Direct Inhibition of Microglia Activation by Pretreatment With Botulinum Neurotoxin A for the Prevention of Neuropathic Pain.

Peripheral injection of botulinum neurotoxin A (BoNT/A) has been demonstrated to have a long-term analgesic effect in treating neuropathic pain. Around peripheral nerves, BoNT/A is taken up by primary afferent neurons and inhibits neuropeptide release. Moreover, BoNT/A could also be retrogradely transported to the spinal cord.

Neural Activation During Tonic Pain and Interaction Between Pain and Emotion in Bipolar Disorder: An fMRI Study.

Pain and affective disorders have clear clinical relevance; however, very few studies have investigated the association between pain and bipolar disorder. This study investigated the brain activity of patients with bipolar disorder (BPs) undergoing tonic pain and assessed the interaction between pain and emotion. Ten BPs and ten healthy controls (HCs) were exposed to emotional pictures (positive, neutral, or negative), tonic pain only (pain session), and emotional pictures along with tonic pain (combined session).

Abnormal brain activation during emotion processing of euthymic bipolar patients taking different mood stabilizers.

Numerous functional magnetic resonance imaging studies have been conducted to elucidate emotion processing of patients with bipolar disorder (BD), but due to different inclusion criteria used, especially for the history of medication use, the results for euthymic BD patients are inconsistent. For this reason, brain functional effects of psychopharmacological treatments on BD patients have been investigated by numerous fMRI studies, but there is no existing report for brain functional effects of different mood stabilizers. In this study, we compared the emotion processing in BD patients treated by two popularly used mood stabilizer, lithium (N = 13; 30 ± 9 years) and valproate (N = 16; 33 ± 8 years), as well as healthy controls (HC; N = 16; 29 ± 7 years).

Electroacupuncture Stimulation of Language-Implicated Acupoint Tongli (HT 5) in Healthy Subjects: An fMRI Evaluation Study.

Objective: To explore brain activations associated with electroacupuncture simulation at Tongli (HT 5) and its comparison with brain activations during picture-naming task.

Methods: Twenty healthy subjects were enrolled in this study. Half of them received electroacupuncture stimulation at HT 5 (ACUP group) and the other half of them received stimulation at a nonmeridian sham acupoint (SHAM group).

Corrigendum: Placebo Analgesia Changes Alpha Oscillations Induced by Tonic Muscle Pain: EEG Frequency Analysis Including Data during Pain Evaluation.

[This corrects the article on p. 45 in vol. 10, PMID: 27242501.

Alterations in regional homogeneity of resting-state brain activity in patients with major depressive disorder screening positive on the 32-item hypomania checklist (HCL-32).

Background: Bipolar disorder (BD) is difficult to diagnose in the early stages of the illness, with the most frequent misdiagnosis being major depressive disorder (MDD). We aimed to use a regional homogeneity (ReHo) approach with resting-state functional magnetic resonance imaging (rs-fMRI) to investigate the features of spontaneous brain activity in MDD patients screening positive on the 32-item Hypomania Checklist (HCL-32).

Methods: Nineteen MDD patients screening positive (HCL-32(+); 9 males; 24.

Changes of gamma-band oscillatory activity to tonic muscle pain.

It is well know that phasic pain could induce suppression of alpha oscillations and enhancement of gamma oscillations. However, the cortical responses to tonic pain, especially tonic pain originating from deep tissue, which was proposed to better resemble the clinical pain, are not well understood. Here we aimed to investigate electroencephalographic (EEG) responses to tonic muscle pain.

Placebo Analgesia Changes Alpha Oscillations Induced by Tonic Muscle Pain: EEG Frequency Analysis Including Data during Pain Evaluation.

Placebo exhibits beneficial effects on pain perception in human experimental studies. Most of these studies demonstrate that placebo significantly decreased neural activities in pain modulatory brain regions and pain-evoked potentials. This study examined placebo analgesia-related effects on spontaneous brain oscillations.

Increased cerebellar activation after repetitive transcranial magnetic stimulation over the primary motor cortex in patients with multiple system atrophy.

Background: Previous review reported that the high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor area (M1) of Parkinson's disease (PD) patients could alleviate their symptoms. This study aimed to investigate the effect of rTMS over the left M1 of patients with multiple system atrophy (MSA).

Methods: Fifteen MSA patients were randomly assigned to receive a 10-session real (EP: group of experimental patients; n=7) or sham (CP: group of control patients; n=8) rTMS stimulation over two weeks.

Mechanism of Kinect-based virtual reality training for motor functional recovery of upper limbs after subacute stroke.

The Kinect-based virtual reality system for the Xbox 360 enables users to control and interact with the game console without the need to touch a game controller, and provides rehabilitation training for stroke patients with lower limb dysfunctions. However, the underlying mechanism remains unclear. In this study, 18 healthy subjects and five patients after subacute stroke were included.

Painful muscle stimulation preferentially activates emotion-related brain regions compared to painful skin stimulation.

Skin pain and muscle pain are categorically distinct from each other. While skin pain is a sharp, spatially localized sensation, muscle pain is a dull, poorly localized and more unpleasant one. We hypothesized that there are specific brain regions preferentially activated by muscle pain compared to skin pain.

Neuroimaging study of placebo analgesia in humans.

Placebo has been reported to exert beneficial effects in patients regarding the treatment of pain. Human functional neuroimaging technology can study the intact human brain to elucidate its functional neuroanatomy and the neurobiological mechanism of the placebo effect. Blood flow measurement using functional magnetic resonance imaging and positron emission tomography (PET) has revealed that analgesia is related to decreased neural activities in pain-modulatory brain regions, such as the rostral anterior cingulate cortex (rACC), insula, thalamus, and brainstem including periaqueductal gray (PAG) and ventromedial medulla.

Brain processing of the signals ascending through unmyelinated C fibers in humans: an event-related functional magnetic resonance imaging study.

Event-related functional magnetic resonance imaging was used to investigate brain processing of the signals ascending from peripheral C and Adelta fibers evoked by phasic laser stimuli on the right hand in humans. The stimulation of both C and Adelta nociceptors activated the bilateral thalamus, bilateral secondary somatosensory cortex, right (ipsilateral) middle insula, and bilateral Brodmann's area (BA) 24/32, with the majority of activity found in the posterior portion of the anterior cingulate cortex (ACC). However, magnitude of activity in the right (ipsilateral) BA32/8/6, including dorsal parts in the anterior portion of the ACC (aACC) and pre-supplementary motor area (pre-SMA), and the bilateral anterior insula was significantly stronger following the stimulation of C nociceptors than Adelta nociceptors.

Human brain processing and central mechanisms of pain as observed by electro- and magneto-encephalography.

We review the recent progress of electroencephalography (EEG) and magnetoencephalography (MEG) to elucidate pain perception mechanisms in humans, since EEG and MEG have an excellent temporal resolution in order of msec. MEG is more useful to detect activated areas following painful stimulation, because the spatial resolution of EEG is not very high. For recording activities following Adelta fiber stimulation relating to the first pain, painful CO2 laser stimulation is now widely used, but our new method, epidermal stimulation (ES), is also very useful.

Effects of distraction on magnetoencephalographic responses ascending through C-fibers in humans.

Objective: Using magnetoencephalography (MEG), we evaluated the cerebral regions relating to second pain perception ascending through C-fibers and investigated the effect of distraction on each region.

Methods: Thirteen normal subjects participated in this study. CO2 laser pulses were delivered to the dorsum of the left hand to selectively activate C-fibers.

Movements modulate cortical activities evoked by noxious stimulation.

To evaluate the effects of movement on cortical activities evoked by noxious stimulation, we recorded magnetoencephalography following noxious YAG laser stimulation applied to the dorsum of the left hand in normal volunteers. Results of the present study can be summarized as follows: (1) active movement of the hand ipsilateral to the side of noxious stimulation resulted in significant attenuation of both primary and secondary somatosensory cortices (SI and SII) in the hemisphere contralateral to the stimulated hand (cSI and cSII). Activity in the hemisphere ipsilateral to the side of stimulation (iSII) was not affected.

Pain processing within the primary somatosensory cortex in humans.

To investigate the processing of noxious stimuli within the primary somatosensory cortex (SI), we recorded magnetoencephalography following noxious epidermal electrical stimulation (ES) and innocuous transcutaneous electrical stimulation (TS) applied to the dorsum of the left hand. TS activated two sources sequentially within SI: one in the posterior bank of the central sulcus and another in the crown of the postcentral gyrus, corresponding to Brodmann's areas 3b and 1, respectively. Activities from area 3b consisted of 20- and 30-ms responses.

Microneurographic study of C fiber discharges induced by CO2 laser stimulation in humans.

We investigated C-fiber discharges and cerebral potentials evoked by weak CO(2) laser beams applied to a tiny skin area in five healthy subjects. Microneurography was performed from the peroneal nerve in the right popliteal area. Cerebral potentials were recorded from the Cz electrode referred to linked earlobes.

Sensory perception during sleep in humans: a magnetoencephalograhic study.

We reported the changes of brain responses during sleep following auditory, visual, somatosensory and painful somatosensory stimulation by using magnetoencephalography (MEG). Surprisingly, very large changes were found under all conditions, although the changes in each were not the same. However, there are some common findings.

Effects of sleep on pain-related somatosensory evoked magnetic fields in humans.

We investigated the effects of sleep on pain-related somatosensory evoked magnetic fields (SEFs) following painful electrical stimulation to identify the mechanisms generating them in both fast A-beta fibers relating to touch and slow A-delta fibers relating to pain. While the subjects were awake, non-painful and painful electrical stimulations were applied, and while asleep, painful stimulation was applied to the left index finger. During awake, five components (1M-5M) were identified following both non-painful and painful stimulation, but the 4M and 5M at around 70-100 ms and 140-180 ms, respectively, were significantly enhanced following painful stimulation.

Cerebral responses following stimulation of unmyelinated C-fibers in humans: electro- and magneto-encephalographic study.

There are two kinds of pain, a sharp pain ascending through Adelta fibers (first pain) and a second burning pain ascending though C fibers (second pain). By using a novel method, the application of a low intensity CO(2) laser beam to a tiny area of skin using a very thin aluminum plate with numerous tiny holes as a spatial filter, we succeeded in selectively stimulating unmyelinated C fibers of the skin in humans, and could record consistent and clear brain responses using electroencephalography (EEG) and magnetoencephalography (MEG). The conduction velocity (CV) of the C fibers of the peripheral nerve and spinal cord, probably spinothalamic tract (STT), is approximately 1-4 m/s, which is significantly slower than that of Adelta (approximately 10-15 m/s) and Abeta fibers (approximately 50-70 m/s).

Effects of sleep on pain-related somatosensory evoked potentials in humans.

We investigated effects of sleep on pain-related somatosensory evoked potentials (SEP) following painful electrical stimulation of the left index finger. The biggest advantage of this method is that signals ascending through both A-beta fibers relating to touch and A-delta fibers relating to pain can be recorded simultaneously. While the subject was awake, non-painful stimulation evoked early- and middle latency components, N20, P30 and N60, at the C4 electrode, and painful stimulation evoked not only early- and middle latency components at the C4 but also later pain-specific components, N130 and P240, at the Cz electrode.

Effects of attention, distraction and sleep on CO(2) laser evoked potentials related to C-fibers in humans.

Objectives: The objective of this study is to evaluate the effects of attention, distraction and sleep on CO(2) laser-evoked potentials (LEP) relating to C-fibers (ultra-late LEP).

Methods: Non-painful CO(2) laser pulses were delivered to a tiny skin area of the dorsum of the right hand. Ultra-late LEP were recorded from 10 normal subjects in 5 different conditions: control (wakefulness), attention, distraction, drowsiness and sleep (stage 2).