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Biomedical subjects

Jens Ellrich

Publications and source records attributed to Jens Ellrich.

At least 19 recordsLinked to original sources

Impaired thermal perception in cluster headache.

Cluster headache is characterized by attacks of severe periorbital pain. Repetitive burst activity in afferent fibers may induce plastic alterations in somatosensory synaptic processing as a prerequisite for recurring and chronic pain. This psychophysical study addressed hypothesized dysfunctions in craniofacial somatosensory processing in cluster headache disease. Thermal and mechanical sensory functions in the periorbital region were assessed by quantitative sensory testing (QST) in 25 cluster headache patients and 60 healthy volunteers. Perception of warmth (p<0.01), cold (p<0.000001), and pressure pain (p<0.05) was reduced on the cluster side as compared with the contralateral asymptomatic side. In contrast to healthy volunteers, warm detection threshold (WDT) and thermal sensory limen (TSL) on one side did not positively correlate with the other side. WDT and TSL negatively correlated with the elapsed time since last attack. All patients showed QST abnormalities on the headache side in comparison to healthy controls. Loss of sensory functions strongly preponderated gain. Several lines of evidence indicate a pivotal role of the hypothalamus in cluster headache pathophysiology. The impairment of warm and cold perception in patients may be based upon a dysfunction of the hypothalamus which is strongly involved in thermosensory control.

Adult↗

Heterosynaptic long-term depression of craniofacial nociception: divergent effects on pain perception and blink reflex in man.

Noxious low-frequency stimulation (LFS) of presynaptic nerve fibers induces long-term depression (LTD) of synaptic transmission. In vitro studies suggest a sole homosynaptic effect. Consequently, the present study addressed the hypothesis that LTD of craniofacial nociception in man is mediated by a homosynaptic mechanism. Nociceptive supraorbital afferents were excited by electric pulses via a concentric electrode in ten healthy volunteers. The electrically evoked bilateral blink reflex (BR) was recorded from both orbicularis oculi muscles by surface electrodes. The BR was evoked in blocks of ten electric stimuli each (0.1 Hz) with an interblock interval of 8 min. Conditioning noxious LFS (1 Hz, 20 min) was applied via concentric electrode either to the same site as BR test stimuli (ipsilateral) or to the corresponding contralateral forehead area (contralateral). LFS and test stimulus intensities corresponded to about threefold the pain threshold. After three baseline stimulus blocks, either conditioning ipsilateral or contralateral LFS were applied or stimulation was interrupted for 20 min as a control task. Afterwards, test stimulation blocks were continued for 40 min. Each volunteer participated in all three sessions on different days. Noxious LFS induced LTD of the BR independently from the side of conditioning stimulation. Pain perception decreased after ipsilateral LFS but not after contralateral LFS. The bilateral effect of noxious LFS on the BR provides evidence for heterosynaptic LTD based on bilateral projections of supraorbital nerve afferents onto spinal trigeminal nuclei. The divergent effect on pain perception may be due to a preferential contralateral projection of nociceptive afferents onto reflex interneurons but not onto trigeminothalamic projection neurons.

Adult↗

Dopamine D2-like receptor activation antagonizes long-term depression of orofacial sensorimotor processing in anesthetized mice.

Long-term depression (LTD) of orofacial sensorimotor processing recently has been demonstrated in anesthetized mice. Due to the remarkable role of dopamine in central nervous system LTD, the influence of dopamine D2 receptor activation on LTD of the jaw-opening reflex (JOR) was investigated. Electric low-frequency stimulation (LFS, 1 Hz) of the tongue suppressed the JOR integral by 43% for at least 1 h. After systemic administration of the dopamine D2-like receptor agonist quinpirole, LTD was significantly attenuated to 14%. JOR decreased for only about 15 min after LFS according to a short-term depression. Under systemic application of the dopamine D2-like receptor antagonist sulpiride, LTD significantly increased to 64%, again for at least 1 h. Thus, D2-like receptor activation prevented LTD, and D2-like receptor blockade amplified LTD of the reflex. The time course of inhibition may be due to a dopaminergic D2-like receptor mechanism that antagonizes the transfer from short-term into long-term depression. Considering a putative mediation of LTD by the endogenous pain control system, the results correspond to the known inhibitory control of this system by a D2-like receptor mechanism.

Analysis of Variance↗

Neurophysiological monitoring of alveolar nerve function during sensor-controlled Er:YAG laser corticotomy in rabbits.

BACKGROUND AND OBJECTIVES: The sensor-controlled Er:YAG laser system may be a potent tool for tissue specific cutting in surgery. In order to investigate the impact of the laser on neural tissues, inferior alveolar nerve (IAN) function was monitored by the jaw-opening reflex (JOR) during specific corticotomy in rabbits. STUDY DESIGN/MATERIALS AND METHODS: Laser jaw corticotomy was performed in 13 anesthetized rabbits. During and after specific corticotomy the JOR was evoked by electric intraoral stimulation to monitor effects on IAN function. RESULTS: The JOR permanently abolished in one case and transiently failed immediately after surgery but largely recovered within days in another rabbit. In one experiment JOR threshold increased 7 days after corticotomy. Histology did not prove any objective nerve pathology. CONCLUSIONS: Monitoring IAN function by the JOR demonstrated the relatively low risk of nerve damaging during sensor-controlled laser corticotomy.

Animals↗

Nerve growth factor injection into semispinal neck muscle evokes sustained facilitation of the jaw-opening reflex in anesthetized mice -- possible implications for tension-type headache.

Nociceptive input from neck muscles probably plays a role in the pathophysiology of tension-type headache. In order to elaborate an animal model, the impact of noxious input from neck muscles on orofacial sensorimotor processing was investigated by electrophysiological means in anesthetized mice. Group IV muscle afferents of the semispinal neck muscle were excited by local injection of nerve growth factor (NGF, 0.8 microM, 20 microl). Orofacial sensorimotor processing was monitored by the jaw-opening reflex (JOR) elicited by electric tongue stimulation. After unilateral NGF injection into the right neck muscle (n = 10), JOR integral (+89%) and duration (+9%) increased and latency decreased (-5%) for at least 1 h. Bilateral injection of NGF (n = 10) into neck muscles induced an increase of JOR integral (+111%) and duration (+20%) and a reduction of latency (-9%). This facilitation of the JOR lasted for at least 90 min without any downward drift (n = 5). Electric JOR threshold diminished after NGF injection. After intramuscular injection of isotonic saline into the right semispinal neck muscle (20 microl), the JOR remained unchanged (n = 10). Local NGF injection into neck muscles evoked noxious input to the brainstem that induced a sustained central facilitation of the JOR for more than 1 h. This long-term facilitation of orofacial sensorimotor processing by a singular NGF injection possibly reflects plastic changes of nociceptive synaptic processing that may be involved in the pathophysiology of headache.

Anesthesia↗

Electric low-frequency stimulation of the tongue induces long-term depression of the jaw-opening reflex in anesthetized mice.

Long-term depression (LTD) of somatosensory processing has been demonstrated in slice preparations of the spinal dorsal horn. Although LTD could be reliably induced in vitro, inconsistent results were encountered when the same types of experiments were conducted in adult animals in vivo. We addressed the hypothesis that LTD of orofacial sensorimotor processing can be induced in mice under general anesthesia. The effects of electric low- and high-frequency conditioning stimulation of the tongue on the sensorimotor jaw-opening reflex (JOR) elicited by electric tongue stimulation were investigated. Low-frequency stimulation induced a sustained decrease of the reflex integral for >/=1 h after the end of conditioning stimulation. After additional high-frequency stimulation, the reflex partly recovered from LTD. High-frequency stimulation alone induced a transient increase of the JOR integral for <10 min. The LTD of the sensorimotor jaw-opening reflex in anesthetized mice may be an appropriate model to investigate the central mechanisms and the pharmacology of synaptic plasticity in the orofacial region. The application of electrophysiological techniques in mice provides the opportunity to include adequate knock-out models to elucidate the neurobiology of LTD.

Anesthesia↗

Low-frequency stimulation of trigeminal afferents induces long-term depression of human sensory processing.

Electric low-frequency stimulation (LFS) of afferent nerve fibers reliably induces long-term depression (LTD) of synaptic transmission in vitro. LTD is suggested to be one important mechanism of synaptic plasticity in the mammalian brain. The study demonstrated an LTD of evoked cortical potentials (-30%) and perception ratings (-25%) by noxious electric LFS of trigeminal afferents in man, indicating that LTD may also be involved in human synaptic plasticity.

Adult↗

Effects of acetylsalicylic acid and morphine on neurons of the rostral ventromedial medulla in rat.

Morphine exerts its analgesic effect via the endogenous pain control system consisting of the periaqueductal grey (PAG) and the rostral ventromedial medulla (RVM). Acetylsalicylic acid (ASA) may also act via this system, but so far this has only been demonstrated for the inhibitory effect on the tail-flick reflex with extremely high doses (200-300 mg/kg). Both drugs show synergistic effects on PAG neurons in vitro. It is unclear whether this mechanism accounts for the well-known analgesic synergism of these drugs in vivo. Thus, the effects of ASA (30 mg/kg) and morphine on off- and on-cells in the RVM and the jaw-opening reflex (JOR) were investigated in anesthetized rats. Under morphine, off-cell activity increased (+34%), on-cell activity decreased (-98%) and the reflex was suppressed (-53%). ASA increased off-cell activity (+20%) and decreased the activity of on-cells (-52%). After preceding ASA administration, the effects of morphine on off- and on-cells and on the reflex did not alter statistically. The experiments document the modulatory effect of a clinically relevant dose of ASA on RVM cells. This effect resembles that of morphine. The results do not support the hypothesis of a mediation of the analgesic synergism of morphine and ASA by the PAG-RVM-network in vivo.

Analgesics, Opioid↗

Electrophysiology of sensory and sensorimotor processing in mice under general anesthesia.

Like many other complex biological phenomena, sensory processing is starting to be studied at the level of the gene. Whereas the mouse is the standard organism for molecular neurobiology, somatosensation and pain are mainly investigated in the rat. The in-vitro electrophysiological technique is well established in mice. The effect of manipulations of the mouse genome on neuronal systems and networks has to be investigated under in-vivo conditions. Thus, the step from the rat to the smaller mouse seems to be important in terms of progress in molecular neurobiology. So far, there is no published study of sensory processing by electrophysiological means in mice under controlled general anesthesia. In this paper we describe a technique for electrophysiological recordings of sensory and sensorimotor processing in anesthetized mice. The mouse is anesthetized by continuous administration of the short-acting general anesthetic methohexital sodium salt via the jugular vein and artificially ventilated via a tracheotomy. The electrocardiogram and the carotid artery blood pressure are monitored. The sensorimotor jaw-opening reflex and the hindpaw withdrawal reflex are elicited by electric stimulation of the tongue and the sole of the hindpaw, respectively. The jaw-opening reflex is inhibited by deep brain stimulation of the rostral ventromedial medulla. On- and off-cells of the rostral ventromedial medulla and sensory neurons of the spinal trigeminal nucleus are extracellularly recorded by tungsten electrodes. General anesthesia can be reliably induced, maintained and sufficiently controlled in mice. Under this condition, studies can be performed on sensory processing in mice.

Action Potentials↗

Long-term depression of the human blink reflex.

Long-term depression (LTD) of synaptic transmission is reliably induced by low-frequency stimulation (LFS) of presynaptic nerve fibers in vitro. Many experiments suggest that LTD of basal transmission is not readily induced either in awake or anesthetized animals in vivo. In order to fill the gap between the in vitro cell studies and the in vivo situation, the effect of LFS on trigeminal somatosensory processing in healthy volunteers was investigated. Excitability of trigeminal sensory neurons was tested by applying the blink reflex (BR) elicited by electric stimulation of supraorbital nerve afferents. LFS of these afferents induced a significant reduction of the BR integral, a significant increase of the BR onset latency and a significant decrease of the stimulus intensity ratings. This depressive effect on the BR lasted for at least 1 h after the end of LFS. Thus, this study documented for the first time a long-term depression of trigeminal somatosensory processing in healthy volunteers.

Adult↗

Long-term depression of the human masseter inhibitory reflex.

Long-term depression (LTD) of synaptic transmission is reliably induced by low-frequency stimulation (LFS) of nociceptive afferents in vitro. LTD can only exceptionally be induced in anesthetized animals. In order to fill the gap between the in vitro cell studies and the in vivo situation, the effects of LFS on the masseter inhibitory reflex (MIR) were investigated in man. Noxious LFS of mental nerve afferents caused a significant depression of the early MIR1 and the late MIR2 components. Whereas the onset latency (+25%), the duration (-42%) and the integral (+68%) of the MIR2 were strongly modulated after LFS, only the integral (+35%) of the MIR1 significantly changed. The results document a long-term depression of trigeminal somatosensory processing in man. The different effects of LFS on the two components of the MIR may point to central mechanisms of LTD.

Adult↗

Atypical on-, off- and neutral cells in the rostral ventromedial medulla oblongata in rat.

It is generally assumed that the response pattern of on-, off- and neutral cells in the rostral ventromedial medulla (RVM) to noxious stimulation is independent of stimulation site. But recent studies have shown that a remarkable number of RVM neurons do not have whole-body receptive fields. These so-called atypical neurons were extracellularly recorded in lightly anaesthetized rats. The receptive fields to noxious thermal and mechanical stimulation applied to the tail, the extremities and the craniofacial region were determined in 57 RVM neurons. In 24 atypical off-cells, 12 on-cells and 21 neutral cells, the response pattern evoked by noxious pinch to the nose, forehead and ear most frequently differed from the responses to noxious tail heat. The modulatory effects of intravenously administered morphine were examined in 21 cells. In contrast to the general assumption that morphine activates off-cells, inhibits on-cells and has no effect on neutral cells, in atypical RVM neurons 5 of 6 off-cells, 2 of 6 on-cells and 5 out 9 neutral cells showed a different response pattern to systemical administration of morphine. The results show that a RVM cell classification that is exclusively based on the behaviour to noxious tail heat can neither sufficiently predict the response pattern to different noxious stimuli, especially in the craniofacial region, nor reliably predict the modulatory effect of morphine in RVM neurons. The fact that the neutral cells responded in an off or on manner to noxious stimulation different from noxious tail heat and that morphine modulated activity in many neutral cells suggests that these cells are probably subtypes of on- and off-cells.

Action Potentials↗

Modulation of neuronal activity in the nucleus raphé magnus by the 5-HT(1)-receptor agonist naratriptan in rat.

Modulatory effects of the new antimigraine drug naratriptan, a 5-HT(1)-receptor-agonist, on neurons of the nucleus raphé magnus were examined in rat by extracellular recordings. In the nucleus raphé magnus neuronal activity decreased in on-cells and increased in off-cells after intravenous administration of naratriptan. The modulatory effects of naratriptan were similar to the well-known effects of morphine on neurons in the nucleus raphé magnus. The results of this study suggest central actions of naratriptan and may point to an involvement of the endogenous pain control system in the antinociceptive effects of the 5-HT(1)-receptor-agonist.

Animals↗

Is the R3 component of the human blink reflex nociceptive in origin?

The R3 component of the blink reflex can reproducibly be evoked by noxious stimulation but can probably also be elicited by innocuous stimuli. This study was conducted to investigate the contribution of nociceptive A delta and C fibers to the generation of the electrically evoked R3 blink reflex. Electrical thresholds for detection, pain and all blink reflex components were determined and the modulatory effects of local anesthesia were investigated. The electrical R3 threshold of 4.6 +/- 0.5 mA (mean +/- SE) corresponded to 2.9 times the detection threshold and to 0.35 times the pain threshold. The R3 threshold was significantly below the pain threshold. Under local anesthesia of the supraorbital skin with a complete loss of warm and cold sensation, a loss of pinprick sensation, but a normal detection of tactile stimuli, the electrical pain threshold increased, all other thresholds remained unchanged. Under local anesthesia none of the reflex components were significantly reduced. Cutaneous A beta fibers and nociceptive A delta fibers, but not unmyelinated C fibers, contribute to the generation of the electrically evoked R3 component. According to the recruitment order in peripheral sensory nerves the electrical threshold of the R3 is mainly determined by activation of A beta fibers. Thus, it can not be assumed that the electrically evoked R3 is an adequate model to investigate nociceptive processing.

Adult↗

Brain Stem Reflexes: Probing Human Trigeminal Nociception.

Although many people suffer from orofacial pain and headache, objective methods for investigation of trigeminal nociception in humans have been lacking. Trigeminal brainstem reflexes such as the masseter inhibitory reflex and the blink reflex are mediated by central multireceptive neurons that are also involved in trigeminal nociception. Therefore, these trigeminal reflexes are suitable models for probing pontine and medullary pain processing.

Journal Article↗

C- and A delta-fiber components of heat-evoked cerebral potentials in healthy human subjects.

Feedback-controlled laser heat was used to stimulate the hairy skin of the hand dorsum and forearm, and heat-evoked cerebral potentials were recorded at midline (Fz, Cz, Pz) and temporal (T3, T4) scalp positions. Based on data from primary afferent electrophysiology a stimulus level (40 degrees C) was chosen, which is above C-fiber heat threshold, but clearly below A delta-nociceptor heat threshold in order to excite selectively C-fibers without concomitant excitation of A delta-fibers. Feedback-controlled stepped heat stimuli to 40 degrees C elicited ultralate laser evoked potentials (LEPs) at the vertex in a high proportion of experiments (90%). Estimates of conduction velocity calculated from latency shifts between the hand and forearm sites of ultralate LEPs (2.4 m/s) and of reaction times (2.8 m/s) confirmed mediation of ultralate potentials by unmyelinated nerve fibers (nociceptors and/or warm fibers). The ultralate LEP could be differentiated from resolution of contingent negative variation (CNV), an endogenous potential related to expectation and response preparation, by its scalp topography. Strong heat stimuli of 48 degrees C, which is suprathreshold for most A delta- and C-fiber nociceptors, elicited the well-known late LEPs mediated by nociceptive Adelta-fibers confirming previous studies. The LEP waveform to strong heat stimuli also contained an ultralate component reminiscent of an ultralate LEP following the late LEP. Ultralate and late LEP had identical scalp topography. In conclusion, the method of temperature-controlled laser heat stimuli allows the selective and reliable examination of A delta- and C-fiber-mediated afferent pathways and the related cortical processing without the complication of dissociating A-fiber nerve blocks.

Adult↗