Exercise therapy (ET) to improve jaw movement and psychological intervention (PI) to reduce PAs are useful for PAs and CMDs. We hypothesized that ET and PI would be effective for craniocervical pain without organic abnormalities. Methods Thirty-nine subjects suffering from craniocervical chronic pain were allocated into 3 groups: The control group received only pharmacological treatment; the ET group received jaw movement exercise (JME); and the ET-PI group received JME and PI. Pain and jaw movement were evaluated using a numerical rating scale (NRS). Results After interventions, the NRS scores were significantly lower in the ET-PI group, compared with those in the other groups. Jaw movement improved 100% in the ET group, 92% in the ET-PI group, and 0% in the control group. Conclusion A combination of jaw exercise and psychological intervention to reduce parafunctional activities is more effective than jaw exercise alone for the improvement of craniocervical pain without apparent organic abnormalities.

Pain drawings have frequently been used for documentation of pain and a convenient diagnosis tool. Pain drawings were found to be associated with psychological states in chronic patients with low back pain. Few researchers have investigated pain drawings except in low back pain. The aim of this study was to investigate the pain, pain drawings, psychological characteristics, and pain interference in the head, neck-shoulder (NS), and low-back/lower-limb (LB-LL) regions among patients with chronic pain.We included a total of 291 patients with new chronic pain (headache, 62; NS pain, 87; LB-LL pain, 142). The pain drawings and scores of 10-cm Visual Analogue Scale (VAS), Hospital Anxiety and Depression Scale (HADS), Pain Catastrophizing Scale (PCS), Short-Form McGill Pain Questionnaire (SF-MPQ), and Pain Disability Assessment Scale (PDAS) were extracted from medical records. A subset of 60 pain drawings was scored by senior and junior evaluators to assess inter-rater agreement. We investigated the correlation between pain drawings and VAS, HADS, PCS, SF-MPQ, and PDAS in each body region group at the initial visit. Moreover, almost all patients received nonsurgical treatment as a follow-up and were investigated using VAS after treatment.The reliability of pain drawings was substantial with an interevaluator reliability in headache, NS, and LB-LL pain. Nonorganic pain drawings were associated with psychological disturbances in NS and LB-LL pain, but not headache. Poor outcomes were associated with nonorganic drawings in LB-LL pain, but not in the case of headache or NS pain.Our results suggest that the characteristics of patients with nonorganic drawings differ according to body regions.

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.

Pain is a common reason for seeking health care and chronic pain is a common comorbidity in psychiatric disorders. In clinical practice, we encounter many patients with chronic pain; however, before initiating pain treatment, we should conduct detailed analysis of psychiatric symptoms, such as perception, memory, thought and mood disturbances or behavioral problems. We should also determine the frequency of occurrence of mental disorders in patients with pain, especially those with chronic pain, such as in mood, anxiety, pain, personality, and developmental disorders, and dementia. Current understanding of the intricate relationship between chronic pain and psychiatric issues not only provides opportunities for designing appropriate treatment but also raises good and new questions for future pain research.

Objective In contrast to tactile inputs, the organization and processing of nociceptive inputs in the primary somatosensory cortex (S1) remain largely unexplored. Few studies have examined the arrangement of nociceptive inputs in S1. The aim of this study was to investigate the representation of nociceptive inputs in the human cortex, including the somatosensory and posterior parietal cortices, from widely separated cutaneous sites. Methods We examined the somatotopic organization of the nociceptive system in S1, opercular and posterior parietal cortices by measuring the magnetoencephalographic responses (somatosensory-evoked magnetic fields) of four healthy controls in response to intraepidermal electrical stimulation applied to the face, neck, back, elbow, wrist, hand, finger, knee, and foot, which selectively activated the Aδ fibers. Results Magnetoencephalography demonstrated clear somatotopy in the S1 responses to noxious stimuli, with the foot representation in the extreme posteromedial position of S1 and the facial area in the extreme anterolateral position. There was little evidence of any clear somatotopic organization in the secondary somatosensory and posterior parietal cortices. Conclusion These findings suggest that the nociceptive system uses the large body surface map in S1. Significance This is the first MEG study to demonstrate the cortical representation of nociceptive inputs in the human S1. We showed that widely separated cutaneous sites clearly supported Penfield’s homunculus.

We report on the use of pulsed radiofrequency (RF) within the plexus for the management of intractable pain in three patients with metastatic or invasive plexopathy. The patients were a 38-year-old woman with a history of breast cancer 6 years earlier whose computed tomography (CT) scans revealed a mass lesion at the infraclavicular part of the right brachial plexus, a 68-year-old man diagnosed with advanced lung cancer whose CT scans revealed a bone metastasis in the right humerus invading the axillary region of the right brachial plexus, and a 67-year-old woman diagnosed with advanced lung cancer whose CT scans revealed a bone metastasis in the left humerus invading the axillary region of the left brachial plexus. Ultrasound-guided pulsed RF was performed within the interscalene brachial plexus. During the follow-up period, their intractable pain was moderately controlled.

Nicotine is known to have enhancing effects on some aspects of attention and cognition. The purpose of the present study was to elucidate the effects of nicotine on pre-attentive change-related cortical activity. Change-related cortical activity in response to an abrupt increase (3 dB) and decrease (6 dB) in sound pressure in a continuous sound was recorded by using magnetoencephalography. Nicotine was administered with a nicotine gum (4 mg of nicotine). Eleven healthy nonsmokers were tested with a double-blind and placebo-controlled design. Effects of nicotine on the main component of the onset response peaking at around 50 ms (P50m) and the main component of the change-related response at around 120 ms (Change-N1m) were investigated. Nicotine failed to affect P50m, while it significantly increased the amplitude of Change-N1m evoked by both auditory changes. The magnitude of the amplitude increase was similar among subjects regardless of the magnitude of the baseline response, which resulted in the percent increase of Change-N1m being greater for subjects with Change-N1m of smaller amplitude. Since Change-N1m represents a pre-attentive automatic process to encode new auditory events, the present results suggest that nicotine can exert beneficial cognitive effects without a direct impact on attention.

Celiac plexus block (CPB) can be used for treating intra-abdominal visceral pain syndromes. The celiac plexus is the largest plexus of the sympathetic nervous system. Several nerve blocks have a marked effect on autonomic nervous activity. Furthermore, stellate ganglion block changes cardiac autonomic nervous activity. Thus, CPB could influence the sympathetic activity of the cardiac plexus. The aim of the present study was to see whether CPB modulated heart rate variability (HRV) in patients with pancreatic cancer.Twelve patients received neurolytic CPB using 14 ml absolute alcohol. Data recorded in a palm-sized electrocardiographic unit were analyzed for HRV.CPB using a neurolytic solution did not induce any significant changes in the low-frequency (LF)/high-frequency (HF) ratio of HRV (LF/HF, P = 0.4642). Furthermore, the procedure did not induce any significant changes in blood pressure (systolic, P = 0.5051; diastolic, P = 0.5180).CPB did not induce any significant changes in HRV or hemodynamics.

Quickly detecting changes in the surrounding environment is one of the most important functions of sensory processing. Comparison of a new event with preceding sensory conditions is necessary for the change-detection process. A sudden change in a continuous sound elicits auditory evoked potentials that peak approximately 100 ms after the onset of the change (Change-N1). In the present study, we recorded Change-N1 under an oddball paradigm in 19 healthy subjects using an abruptly moving sound (SM-stimulus) as a deviant stimulus and investigated effects of the probability of the SM-stimulus to reveal whether Change-N1 is a memory-based response. We compared the amplitude and latency of Change-N1 elicited by the SM-stimulus among three probability conditions (33, 50 and 100%). As the probability of the SM-stimulus decreased, the amplitude of Change-N1 increased and its latency decreased. The present results indicate that the preceding sensory history affects Change-N1 elicited by the SM-stimulus.

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.

Painful neuropathic conditions of cancer pain often show little response to nonopioid and opioid analgesics but may be eased by antidepressants and anticonvulsants. Although gabapentin is effective in the treatment of neuropathic pain in patients with cancer, some patients experience intolerable side effects sufficient to warrant discontinuation. The aim of this study was to see whether low-dose gabapentin is effective in treating cancer-related neuropathic pain when combined with low-dose imipramine. Fifty-two cancer patients diagnosed as having neuropathic pain were allocated into four groups: G400-I group took gabapentin 200 mg and imipramine 10 mg every 12 h orally; G400 group took gabapentin 200 mg every 12 h orally; G800 group took gabapentin 400 mg every 12 h orally; I group took imipramine 10 mg every 12 h orally. Low-dose gabapentin–imipramine significantly decreased the total pain score and daily paroxysmal pain episodes. Several patients developed mild adverse symptoms in the four groups, and three patients discontinued treatment due to severe adverse events in the G800 group. Low-dose gabapentin–antidepressant combination with opioids was effective in managing neuropathic cancer pain without severe adverse effects.

Background Prepulse inhibition (PPI) of the startle response is an important tool to investigate the biology of schizophrenia. PPI is usually observed by use of a startle reflex such as blinking following an intense sound. A similar phenomenon has not been reported for cortical responses. Results In 12 healthy subjects, change-related cortical activity in response to an abrupt increase of sound pressure by 5 dB above the background of 65 dB SPL (test stimulus) was measured using magnetoencephalography. The test stimulus evoked a clear cortical response peaking at around 130 ms (Change-N1m). In Experiment 1, effects of the intensity of a prepulse (0.5 ~ 5 dB) on the test response were examined using a paired stimulation paradigm. In Experiment 2, effects of the interval between the prepulse and test stimulus were examined using interstimulus intervals (ISIs) of 50 ~ 350 ms. When the test stimulus was preceded by the prepulse, the Change-N1m was more strongly inhibited by a stronger prepulse (Experiment 1) and a shorter ISI prepulse (Experiment 2). In addition, the amplitude of the test Change-N1m correlated positively with both the amplitude of the prepulse-evoked response and the degree of inhibition, suggesting that subjects who are more sensitive to the auditory change are more strongly inhibited by the prepulse. Conclusions Since Change-N1m is easy to measure and control, it would be a valuable tool to investigate mechanisms of sensory gating or the biology of certain mental diseases such as schizophrenia.

Background Although magnesium ions (Mg2+) are known to display many similar features to other 2+ charged cations, they seem to have quite an important and unique role in biological settings, such as NMDA blocking effect. However, the role of Mg2+ in the neural transmission system has not been studied as sufficiently as calcium ions (Ca2+). To clarify the sensory effects of Mg2+ in peripheral nervous systems, sensory changes after intradermal injection of Mg2+ were studied in humans. Methods Magnesium sulphate, magnesium chloride and saline were injected into the skin of the anterior region of forearms in healthy volunteers and injection-induced irritating pain ("irritating pain", for short), tactile sensation, tactile pressure thresholds, pinch-pain changes and intolerable heat pain thresholds of the lesion were monitored. Results Flare formation was observed immediately after magnesium sulphate or magnesium chloride injection. We found that intradermal injections of magnesium sulphate and magnesium chloride transiently caused irritating pain, hypesthesia to noxious and innocuous mechanical stimulations, whereas secondary hyperalgesia due to mechanical stimuli was not observed. In contrast to mechanical stimuli, intolerable heat pain-evoking temperature was significantly decreased at the injection site. In addition to these results, spontaneous pain was immediately attenuated by local cooling. Conclusion Membrane-stabilizing effect and peripheral NMDA-blocking effect possibly produced magnesium-induced mechanical hypesthesia, and extracellular cation-induced sensitization of TRPV1 channels was thought to be the primary mechanism of magnesium-induced heat hyperalgesia.

Background The rapid detection of sensory change is important to survival. The process should relate closely to memory since it requires that the brain separate a new stimulus from an ongoing background or past event. Given that sensory memory monitors current sensory status and works to pick-up changes in real-time, any change detected by this system should evoke a change-related cortical response. To test this hypothesis, we examined whether the single presentation of a sound is enough to elicit a change-related cortical response, and therefore, shape a memory trace enough to separate a subsequent stimulus. Results Under a paradigm where two pure sounds 300 ms in duration and 800 or 840 Hz in frequency were presented in a specific order at an even probability, cortical responses to each sound were measured with magnetoencephalograms. Sounds were grouped to five events regardless of their frequency, 1D, 2D, and 3D (a sound preceded by one, two, or three different sounds), and 1S and 2S (a sound preceded by one or two same sounds). Whereas activation in the planum temporale did not differ among events, activation in the superior temporal gyrus (STG) was clearly greater for the different events (1D, 2D, 3D) than the same event (1S and 2S). Conclusions One presentation of a sound is enough to shape a memory trace for comparison with a subsequent physically different sound and elicits change-related cortical responses in the STG. The STG works as a real-time sensory gate open to a new event.

Background The detection of any abrupt change in the environment is important to survival. Since memory of preceding sensory conditions is necessary for detecting changes, such a change-detection system relates closely to the memory system. Here we used an auditory change-related N1 subcomponent (change-N1) of event-related brain potentials to investigate cortical mechanisms underlying change detection and echoic memory. Results Change-N1 was elicited by a simple paradigm with two tones, a standard followed by a deviant, while subjects watched a silent movie. The amplitude of change-N1 elicited by a fixed sound pressure deviance (70 dB vs. 75 dB) was negatively correlated with the logarithm of the interval between the standard sound and deviant sound (1, 10, 100, or 1000 ms), while positively correlated with the logarithm of the duration of the standard sound (25, 100, 500, or 1000 ms). The amplitude of change-N1 elicited by a deviance in sound pressure, sound frequency, and sound location was correlated with the logarithm of the magnitude of physical differences between the standard and deviant sounds. Conclusions The present findings suggest that temporal representation of echoic memory is non-linear and Weber-Fechner law holds for the automatic cortical response to sound changes within a suprathreshold range. Since the present results show that the behavior of echoic memory can be understood through change-N1, change-N1 would be a useful tool to investigate memory systems.