Distinct roles of ASIC3 and TRPV1 receptors in electroacupuncture-induced segmental and systemic analgesia

Previous studies have demonstrated the effects of different afferent fibers on electroacupuncture (EA)-induced analgesia. However, contributions of functional receptors expressed on afferent fibers to the EA analgesia remain unclear. This study investigates the roles of acid-sensing ion channel 3 (ASIC3) and transient receptor potential vanilloid 1 (TRPV1) receptors in EA-induced segmental and systemic analgesia. Effects of EA at acupoint ST36 with different intensities on the C-fiber reflex and mechanical and thermal pain thresholds were measured among the ASIC3^−/−, TRPV1^−/−, and C57BL/6 mice. Compared with C57BL/6 mice, the ipsilateral inhibition of EA with 0.8 C-fiber threshold (0.8Tc) intensity on C-fiber reflex was markedly reduced in ASIC3^−/− mice, whereas the bilateral inhibition of 1.0 and 2.0Tc EA was significantly decreased in TRPV1^−/− mice. The segmental increase in pain thresholds induced by 0.3 mA EA was significantly reduced in ASIC3^−/− mice, whereas the systemic enhancement of 1.0 mA EA was markedly decreased in TRPV1^−/− mice. Thus, segmental analgesia of EA with lower intensity is partially mediated by ASIC3 receptor on Aβ-fiber, whereas systemic analgesia induced by EA with higher intensity is more likely induced by TRPV1 receptor on Ad- and C-fibers.     

Sensory processing during kinesthetic aftereffect following illusory hand movement elicited by tendon vibration

We investigated how the human sensory-motor system elicits a somatosensory aftereffect. Tendon vibration of a limb excites the muscle spindle afferents that contribute to eliciting illusory movements of the limb. After the cessation of vibration, a transient sensation in which the vibrated limb returns towards its original position (kinesthetic aftereffect) is often experienced, even in the absence of the afferent inputs recruited by the vibration. We vibrated the tendon of either the right wrist extensor or flexor muscle that elicited an illusory flexion or extension movement, which was followed by its corresponding extension or flexion aftereffect. First, we psychophysically investigated how the preceding illusory movement affects the aftereffect. Second, we examined the cortico-spinal excitability during the aftereffect to evaluate its changes from the time during the illusion. We measured the amplitude of the motor-evoked potential that is evoked by a single-pulse transcranial magnetic stimulation to the hand section of the contralateral motor cortex (M1). All 19 subjects experienced the aftereffect, and the amount of aftereffect was approximately 70% of the preceding illusion. During the illusion, the cortico-spinal excitability increased more in non-vibrated than in vibrated muscle, so as to reflect the illusory directions. During the aftereffect, the excitability was significantly reduced only in the non-vibrated muscle, with no change in the vibrated muscle, which, in turn, caused an opposite pattern in the unbalanced excitability between the two muscles, and the degree of unbalanced excitability was correlated with the sensation of aftereffect. The kinesthetic aftereffect seems to be elicited by a sensory process that is determined by the preceding illusory movements. Motor-cortical processing of the unbalanced sensory information from the stimulated and non-stimulated muscles may contribute to the elicitation of kinesthetic aftereffect.     

Mice without transcription factor KLF7 provide new insight into olfactory bulb development

Recent genetic studies have excluded that peripheral innervation plays a substantial role in the initial outgrowth of the olfactory bulb. Mice without Kruppel-like factor 7 activity die at birth and display hypoplastic olfactory bulbs which lack peripheral innervation. Here, we report that incomplete penetrance of the mutation is responsible for partial bulb innervation in a small fraction of Klf7 null mice. Analysis of the partially innervated bulbs of mutant embryos, newborns and adult mice revealed an obligatory correlation with local restoration of laminar architecture, neuronal cell differentiation and neuronal activity. The degree of normal OB maturation in Klf7-/- OBs was proportional to the degree of peripheral innervation. These findings therefore indicate that peripheral innervation contributes to bulb maturation late in development by promoting cell morphogenesis and differentiation.     

Improved organotypic cell culture model for analysis of the neuronal circuit involved in the monosynaptic stretch reflex

Knowledge regarding neuronal circuit formation is central for the understanding of the vast network making up the brain. It is therefore necessary to find novel ways to analyze the mechanisms involved in well-defined neural circuits. We present an improved in vitro model of the monosynaptic stretch reflex circuit, based on primary organotypic cell cultures. By using limb tissue as a source of muscle fibers instead of circumspinal tissue we could make the in vitro system more in vivo like in the sense that it focuses on the stretch reflex involving limb muscles. Furthermore, our analyses showed that this procedure allows muscle fibers to follow the normal developmental pattern. Particularly interesting was the finding of slow tonic myosin heavy chain expressing muscle fibers, a developmental marker for muscle spindles, in the cultures showing that this system has the potential to contain the complete reflex circuits.     

The effect of intravenously administered mexiletine on tinnitus-a pilot study

The effect of intravenously administered mexiletine on subjective tinnitus and hearing was studied in six patients, who initially responded positively to lidocaine. Distinct mexiletine-induced decreases in tinnitus loudness were demonstrated in three subjects, as reflected by maximum VAS (visual analogue scale) level reduction of 34%, 95%, and 100%, respectively. One subject reported change in tinnitus pitch, another one showed a slight (18% on VAS) tinnitus reduction, and one subject disclosed no effect. Side effects were seen only during one of seven infusions. Mexiletine induced shifts in pure-tone threshold, transient evoked otoacoustic emission, and acoustic reflex threshold, probably reflecting a reversible interference in the function of organ of Corti. The concentration effect relationship remained unclear and no general ‘therapeutic’ level could be identified. This study confirms the effect of mexiletine on the auditory function and its potential as a possible therapeutic agent or a model for further development in tinnitus pharmacotherapy.     

Latency of the jaw-opening reflex in the premature, preweaning and adolescent pig (hanford strain miniature pig, Sus scrofa)

The jaw-opening (digastric) reflex was elicited by electrical stimulation of oral mucosa in miniature pigs (Sus scrofa) varying in age from 5 days premature to 101 days post-term. The latency of reflex electromyographic activity varied between 12–14 ms in the most immature animals and 9–11 ms in the oldest animals. The very long-latency digastric responses found in the immature young of nesting mammals were not seen in the relatively precocious young of this species.     

Anticipatory and reflexive neck muscle activities during voluntary rapid jaw opening and passive jaw depression in humans

The characteristics of head movement during voluntary rapid jaw opening movement and passive jaw depression were investigated using accelerometers and electromyographs (EMG) on eight healthy examinees. Passive depressions were executed by means of load on the lower jaw, initiated either by examinees themselves or an experimenter. In the depression initiated by examinees, a head-extension movement that preceded the load to the lower jaw and anticipatory activities in the nuchal region of the trapezius muscle were observed. In the depression initiated by the experimenter, the anticipatory activities were not observed. In both of these cases, stretch reflexes were induced in the trapezius muscle. During voluntary rapid jaw opening, a head-extension movement nearly synchronized with the opening movement in the lower jaw acceleration, and dorsal-neck muscle activities accompanying the synchronized movement were observed. The peak timing of these neck-muscle activities preceded the latencies of the stretch-reflex activities observed in the jaw-depressed tasks, but no anticipatory activities were observed in the dorsal-neck muscles. We conclude that neither the anticipatory activities nor the reflex activities observed in the passive depressions have effects on the initial part of the dorsal-neck muscle activities, which are related to the head-extension synchronized with the voluntary lower-jaw opening movement.     

Three-Dimensional Vibration-Induced Vestibulo-ocular Reflex Identifies Vertical Semicircular Canal Dehiscence

Vertical semicircular canal dehiscence (VSCD) due to superior canal dehiscence (SCD) or posterior canal dehiscence (PCD) of the temporal bone causes vestibular and cochlear hypersensitivity to sound. This study aimed to characterize the vibration-induced vestibulo-ocular reflex (ViVOR) in VSCD. ViVORs in one PCD and 17 SCD patients, confirmed by CT imaging reformatted in semicircular canal planes, were measured with dual-search coils as binocular three-dimensional eye rotations induced by skull vibrations from a bone oscillator (B71—10 ohms) at 7 ms, 500 Hz, 135-dB peak-force level (re: 1 μN). The ViVOR eye rotation axes were computed by vector analysis and referenced to known semicircular canal planes. Onset latency of the ViVOR was 11 ms. ViVOR from VSCD was up to nine times greater than normal. The ViVOR’s torsional rotation was always contraversive-torsional (the eye’s upper pole rotated away from the stimulated ear), i.e. its direction was clockwise from a left and counterclockwise from a right VSCD, thereby lateralizing the side of the VSCD. The ViVORs vertical component distinguishes PCD from SCD, being downwards in PCD and upwards in SCD. In unilateral VSCD, the ViVOR eye rotation axis aligned closest to the dehiscent vertical semicircular canal axis from either ipsilateral or contralateral mastoid vibrations. However, in bilateral VSCDs, the ViVOR eye rotation axis lateralized to the ipsilateral dehiscent vertical semicircular canal axis. ViVOR was evoked in ossicular chain dysfunction, even when air-conducted click vestibulo-ocular reflex (VOR) was absent or markedly reduced. Hence, ViVOR could be a useful measurement to identify unilateral or bilateral VSCD even in the presence of ossicular chain dysfunction.     

Fixed drug eruption:state of the art

Fixed drug eruption (FDE) is a common type of cutaneous adverse drug reaction.There may be a genetic background as significant associations have been identified between HLA types and specific FDE.Systemic provocation is still the gold standard for establishing the offending agent in FDE,but topical provocation testing offers a promising alternative approach. A standardized method does not exist, and the approach must likely be varied for different agents. The mystery of site preference in FDE is still unresolved. Possible explanations include properties of the drug, trauma and viscerocutaneous reflex patterns.