The effect of observational learning on the development of central sensitization

Watching other people in pain may affect one’s own experience of pain. It is unknown whether it can also modulate secondary mechanical hypersensitivity. We have addressed this question in two experiments in healthy human volunteers. In experiment 1 we tested, on a large sample (N=83), five videos of a model demonstrating high or low pain during high frequency stimulation (HFS) of the skin, a procedure known to induce secondary mechanical hypersensitivity. The aim was to select the two videos rated with the highest and lowest expected pain and fear (high pain and low pain videos). Morevoer, we have explored the correlation between empathy and fear scores. In experiment 2 (N=44), two groups of participants were randomly allocated to watching either the low or the high pain video, and subsequently underwent HFS. The high pain video group reported increased pain during HFS. The two groups differed in the magnitude of secondary mechanical hypersensitivity after HFS, but the unpleasantness scores for mechanical stimulation after HFS, as well as spread of hyperalgesia were not statistically different. Empathy scores correlated positively with fear reports in experiment 1 but not experiment 2. Unexpectedly, we found higher scores of fear of pain for the high pain video only in experiment 1. In summary, observational learning of a model demonstrating high pain seems to have a stastistically significant but small effect on pinprick hypersensitivity. Its operating mechanisms remain partially elusive.

A Fully Implantable Miniaturized Liquid Crystal Polymer (LCP)-Based Spinal Cord Stimulator for Pain Control

Spinal cord stimulation is a therapy to treat the severe neuropathic pain by suppressing the pain signal via electrical stimulation of the spinal cord. The conventional metal packaged and battery-operated implantable pulse generator (IPG) produces electrical pulses to stimulate the spinal cord. Despite its stable operation after implantation, the implantation site is limited due to its bulky size and heavy weight. Wireless communications including wireless power charging is also restricted, which is mainly attributed to the electromagnetic shielding of the metal package. To overcome these limitations, here, we developed a fully implantable miniaturized spinal cord stimulator based on a biocompatible liquid crystal polymer (LCP). The fabrication of electrode arrays in the LCP substrate and monolithically encapsulating the circuitries using LCP packaging reduces the weight (0.4 g) and the size (the width, length, and thickness are 25.3, 9.3, and 1.9 mm, respectively). An inductive link was utilized to wirelessly transfer the power and the data to implanted circuitries to generate the stimulus pulse. Prior to implantation of the device, operation of the pulse generator was evaluated, and characteristics of stimulation electrode such as an electrochemical impedance spectroscopy (EIS) were measured. The LCP-based spinal cord stimulator was implanted into the spared nerve injury rat model. The degree of pain suppression upon spinal cord stimulation was assessed via the Von Frey test where the mechanical stimulation threshold was evaluated by monitoring the paw withdrawal responses. With no spinal cord stimulation, the mechanical stimulation threshold was observed as 1.47 ± 0.623 g, whereas the stimulation threshold was increased to 12.7 ± 4.00 g after spinal cord stimulation, confirming the efficacy of pain suppression via electrical stimulation of the spinal cord. This LCP-based spinal cord stimulator opens new avenues for the development of a miniaturized but still effective spinal cord stimulator.

Prevention of trigeminocardiac reflex-induced severe bradycardia during cerebral aneurysm clipping surgery by topical anesthesia of the dura surface and atropine administration: a case report

Background Trigeminocardiac reflex (TCR) by stimulation of the sensory branch of the trigeminal nerve induces transient bradycardia and hypotension. We report a case in which light mechanical stimulation to the dura mater during brain surgery induced severe bradycardia. Case presentation A 77-year-old woman with bradycardia-tachycardia syndrome was scheduled for clipping of an unruptured left middle cerebral artery aneurysm. General anesthesia was performed with propofol, remifentanil, and rocuronium. Before starting surgery, the function of the pyramidal tract was examined by motor evoked potential. Transcranial electric stimulation for motor evoked potential induced atrial fibrillation and tachycardia. Continuous administration of landiolol was started and verapamil was used for tachycardia. During detachment of the dura mater from the bone, an electrocardiogram suddenly showed sinus arrest for 6 s. Immediately after the manipulation was interrupted, a junctional rhythm appeared. However, light touch to the dura mater induced severe bradycardia again, and atropine was therefore administered. In addition, the dura surface was anesthetized with topical lidocaine infiltration. After that, light touch-induced bradycardia was prevented. Conclusions We experienced a case of severe bradycardia during surgery due to TCR caused by light mechanical stimulation to the dura mater. Topical anesthesia of the dura surface and atropine administration were effective for preventing TCR-induced bradycardia.

Analgesic activity of Phong Thap Dan tablets in animal models

Phong thap dan tablets are intended to treat low back pain. This study was carried out to evaluate theanalgesic effects of Phong thap dan tablets in experimental animals. The analgesic effects were evaluated inthree animal models: hot plate, mechanical stimulation and acetic acid-induced writhing test. Mice were dividedinto 4 groups given oral water, control drug (codein phosphate in hot plate and mechanical stimulation tests oraspirin in writhing test), Phong thap dan at 2.88 tablets (1.44 g) or 8.64 tablets (4.32 g)/kg b.w/day, respectively.Our results showed that Phong thap dan tablets at both doses increased the reaction time to thermal stimulation,increased the paw withdrawal latency and the force required to elicit a paw withdrawal and decreased thenumber of acetic acid-induced writhing movements in mice. There was no statistically significant differencebetween 2 doses of Phong thap dan tablets in three animal models. We conclude that Phong thap dan tabletsat the doses of 2.88 tablets and 8.64 tablets/kg b.w/day showed significant analgesic effect in animal models.

Early mechanical stimulation of the nipple-areola receptors complex promotes the mammary milk ejection function in women delivered by cesarean section

Mechanical stimulation and milk ejection from mammary gland in women delivered by caesarean section since 1 day post partum by the breastpump with vacuum and compression stimuli promotes milk ejection function. On the third day postpartum the stimulated mothers had significantly more milk flow reflex peaks than those who were not subjected to stimulation during the 10 min milk ejection session.

Characterization of increased mucus production of HT29-MTX-E12 cells grown under Semi-Wet interface with Mechanical Stimulation

The intestinal mucus layer plays a crucial role in human health. To study intestinal mucus function and structure in vitro, the mucus-producing intestinal cell line HT29-MTX-E12 has been commonly used. However, this cell line produces only low amounts of the intestine-specific MUC2. It has been shown previously that HT29-MTX-E12 cells cultured under Semi-Wet interface with Mechanical Stimulation (SWMS) produced higher amounts of MUC2, concomitant with a thicker mucus layer, compared to cells cultured conventionally. However, it remains unknown which underlying pathways are involved. Therefore, we aimed to further explore the cellular processes underlying the increased MUC2 production by HT29-MTX-E12 cells grown under SWMS conditions. Cells grown on Transwell membranes for 14 days under static and SWMS conditions (after cell seeding and attachment) were subjected to transcriptome analysis to investigate underlying molecular pathways at gene expression level. Caco-2 and LS174T cell lines were included as references. We characterized how SWMS conditions affected HT29-MTX-E12 cells in terms of epithelial barrier integrity, by measuring transepithelial electrical resistance, and cell metabolism, by monitoring pH and lactate production per molecule glucose of the conditioned medium. We confirmed higher MUC2 production under SWMS conditions at gene and protein level and demonstrated that this culturing method primarily stimulated cell growth. In addition, we also found evidence for a more aerobic cell metabolism under SWMS, as shown previously for similar models. In summary, we suggest different mechanisms by which MUC2 production is enhanced under SWMS and propose potential applications of this model in future studies.

Round Window Stimulation of the Cochlea

Mixed hearing loss associated with a sensorineural component and an impaired conductive mechanism for sound from the external ear canal to the cochlea represents a challenge for rehabilitation using either surgery or traditional hearing amplification. Direct stimulations of the ossicular chain and the round window (RW) membrane have allowed an improved hearing in this population. The authors review the developments in basic and clinical research that have allowed the exploration of new routes for inner ear stimulation. Similar changes occur in the electrophysiological measures in response to auditory stimulation through the traditional route and direct mechanical stimulation of the RW. The latter has proven to be very effective as a means of hearing rehabilitation in a group of patients with significant difficulties with hearing and communication.