Age and sex effects on paired-pulse suppression and prepulse inhibition of auditory evoked potentials.

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.

Pre-emptive ice pack cryotherapy for reducing pain caused by long-acting deltoid injectable antipsychotic treatment: A single-center open-label study.

PURPOSE: This empirical study aims to investigate the efficacy of pre-emptive cryotherapy in reducing pain that is caused by the deltoid intramuscular (IM) injection of long-acting injectable (LAI) antipsychotics in clinical settings. PATIENTS AND METHODS: This study included 29 outpatients receiving LAI antipsychotic treatment. The evaluations of pain during (1) the usual procedure (control), (2) pre-emptive use of ice pack cryotherapy (pre-cooling), and (3) pre-emptive use of a room-temperature ice pack (pre-touching) were conducted using a numerical rating scale (NRS) for comparison. All patients were administered with LAI antipsychotics via deltoid IM. Furthermore, the results of the Positive and Negative Symptom Scale (PANSS), clinical global impressions (CGI) scale, and Global Assessment of Functioning (GAF) scale that were administered during the control procedure were evaluated. RESULTS: The median NRS pain scores during the IM injection of LAI antipsychotics were 4.0 (3.0-5.0), 2.0 (1.0-3.0), and 3.0 (2.5-6.0) for the control, pre-cooling, and pre-touching conditions, indicating a significant difference (p = 6.0 × 10-6). The NRS pain scores for the pre-cooling condition were significantly lower than those for the control and pre-touching conditions (p = 2.5 × 10-5 and 6.7 × 10-5, respectively). No significant correlation was observed between the NRS pain scores for the control condition and the PANSS, CGI scale, or GAF scale scores. Furthermore, no adverse events were recorded during the study period. CONCLUSION: Pain during the deltoid IM injection of LAI antipsychotics was found to be reduced by pre-emptive skin cooling. To date, this is the first study to confirm the effectiveness of pre-emptive cryotherapy for relieving such pain in clinical situations.

Long-Term Safety and Efficacy of Mirogabalin for Central Neuropathic Pain: A Multinational, Phase 3, 52-Week, Open-Label Study in Asia.

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 enhanced by beta-band subharmonics.

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.

Cortical activity during the wind-up of flexion reflex and pain: a magnetoencephalographic study using time-frequency analysis.

Wind-up is a nociceptive-specific phenomenon in which pain sensations are facilitated, in a frequency-dependent manner, by the repeated application of noxious stimuli of constant intensity, with invariant tactile sensations. Thus, cortical activities during wind-up could be an alteration associated with pain potentiation. We aimed to investigate somatosensory-evoked cortical responses and induced brain oscillations during wind-up by recording magnetoencephalograms. Wind-up was produced by the application of 11 consecutive electrical stimuli to the sural nerve, repeated at a frequency of 1 Hz without varying the intensity. The augmentation of flexion reflexes and pain rating scores were measured simultaneously as an index of wind-up. In the time-frequency analyses, the γ-band late event-related synchronization and the ß-band event-related desynchronization were observed in the primary somatosensory region and the bilateral operculo-insular region, respectively. Repetitive exposure to the stimuli enhanced these activities, along with an increase in the flexion reflex magnitude. The evoked cortical activity reflected novelty, with no alteration to these repetitive stimuli. Observed oscillations enhanced by repetitive stimulation at a constant intensity could reflect a pain mechanism associated with wind-up.

Mirogabalin for Central Neuropathic Pain After Spinal Cord Injury: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study in Asia.

BACKGROUND AND OBJECTIVES: Patients with spinal cord injury (SCI) commonly experience central neuropathic pain (CNeP), which is challenging to treat. Mirogabalin is effective for peripheral neuropathic pain, but evidence for CNeP is lacking. METHODS: This randomized, double-blind, placebo-controlled, phase 3 study investigated mirogabalin efficacy and safety for the treatment of CNeP in patients with traumatic SCI. Adult patients from 120 sites throughout Japan, Korea, and Taiwan were randomized (1:1) to receive placebo or mirogabalin (5 mg twice daily [BID] for 1 week, 10 mg BID for 1 week, and 10 or 15 mg BID for 12 weeks). Patients with moderate renal impairment received half the dosage. The primary efficacy endpoint was change from baseline in the weekly average daily pain score (ADPS) at week 14. The secondary endpoints included ADPS responder rates, the Short-Form McGill Pain Questionnaire (SF-MPQ), average daily sleep interference score (ADSIS), and Neuropathic Pain Symptom Inventory (NPSI). Adverse events were monitored for safety. RESULTS: Each treatment group comprised 150 patients. Mirogabalin elicited a statistical and clinically relevant improvement in change from baseline in the weekly ADPS at week 14 (least-squares mean difference [95% CI] vs placebo -0.71 [-1.08 to -0.34], p = 0.0001). Responder rates at week 14 were higher for mirogabalin than those for placebo (odds ratio [95% CI] 1.91 [1.11-3.27] for the ≥30% responder rate; 2.52 [1.11-5.71] for the ≥50% responder rate). Statistical improvements (i.e., least-squares mean difference [95% CI] vs placebo) were also observed in the SF-MPQ (-2.4 [-3.8 to -1.1]), ADSIS -0.71 (-1.04 to -0.38), and NPSI -7.7 (-11.1 to -4.4) scores. Most treatment-emergent adverse events were mild; no serious adverse drug reactions were reported. DISCUSSION: Mirogabalin elicited clinically relevant decreases in pain and was well tolerated, suggesting that mirogabalin is a promising treatment for patients with CNeP due to SCI. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov (NCT03901352); first submitted April 3, 2019; first patient enrolled March 14, 2019; available at clinicaltrials.gov/ct2/show/NCT03901352. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in adult patients with CNeP due to traumatic SCI, mirogabalin, 10 or 15 mg BID, effectively improves weekly ADPS at week 14.

Mechanisms of Short- and Long-Latency Sensory Suppression: Magnetoencephalography Study.

Prepulse inhibition (PPI) is sensory suppression whose mechanism (i.e., whether PPI originates from specific inhibitory mechanisms) remains unclear. In this study, we applied the combination of short-latency PPI and long-latency paired pulse suppression in 17 healthy subjects using magnetoencephalography to investigate the mechanisms of sensory suppression. Repeats of a 25-ms pure tone without a blank at 800 Hz and 70 dB were used for a total duration of 1600 ms. To elicit change-related cortical responses, the sound pressure of two consecutive tones in this series at 1300 ms was increased to 80 dB (Test). For the conditioning stimuli, the sound pressure was increased to 73 dB at 1250 ms (Pre 1) and 80 dB at 700 ms (Pre 2). Six stimuli were randomly presented as follows: (1) Test alone, (2) Pre 1 alone, (3) Pre 1 + Test, (4) Pre 2 + Test, (5) Pre 2 + Pre 1, and (6) Pre 2 + Pre 1 + Test. The inhibitory effects of the conditioning stimuli were evaluated using N100m/P200m components. The results showed that both Pre 1 and Pre 2 significantly suppressed the Test response. Moreover, the inhibitory effects of Pre 1 and Pre 2 were additive. However, when both prepulses were present, Pre 2 significantly suppressed the Pre 1 response, suggesting that the Pre 1 response amplitude was not a determining factor for the degree of suppression. These results suggested that the suppression originated from a specific inhibitory circuit independent of the excitatory pathway.

Relationship of loudness-dependent auditory evoked potentials with change-related cortical responses.

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.

A Minimally Invasive Method for Observing Wind-Up of Flexion Reflex in Humans: Comparison of Electrical and Magnetic Stimulation.

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.

Suppression of Low-Frequency Gamma Oscillations by Activation of 40-Hz Oscillation.

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.

Mechanisms of Long-Latency Paired Pulse Suppression: MEG Study.

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.

Separation from a bonded partner alters neural response to inflammatory pain in monogamous rodents.

Pain experience is known to be modified by social factors, but the brain mechanisms remain unspecified. We recently established an animal model of social stress-induced hyperalgesia (SSIH) using a socially monogamous rodent, the prairie vole, in which males separated from their female partners (loss males) became anxious and displayed exacerbated inflammatory pain behaviors compared to males with partners (paired males). In the present study, to explore the neural pathways involved in SSIH, a difference in neuronal activation in pain-related brain regions, or "pain matrix", during inflammatory pain between paired and loss males was detected using Fos immunoreactivity (Fos-ir). Males were paired with a female and pair bonding was confirmed in all subjects using a partner preference test. During formalin-induced inflammatory pain, both paired and loss males showed a significant induction of Fos-ir throughout the analyzed pain matrix components compared to basal condition (without injection), and no group differences in immunoreactivity were found among the injected males in many brain regions. However, the loss males had significantly lower Fos-ir following inflammatory pain in the medial prefrontal cortex and nucleus accumbens shell than the paired males, even though base Fos-ir levels were comparable between groups. Notably, both regions with different Fos-ir are major components of the dopamine and oxytocin systems, which play critical roles in both pair bonding and pain regulation. The present results suggest the possibility that pain exacerbation by social stress emerges through alteration of signaling in social brain circuitry.

A Novel Exercise Facilitation Method in Combination with Cognitive Behavioral Therapy Using the Ikiiki Rehabilitation Notebook for Intractable Chronic Pain: Technical Report and 22 Cases.

Recent clinical practice guidelines for chronic pain indicate, with a high evidence level, that the combination of exercise and cognitive behavioral therapy (CBT) is effective. The purpose of this study was to evaluate the effectiveness of an exercise facilitation method in combination with CBT using the "Ikiiki Rehabilitation Notebook" for patients with intractable chronic pain. "Ikiiki" means active in Japanese. A total of 22 cases with chronic low back (n = 13), lower extremity (n = 8), or neck (n = 1) pain were treated using this notebook. Two cases dropped out, leaving 22 cases. Each case was evaluated in terms of the numerical rating scale (NRS) of the pain, activities of daily living (ADL), pain catastrophizing scale (PCS), and quality of life (QOL) at pretreatment and post-treatment. The endpoint of the method was to achieve the long-term goals set by the patients. The mean treatment period was 11.2 months. The outcomes were as follows: improvement of presenteeism: nine cases; enhanced participation in hobbies: seven cases; improved school attendance: two cases; return to work: one case; improvement of self-care and/or self-efficacy: three cases. The NRS, ADL, PCS, and QOL were significantly improved after the treatment. This method is possibly valuable for educating patients about the cause and treatment of chronic pain and actively facilitating exercise and social participation. Further studies are needed to investigate the effectiveness of using this notebook for the patient with intractable chronic pain.

Conditioned Pain Modulation: Comparison of the Effects on Nociceptive and Non-nociceptive Blink Reflex.

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.

The Auditory Steady-State Response: Electrophysiological Index for Sensory Processing Dysfunction in Psychiatric Disorders.

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.

Changes in visual attentional behavior in complex regional pain syndrome: A preliminary study.

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.

Test-retest reliability of paired pulse suppression paradigm using auditory change-related response.

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.

A Pusher and a Clip Applied to Hind Paws Under Isoflurane Sedation to Evaluate Neuropathic Pain in a CCI Model.

Rodent behavior assessments have been developed to evaluate pain. However, their fidgety activity and reactivity to human contact make it hard to activate animals in a consistent manner and get uniform and trustworthy responses. The present study was performed on prairie voles (aged 8 weeks). Sham (7 male prairie voles) and chronic constriction injury (CCI) (8 male prairie voles) rodents were investigated before surgery and four and seven days later. Each animal was assessed for nociceptive behavior. Pressure and mechanical threshold tests were conducted by the application of three different pushers to the center of hind paws and arterial clips to the toes while sedated with isoflurane. The CCI affected right lower extremity prominently increased nociceptive behavior scores four and seven days after the experiment, and the CCI affected right hind paw prominently decreased pressure and mechanical threshold tests four and seven days after the experiment . The pressure and mechanical thresholds were relevant to the scorings of nociceptive behavior in CCI model animals.