Quantitative assessment of the nociceptive withdrawal reflex in healthy, non-medicated experimental sheep

This study aimed to characterize the nociceptive withdrawal reflex (NWR) and to define the nociceptive threshold in 25 healthy, non-medicated experimental sheep in standing posture. Electrical stimulation of the dorsal lateral digital nerves of the right thoracic and the pelvic limb was performed and surface-electromyography (EMG) from the deltoid (all animals) and the femoral biceps (18 animals) or the peroneus tertius muscles (7 animals) was recorded. The behavioural reaction following each stimulation was scored on a scale from 0 (no reaction) to 5 (strong whole body reaction). A train-of-five 1 ms constant-current pulse was used and current intensity was stepwise increased until NWR threshold intensity was reached. The NWR threshold intensity (It) was defined as the minimal stimulus intensity able to evoke a reflex with a minimal Root-Mean-Square amplitude (RMSA) of 20 μV, a minimal duration of 10 ms and a minimal reaction score of 1 (slight muscle contraction of the stimulated limb) within the time window of 20 to 130 ms post-stimulation. Based on this value, further stimulations were performed below (0.9It) and above threshold (1.5It and 2It). The stimulus-response curve was described. Data are reported as medians and interquartile ranges. At the deltoid muscle It was 4.4 mA (2.9–5.7) with an RMSA of 62 μV (30–102). At the biceps femoris muscle It was 7.0 mA (4.0–10.0) with an RMSA of 43 μV (34–50) and at the peroneus tertius muscle It was 3.4 mA (3.1–4.4) with an RMSA of 38 μV (32–46). Above threshold, RMSA was significantly increased at all muscles. Below threshold, RMSA was only significantly smaller than at It for the peroneus tertius muscle but not for the other muscles.

Anatomical organization of the memory underlying sensitization in the siphon-withdrawal reflex circuit of {\it Aplysia californica}

Previous studies have shown that short-term sensitization of the Aplysia siphon-withdrawal reflex circuit results in multiple sites of change in synaptic efficacy. In this dissertation I have used a realistic modeling approach (using an integrate-and-fire scheme), in conjunction with electrophysiological experiments, to evaluate the contribution of each site of plasticity to the sensitized response.^ This dissertation contains a detailed description of methodology for the construction of the model circuit, consisting of the LFS motor neurons and ten interneurons known to convey excitatory input to them. The model replicates closely the natural motor neuron firing response to a brief tactile stimulus.^ The various circuit elements have different roles for producing circuit output. For example, the sensory connections onto the motor neuron are important for the production of the phasic response, while the polysynaptic interneuronal connections are important for producing the tonic response.^ The multiple sites of plasticity that produce changes in circuit output also have specialized roles. Presynaptic facilitation of the sensory neuron to LFS connection enhances only the phasic component of the motor neuron firing response. The sensory neuron to interneuron connections primarily enhance the tonic component of the motor neuron firing response. Also, the L29 posttetanic potentiation and the L30 presynaptic inhibition primarily enhance the tonic component of the motor neuron firing response. Finally, the information content at the various sites of plasticity can shift with changes in stimulus intensity. This suggests that while the sites of plasticity encoding memory are fixed, the information content at these sites can be dynamic, shifting in anatomical location with changes in the intensity of the test stimulus.^ These sites of plasticity also produce specific changes in the behavioral response. Sensory-LFS plasticity selectively increases the amplitude of the behavioral response, and has no effect on the duration of the behavioral response. Interneuronal plasticity (L29 and L30) affects both the amplitude and duration of the behavioral response. Other sensory plasticity also affect both the amplitude and duration of the behavioral response, presumably by increasing the recruitment of the interneurons, which provide all of the effect on duration of the behavioral response. ^

Accuracy of the withdrawal reflex for localization of the site of cervical disk herniation in dogs: 35 cases (2004-2007)

OBJECTIVE To evaluate the accuracy of neurologic examination versus magnetic resonance imaging (MRI) in localization of cervical disk herniation and evaluate the usefulness of withdrawal reflex testing in dogs. DESIGN Retrospective case series. ANIMALS 35 client-owned dogs with a single-level cervical disk herniation as determined via MRI. PROCEDURES 1 of 2 board-certified neurologists performed a complete neurologic examination in each dog. Clinical signs of a cervical lesion included evidence of neck pain and tetraparesis. The withdrawal reflex was used for neuroanatomic localization (C1-C5 or C6-T2). Agreement between results of neurologic and MRI examinations was determined. RESULTS Agreement between neurologic and MRI diagnoses was 65.8%. In 11 dogs in which the lesion was clinically localized to the C6-T2 segment on the basis of a decreased withdrawal reflex in the forelimbs, MRI revealed an isolated C1-C5 disk lesion. In 1 dog, in which the lesion was suspected to be at the C1-C5 level, MRI revealed a C6-T2 lesion. Cranial cervical lesions were significantly associated with an incorrect neurologic diagnosis regarding site of the lesion. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that the withdrawal reflex in dogs with cervical disk herniation is not reliable for determining the affected site and that a decreased withdrawal reflex does not always indicate a lesion from C6 to T2.

Antinociceptive effect of buprenorphine and evaluation of the nociceptive withdrawal reflex in foals.

OBJECTIVE To elicit and evaluate the NWR (nociceptive withdrawal reflex) in 2 and 11 day old foals, to investigate if buprenorphine causes antinociception and determine if the NWR response changes with increasing age. The effect of buprenorphine on behaviour was also evaluated. STUDY DESIGN Prospective, experimental cross-over trial. ANIMALS Nine Norwegian Fjord research foals. METHODS Buprenorphine, 10 μg kg(-1) was administered intramuscularly (IM) to the same foal at 2 days and at 11 days of age. The NWR and the effect of buprenorphine were evaluated by electromyograms recorded from the left deltoid muscle following electrical stimulation of the left lateral palmar nerve at the level of the pastern. Mentation, locomotor activity and respiratory rate were recorded before and after buprenorphine administration. RESULTS We were able to evoke the NWR and temporal summation in foals using this model. Buprenorphine decreased the root mean square amplitude following single electrical stimulation (p < 0.001) in both age groups, and increased the NWR threshold following single electrical stimulation in 2 day old foals (p = 0.0012). Repeated electrical stimulation at 2 Hz was more effective to elicit temporal summation compared to 5 Hz (p < 0.001). No effect of age upon the NWR threshold was found (p = 0.34). Sedation when left undisturbed (11 occasions), increased locomotor activity when handled (9 occasions) and tachypnea (13 occasions) were common side-effects of buprenorphine. CONCLUSION AND CLINICAL RELEVANCE These findings indicate that buprenorphine has antinociceptive effect in foals. Opioid side effects often recognized in adult horses also occur in foals.

Is the conditioned pain modulation paradigm reliable? A test-retest assessment using the nociceptive withdrawal reflex.

The aim of this study was to determine the reliability of the conditioned pain modulation (CPM) paradigm assessed by an objective electrophysiological method, the nociceptive withdrawal reflex (NWR), and psychophysical measures, using hypothetical sample sizes for future studies as analytical goals. Thirty-four healthy volunteers participated in two identical experimental sessions, separated by 1 to 3 weeks. In each session, the cold pressor test (CPT) was used to induce CPM, and the NWR thresholds, electrical pain detection thresholds and pain intensity ratings after suprathreshold electrical stimulation were assessed before and during CPT. CPM was consistently detected by all methods, and the electrophysiological measures did not introduce additional variation to the assessment. In particular, 99% of the trials resulted in higher NWR thresholds during CPT, with an average increase of 3.4 mA (p<0.001). Similarly, 96% of the trials resulted in higher electrical pain detection thresholds during CPT, with an average increase of 2.2 mA (p<0.001). Pain intensity ratings after suprathreshold electrical stimulation were reduced during CPT in 84% of the trials, displaying an average decrease of 1.5 points in a numeric rating scale (p<0.001). Under these experimental conditions, CPM reliability was acceptable for all assessment methods in terms of sample sizes for potential experiments. The presented results are encouraging with regards to the use of the CPM as an assessment tool in experimental and clinical pain. Trial registration: Clinical Trials.gov NCT01636440.

Detecting dementia in patients with normal neuropsychological screening by Short Smell Test and Palmo-Mental Reflex Test: an observational study

BACKGROUND General practitioners (GPs) are in best position to suspect dementia. Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT) are widely used. Additional neurological tests may increase the accuracy of diagnosis. We aimed to evaluate diagnostic ability to detect dementia with a Short Smell Test (SST) and Palmo-Mental Reflex (PMR) in patients whose MMSE and CDT are normal, but who show signs of cognitive dysfunction. METHODS This was a 3.5-year cross-sectional observational study in the Memory Clinic of the University Department of Geriatrics in Bern, Switzerland. Participating patients with normal MMSE (>26 points) and CDT (>5 points) were referred by GPs because they suspected dementia. All were examined according to a standardized protocol. Diagnosis of dementia was based on DSM-IV TR criteria. We used SST and PMR to determine if they accurately detected dementia. RESULTS In our cohort, 154 patients suspected of dementia had normal MMSE and CDT test results. Of these, 17 (11 %) were demented. If SST or PMR were abnormal, sensitivity was 71 % (95 % CI 44-90 %), and specificity 64 % (95 % CI 55-72 %) for detecting dementia. If both tests were abnormal, sensitivity was 24 % (95 % CI 7-50 %), but specificity increased to 93 % (95 % CI 88-97 %). CONCLUSION Patients suspected of dementia, but with normal MMSE and CDT results, may benefit if SST and PMR are added as diagnostic tools. If both SST and PMR are abnormal, this is a red flag to investigate these patients further, even though their negative neuropsychological screening results.

Raum – Perspektive – Medium 2: Wahrnehmung im Blick. reflex: Tübinger Kunstgeschichte zum Bildwissen

Im zweiten Workshop zum Thema „Raum – Perspektive – Medium“, der im Februar 2009 am Kunsthistorischen Institut der Universität Tübingen stattfand, kristallisierten sich zwei zentrale Thesen heraus, die im nun folgenden Band aus interdisziplinärer Perspektive beleuchtet werden: Erstens die Frage nach dem Anteil des Betrachters am Bildprozess und zweitens eine damit einhergehende Bewertung des Medienbegriffs. In reflex 2 sind nun die Texte versammelt, die aus dem Workshop „Raum – Perspektive – Medium 2“ hervorgegangen sind.

Quantifying the vestibulo-ocular reflex with video-oculography: nature and frequency of artifacts

Video-oculography devices are now used to quantify the vestibulo-ocular reflex (VOR) at the bedside using the head impulse test (HIT). Little is known about the impact of disruptive phenomena (e.g. corrective saccades, nystagmus, fixation losses, eye-blink artifacts) on quantitative VOR assessment in acute vertigo. This study systematically characterized the frequency, nature, and impact of artifacts on HIT VOR measures. From a prospective study of 26 patients with acute vestibular syndrome (16 vestibular neuritis, 10 stroke), we classified findings using a structured coding manual. Of 1,358 individual HIT traces, 72% had abnormal disruptive saccades, 44% had at least one artifact, and 42% were uninterpretable. Physicians using quantitative recording devices to measure head impulse VOR responses for clinical diagnosis should be aware of the potential impact of disruptive eye movements and measurement artifacts.

The role of sensory neuron outgrowth in long-term sensitization of the tail-elicited tail-siphon withdrawal reflex of Aplysia

Neuronal outgrowth has been proposed in many systems as a mechanism underlying memory storage. For example, sensory neuron outgrowth is widely accepted as an underlying mechanism of long-term sensitization of defensive withdrawal reflexes in Aplysia. The hypothesis is that learning leads to outgrowth and consequently to the formation of new synapses, which in turn strengthen the neural circuit underlying the behavior. However, key experiments to test this hypothesis have never been performed. ^ Four days of sensitization training leads to outgrowth of siphon sensory neurons mediating the siphon-gill withdrawal response in Aplysia . We found that a similar training protocol produced robust outgrowth in tail sensory neurons mediating the tail siphon withdrawal reflex. In contrast, 1 day of training, which effectively induces long-term behavioral sensitization and synaptic facilitation, was not associated with neuronal outgrowth. Further examination of the effect of behavioral training protocols on sensory neuron outgrowth indicated that this structural modification is associated only with the most persistent forms of sensitization, and that the induction of these changes is dependent on the spacing of the training trials over multiple days. Therefore, we suggest that neuronal outgrowth is not a universal mechanism underlying long-term sensitization, but is involved only in the most persistent forms of the memory. ^ Sensory neuron outgrowth presumably contributes to long-term sensitization through formation of new synapses with follower motor neurons, but this hypothesis has never been directly tested. The contribution of outgrowth to long-term sensitization was assessed using confocal microscopy to examine sites of contact between physiologically connected pairs of sensory and motor neurons. Following 4 days of training, the strength of both the behavior and sensorimotor synapse and the number of appositions with follower neurons was enhanced only on the trained side of the animal. In contrast, outgrowth was induced on both sides of the animal, indicating that although sensory neuron outgrowth does appear to contribute to sensitization through the formation of new synapses, outgrowth alone is not sufficient to account for the effects of sensitization. This indicates that key regulatory steps are downstream from outgrowth, possibly in the targeting of new processes and activation of new synapses. ^

Carotid body chemoreceptor regulation of blood glucose during aerobic exercise

Regulación carótida en ejercicio aeróbico

The Aer protein and the serine chemoreceptor Tsr independently sense intracellular energy levels and transduce oxygen, redox, and energy signals for Escherichia coli behavior

We identified a protein, Aer, as a signal transducer that senses intracellular energy levels rather than the external environment and that transduces signals for aerotaxis (taxis to oxygen) and other energy-dependent behavioral responses in Escherichia coli. Domains in Aer are similar to the signaling domain in chemotaxis receptors and the putative oxygen-sensing domain of some transcriptional activators. A putative FAD-binding site in the N-terminal domain of Aer shares a consensus sequence with the NifL, Bat, and Wc-1 signal-transducing proteins that regulate gene expression in response to redox changes, oxygen, and blue light, respectively. A double mutant deficient in aer and tsr, which codes for the serine chemoreceptor, was negative for aerotaxis, redox taxis, and glycerol taxis, each of which requires the proton motive force and/or electron transport system for signaling. We propose that Aer and Tsr sense the proton motive force or cellular redox state and thereby integrate diverse signals that guide E. coli to environments where maximal energy is available for growth.