J. Van Hees

Further evidence for myelinated as well as unmyelinated fibre damage in a rat model of neuropathic pain

SummaryA mononeuropathy, produced by ligation of the sciatic nerve in rats, has recently been proposed as an animal model of experimental pain and pain-related disorders (hyperalgesia and allodynia). We investigated quantitatively the morphological changes in myelinated and unmyelinated fibres of the sciatic nerves 2 weeks after ligation in rats exhibiting allodynia to thermal stimulation. There was a marked reduction in the number of large myelinated fibres distal to the ligature (711 ± 34 compared with 5315 ± 230 in normal nerves). We also found a significant loss of small myelinated fibres (2429 ± 109 compared with 3197 ± 308 in normal nerves), the remaining fibres of this type showing pathological properties. Finally, ultrastructural evidence of damage to unmyelinated fibres was found. The typical pattern of large clusters of normal unmyelinated axons was no longer present within most regions of the nerve. There was a significant reduction in the size of the unmyelinated fibres (0.41 μm ± 0.15 compared with 0.71 μm ± 0.08 in normal nerves), together with a twofold increase in their number per cluster. Hypotheses about the mechanism of thermal allodynia in this pain model therefore must take into account the fact that all fibre classes show pathological changes.

Suppression of C-fibre discharges upon repeated heat stimulation may explain characteristics of concomitant pain sensations

Nociceptors with unmyelinated axons were recorded from the superficial radial nerves of 7 volunteers. A sequence of uniform radiant heat stimuli of 18 s duration, starting from an individually adjusted adapting temperature were used to raise the skin surface temperature by 6 degrees C to a painful level (41-43 degrees C). These stimuli followed each other at 3 different interstimulus intervals of 35 s, 70 s and 105 s, occurring in a random order. The subjects were asked to track the time course of the stimulus-evoked sensation by manipulating the length of a light bar. Adaptation and stimulus temperatures were chosen to induce sensations of heat and/or pain. All nociceptors studied responded to these stimuli with a phasic response of 3-5 s duration, often followed by a low frequency tonic discharge, lasting as long as the stimulus. No discharges were seen in interstimulus periods. Discharge rates during the phasic responses were linearly related to interval duration, whereas tonic discharges were not influenced by the preceding interval. In parallel readings of pain responses were lower up to the 10th second of the stimulus after short rather than after long intervals. These results indicate that the suppression of C-fibre nociceptor discharges during repetitive stimulation may explain concomitant reductions in the magnitude of human pain sensations.

Histochemical changes of substance P, FRAP, serotonin and succinic dehydrogenase in the spinal cord of rats with adjuvant arthritis

Various histochemical changes were found in spinal segments L4-L5 of rats with adjuvant arthritis, predominantly 30 days after inoculation. A slight to marked increase of substance P immunoreactivity occurred in laminae I, II and X. FRAP activity was enhanced in lamina II. Serotonin immunoreactivity was heavier in laminae I, VIII and IX in a few animals. The intensity of the histoenzymological reaction for succinic dehydrogenase increased in certain laminae VIII and X neurons. At day 15 of the disease the increase of substance P and FRAP activities was chiefly restricted to the medial portion of the superficial dorsal horn. There was a significant positive correlation between the scratching behaviour of arthritic rats and the substance P immunoreactivity in laminae X and I. If one accepts that scratching is pain-related, the data are consistent with a possible role of substance P in the chronic pain associated with adjuvant arthritis. They leave undetermined the significance of the other histochemical changes.

Magnesium deficiency as a cause of acute intractable seizures

SummaryClinical and experimental investigations have shown that magnesium depletion causes a marked irritability of the nervous system, eventually resulting in epileptic seizures. Although magnesium deficiency as a cause of epilepsy is uncommon, its recognition and correction may prove life-saving. Two case reports are presented which emphasize the importance of recognizing hypomagnesaemia in patients with acute intractable seizures.

A new muscle artifact removal technique to improve the interpretation of the ictal scalp electroencephalogram

In this paper a new method for muscle artifact removal in EEG is presented, based on canonical correlation analysis (CCA) as a blind source separation technique (BSS). This method is demonstrated on a synthetic data set. The method outperformed a low pass filter with different cutoff frequencies and an independent component analysis (ICA) based technique for muscle artifact removal. The first preliminary results of a clinical study on 26 ictal EEGs of patients with refractory epilepsy illustrated that the removal of muscle artifact results in a better interpretation of the ictal EEG, leading to an earlier detection of the seizure onset and a better localization of the seizures onset zone. These findings make the current method indispensable for every epilepsy monitoring unit

Sensations and trigeminal somatosensory-evoked potentials elicited by electrical stimulation of endosseous oral implants in humans

The perception of bipolar electrical stimuli through implants was studied. The stimuli were delivered to permucosal oral endosseous implants in 15 individuals, who then reported tapping to beating sensations. In 10 out of the 15, these stimuli evoked clearly distinguishable potentials in the averaged electroencephalograms. The most prominent scalp potential was a positive wave with a latency between 18 and 25 ms, often preceded by a negative wave with a latency around 12-17 ms. In contrast, when a motor response was elicited by stimulation of the lip, a shorter latency wave around 8-11 ms was found additionally, indicating that the former-mentioned waves represent a true sensory response and not an artefact of myogenous origin. Furthermore, topical anaesthesia of the gingiva surrounding the implants in six individuals had little effect on the sensory responses. This evidence excluded peri-implant mucosal innervation as the origin of the perception and of the somatosensory-evoked waves elicited by the electrical stimulation of the oral implants. To the best of our knowledge, for the first time a sensation (osseoperception) has been elicited by electrical stimulation of endosseous oral implants and correlated with simultaneously recorded trigeminal somatosensory-evoked potentials (TSEPs).

SINGLE AFFERENT C FIBER ACTIVITY IN THE HUMAN NERVE DURING PAINFUL AND NON PAINFUL SKIN STIMULATION WITH RADIANT HEAT

Publisher Summary This chapter discusses single afferent C fiber activity in the human nerve during painful and non-painful skin stimulation with radiant heat. The chapter presents a study to analyze single fiber activity in five polymodal nociceptive C fibers in relation to skin temperature, using radiant heat stimulation, in awake human subjects. The recordings were made with tungsten microelectrodes in the superficial branch of the radial nerve. The chapter presents the results of 173 stimulations in 5 different C units. The fiber activity is expressed as the mean firing frequency during the stimulus application (about 15 seconds if tolerated). Different skin temperatures between 40°C and 55°C are administered in repeated series. Between each stimulus, the skin is allowed to cool down to 35°C. The afferent activity is of rather low frequency and does not, as a rule, exceed 2 spikes/s even for stimuli reported as strongly painful. Clear pain sensations do not require a massive C-fiber discharge. C-fiber activity of very low frequency (below 0.3 spikes/s) does not necessarily elicit pain sensation.

A hypothetical immunemediated unifying mechanism for the holmes-Adie syndrome

The Holmes-Adie syndrome consists of pupillotonia, arreflexia and autonomic dysfunction. Some explanations for these different symptoms have been attempted, centred upon neuropathological and electrophysiological findings. A hypothetical immunemediated mechanism, as in the Guillain Barré syndrome, is presented in this paper for explaining the three chief symptoms of the syndrome.

Noxious Cutaneous Input and the Tactile Exploratory Function of the Skin of the Hand

In daily life, during skillful motor behaviour such as violin playing, or during tactile exploratory behaviour, the skin of the hand is subjected to possible noxious agents without the subject’s experiencing a pain sensation. In other words, under certain conditions, the skin’s nociception function is subordinated to the explorative role of the skin.