Responsiveness of chronic pain to morphine.
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Biomedical subjects
Publications and source records attributed to J Gybels.
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A 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 micron +/- 0.15 compared with 0.71 micron +/- 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.
A patient is reported who was treated successfully for a left thalamic abscess that resulted in subcortical aphasia. A SPECT scan showed large areas of hypoperfusion in the cortex of the left hemisphere. At follow up after seven months there was marked improvement in the language disorder and the cortical hypoperfusion. It is suggested that aphasia in patients with subcortical lesions results from secondary cortical dysfunctions. The evidence is confined to patients with stroke lesions. The possible implications of this case on current theories of pathophysiological mechanisms, in particular the ischaemic penumbra theory and the cortical diaschisis theory, are briefly discussed. Cortical diaschisis may be the appropriate explanation in this patient.
In current clinical practice, two brain structures are stimulated for the relief of chronic pain, namely the somatosensory thalamic nuclei (VPL-VPM) and the periventricular and periaqueductal gray matter (PVG-PAG). Whereas stimulation of the VPL-VPM is almost exclusively used for the treatment of deafferentation pain, stimulation of the PVG-PAG is mostly used in cases of nociceptive pain. We present our results of VPL-VPM stimulation in 36 patients with deafferentation pain. Initial pain relief was obtained in 61% of patients. To-day, after a mean follow-up of more than 4 years, 30% are still pain free. This success rate was found to be lower than the mean reported success rate of 57%, based on a survey of the world literature. Upon reviewing the literature, it was apparent that the reported success rates vary considerably between different authors. Some tentative explanations are given for this large discrepancy in success rate. The mechanisms by which electrical stimulation of the VPL-VPM suppresses deafferentation pain remain to be elucidated. Recent clinical and experimental findings suggest that a dopaminergic mechanism might be involved.
We have developed a prototype display workstation for use in stereotactic neurosurgery. Patient image data from computed tomography, magnetic resonance imaging, and digital subtraction angiography are acquired with the stereotactic frame in place and subsequently transferred to the workstation for further processing. Target points may be identified on any image type and probe trajectories defined. Any point or line indicated on one set of images may be transferred immediately to other images, to determine, for instance, safe avascular probe paths. We present some general outlines for the use of computers for stereotactic neurosurgery and discuss the different components of the current system. Finally, we make some suggestions as to further developments.
Pentobarbital-anesthetized rats received electrical hindpaw stimulation every 10 s to elicit a maximal hindlimb withdrawal reflex. The integrated EMG response in the ipsilateral tibialis anterior was sampled by a computer which also controlled the timing of electrical stimuli applied to the brain. A suppression of the evoked flexor activity was obtained with currents below 0.05 mA for stimuli applied in the medial hypothalamic region. A second effective site was located in the paraventricular area of the thalamus. The suppression had an onset latency of 30 ms, increased over a period of 500 ms and was followed by a postinhibitory facilitation (rebound). When the noxious electrical shocks were given over prolonged periods (140 s) the suppression of the flexor reflex was seen to outlast the central stimulation by more than 100 s. Intravenous injection of naloxone or methysergide failed to reverse the effects of the brain stimuli. It is suggested that the hypothalamic induced inhibition of withdrawal reflexes is functionally meaningful in view of the incompatibility between these reflexes and the locomotor behavior which is part of the behavioral responses (i.e. fight or flight) controlled by this area.
The literature on myelotomy for the treatment of chronic pain was reviewed and a total of 635 published cases scrutinized. Two main modes of myelotomy can be distinguished 1) a longitudinal commissural section tuned to the segmental pain level and 2) a focused central lesion, irrespective of considerations of the metameric pain distribution, mainly carried out at a high cervical level. Of the longitudinal commissural myelotomy, a posteriorly restricted and a complete type can moreover be discerned. The pain relief decays with time after myelotomy of any kind. Central myelotomy scores better than complete commissural section for malignant pain in a statistically significant manner but its superiority over posterior commissurotomy cannot be statistically proven. Except of a girdle-shaped hypo-algesia, which is expected after the section of the decussating spinothalamic fibers in a complete commissurotomy, other--irregular--patterns of hypo-algesia have been observed, especially after central myelotomy. This unusual lesion, provoking unusual hypo-algesia patterns, together with phenomena like a preserved sharp-blunt-discrimination within the hypo-algesic area, points at a different sensory channel that might be severed in a central myelotomy as compared with an anterolateral chordotomy or a complete commissurotomy. This hypothesis is matched with recent physiological evidences.
Twenty eight patients with severe, intractable spasticity have been treated by chronic intrathecal administration of baclofen. An implantable programmable drug-administration-device (DAD) was used with a permanent intrathecal catheter. Infusion of 50 to 800 micrograms/day of baclofen completely abolished spasticity. Follow-up was up to two years. Therapeutic effect was documented by clinical assessment of tone, spasms and reflexes and by electrophysiological recordings of mono- and polysynaptic reflex activity. Complications and untoward side-effects of the procedure were few. This procedure is recommended for spasticity of spinal origin refractory to physiotherapy and oral medication. It is a preferable alternative to ablative surgical intervention.
A new method for the study of stimulation-produced analgesia is introduced. The hindlimb flexor EMG, in response to noxious electrical stimulation of the paw, is used as an indirect index of analgesia induced by electrical stimulation at different brain sites. In the lightly anesthetized rat (pentobarbital 10-20 mg/kg/h) such responses are quite stable and easily evoked at intertrial intervals as short as 10 s without habituation. The high repetition rate allows a rapid determination of the threshold current intensities or the brain stimuli required to suppress the hindlimb withdrawal. The test is objective, avoids skin damage and sensitization and can be performed semi-automatically when implemented with a small PC.
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An accessory locating device to the existing BRW stereotactic system is presented. It can be used as a reference device to locate angiographic data with respect to the BRW stereotactic system. Hence, the projection of target points onto angiograms, visible on CT scans, are easily calculated, as well as the stereotactic coordinates of a set of points (e.g., AVM) indicated on at least two angiograms. As a final result integrated images of cerebral blood vessels and an outline of tumor lesions can be generated using more sophisticated computer equipment.
Preliminary experience with a newly constructed angiographic localizer system for use in stereotactic neurosurgery is reported. This localizer ring, mounted on the BRW head ring, allows for the transformation of target points with known stereotactic coordinates (e.g., visible on computerized tomography scans) onto angiograms, as well as the determination of stereotactic coordinates of a set of points (e.g., arteriovenous malformations) indicated on at least two angiograms.
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.
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.
Knowledge about the pathogenesis of certain human diseases and how to treat them, has in general been advanced by the availability of a reasonably similar disease counterpart somewhere else in the animal kingdom. Unfortunately, a model of chronic pain is difficult to come by because of the inherent problem of defining animal pain, and it is only in recent years that such models have been proposed, and a study of them has started. The purpose of the present short review has been therefore to summarize some of the major developments in this field in such a way as to assist the reader in deciding just how exciting prospects in chronic pain research for the future might be.
The event-related potential (ERP), produced by subjects who were experiencing a gradually increasing heat stimulus, was recorded 3.5 sec before and 1 sec after a motor response. Subjects responded when the stimulus was 'just warm,' 'just at prickling pain' or 'above the temperature of just prickling pain.' Two control procedures mimicked the readiness potential (RP) and motor potential (MP) experiments. The results showed that the steadily rising negative MP was modified to a positive wave before the decision of 'warm.' During the 'pain' and 'above pain' conditions, the pre-decision slow wave was less negative than the MP but less positive than that of the 'warm' condition. A temperature control condition confirmed that rising temperature alone did not produce these results. Principal components analysis confirmed these differences by producing factors which were interpreted as representing the ERPs of the conditions of 'warm,' 'pain,' 'above pain,' RP and MP. It was evident from pilot studies that uncontrolled electrical activity from the skin potential response (SPR) was contaminating the results. SPR forced all ERP curves in the positive direction and several attempts to eliminate the SPR from the ERP data failed. While the SPR was produced differentially across conditions and across the experimental session, the smaller the variability in the electro-oculogram (EOG) recorded from above and below the orbits, the smaller was the SPR contamination that we recorded in the ERP. Therefore, we selected subjects for this experiment who showed a stable orbital EOG.
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