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B Linderoth

Publications and source records attributed to B Linderoth.

At least 55 records · Page 3Linked to original sources
PubMed1993

An animal model for the study of brain transmittor release in response to spinal cord stimulation in the awake, freely moving rat: preliminary results from the periaqueductal grey matter.

Electrical spinal cord stimulation (SCS) is an important method in the treatment of certain chronic pain syndromes which are difficult to manage with conventional techniques. The indications for this procedure have gradually narrowed to neuropathic pain states, especially those of peripheral origin, ischaemic pain due to peripheral vascular disease, and treatment-resistant angina pectoris. In spite of the clinical use of this method for more than 20 years, the mechanisms underlying the pain alleviating effect remain largely unknown. For the effect on ischaemic pain, recent animal research indicates a mediation via autonomic pathways. Concerning the effect on neuropathic pain progress in knowledge has been scanty. Data from spinal microdialysis in decerebrated or anaesthetized animals indicate the possible importance of serotonin and substance P in the dorsal horn for pain inhibition by SCS. However, data from experiments on anaesthetized animals are, for several reasons, not likely to truely reflect the mechanisms active in conscious humans under treatment with SCS. To avoid the influence of anaesthesia and to approach the clinical situation, we have developed an animal model enabling simultaneous SCS and supraspinal microdialysis in awake, freely moving rats. The animal model is described and some preliminary data indicating a release of gamma-amino butyric acid (GABA) induced by SCS in the periaqueductal grey matter (PAG), are presented.

Animals↗
PubMed1993

Release of neurotransmitters in the CNS by spinal cord stimulation: survey of present state of knowledge and recent experimental studies.

Electric stimulation applied to the posterior surface of the spinal cord (SCS) is an established treatment in certain chronic pain syndromes resistant to conventional therapeutic procedures. Despite the clinical value of SCS, the mechanisms behind the efficacy of the method are largely unknown. Several neurotransmitters in the CNS (e.g. opioids, serotonin, noradrenaline, substance P, GABA), have been proposed to be involved in the pain-alleviating effect of SCS. However, as yet there is no evidence that these would be involved in the beneficial effects of SCS. We have studied neurotransmitter release, using microdialysis techniques, in the spinal dorsal horn and the periaqueductal grey substance (PAG) of the rat and the cat, induced by SCS applied with current parameters equivalent to those used clinically in man. Up to now dialysates have been assayed for GABA, serotonin and substance P with highly sensitive methods. Three groups of studies have been carried out: (1) dorsal horn microdialysis in rats under halothane anesthesia during acute SCS; (2) dorsal horn microdialysis in cats under barbiturate anesthesia or following decerebration, and (3) PAG microdialysis in awake, unrestrained rats with chronic SCS. In the dorsal horn studies, microdialysis probes of different sizes were implanted in the lower lumbar dorsal horns. In the PAG studies, rats had guide cannulas for microdialysis stereotactically inserted into the PAG. SCS was applied at a low thoracic level with 50 or 100 Hz; 0.2 ms and an intensity amounting to 2/3 of the motor threshold. The microdialysis probes were perfused with modified Ringer's solution. Fractions of the dialysate were collected at various intervals. GABA and serotonin were assayed by reverse-phase HPLC, while substance P was investigated using a highly sensitive radioimmunoassay. SCS induced a significant release of GABA in the dorsal horn, most marked in the fraction following the stimulation period. In the rats with PAG microdialysis, the GABA level decreased significantly following two stimulation periods, although transitional increases during SCS were noted in some animals. In the decerebrated cat, a significant release of serotonin in the dorsal horn was obtained with SCS, while the levels of the metabolite 5-HIAA were little influenced by stimulation. On the contrary, in the decerebrated preparation there was no release of substance P in the dorsal horn with SCS, although in the intact cat under barbiturate anesthesia a significant release was induced.4+ off

Animals↗
PubMed1992

Dorsal column stimulation induces release of serotonin and substance P in the cat dorsal horn.

The neurohumoral mechanisms behind the pain-suppressing effect of dorsal column stimulation (DCS) still remain obscure. Experimental observations have indicated an inhibitory role for serotonin and, under certain conditions, also for substance P (SP), on nociceptive transmission in the spinal cord. Furthermore, some observations suggest that these substances might be involved in the effect of DCS. The present series of experiments was undertaken to investigate whether serotonin and SP are released in the dorsal horn by DCS. Twenty-one adult cats, in some experiments anesthetized, in others decerebrated at the midcollicular level, were used. Microdialysis probes were implanted bilaterally in lumbar dorsal horns (L5-L7) and perfused with Krebs' solution. Dialysates were analyzed for serotonin by high-performance liquid chromatography or for SP by radioimmunoassay. DCS was applied at the thoracolumbar junction with current parameters similar to those used clinically in humans. DCS induced a significant release of serotonin in the dorsal horn of decerebrated animals (173 +/- 83% increase; mean +/- standard error; n = 4; P less than 0.01), whereas the levels of the metabolite 5-hydroxyindoleacetic acid were not significantly influenced. In contrast, no release of SP could be recorded in response to DCS in the decerebrated preparation, although peripheral nociceptive stimulation (pinch) and noxious electric dorsal root stimulation induced an elevation of the SP levels. However, in intact animals DCS provoked a marked SP release in the dorsal horn (190 +/- 92% increase; n = 7; P less than 0.01). The release of serotonin and SP after DCS may indicate that these substances participate in the mediation of the pain alleviating effect of DCS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[Spinal cord stimulation in chronic neuropathic pain].

Seventeen years' experience of spinal cord stimulation in the treatment of chronic pain has shown it to be effective only in the case of neuropathic pain--in particular, pain due to lesions in peripheral nerves or posterior roots. In such cases, pharmacological treatment is often unsuccessful, and transcutaneous electrical nerve stimulation is only useful in certain cases. In a retrospective study of 84 patients followed for up to 16 years, 56 patients were still using their stimulators and reported continued pain relief. The majority suffered from peripheral neuralgia due to trauma or surgery and 72 per cent in that group enjoyed satisfactory relief. Trial stimulation via a temporary extension lead for at least 4-5 days is a prerequisite of good long-term results. It is concluded that spinal cord stimulation is an indispensable tool for treating chronic neuropathic pain, and it merits to be used more frequently.

Adult↗
PubMed1991

Bedside monitoring of regional cortical blood flow in comatose patients using laser Doppler flowmetry.

Continuous beside monitoring of regional cerebrocortical blood flow was carried out using laser Doppler flowmetry (LDF) in four comatose patients. Newly designed thin and flexible optical probes that were easily implanted into the cortex were employed. When the patients were in a deep comatose state, the recordings revealed a conspicuous relationship to intracranial pressure. As the patients improved, the flux values gradually increased, and the recordings showed characteristic changes in the wave pattern, presumably related to the restoration of an impaired cerebral autoregulation. Changes in regional cerebrocortical blood flow were also observed during routine nursing procedures, the use of medications, and voluntary activities, as demonstrated by one patient after a complete recovery. Although the volume of tissue scanned with LDF was limited, and the flux values did not directly express regional cerebrocortical blood flow in terms of milliliters per unit volume, changes in cerebral circulation were portrayed clearly in the flow recordings. Thus, LDF, which is simple to use, permits continuous bedside monitoring of the cerebral microcirculation. Its use should improve the management of comatose patients and also open avenues for a better understanding of the cerebral circulation in pathological states.

Adult↗
PubMed1991

Effects of sympathectomy on skin and muscle microcirculation during dorsal column stimulation: animal studies.

Electric stimulation of the dorsal spinal cord (DCS) in the treatment of pain in peripheral vascular disease is known to enhance peripheral circulation, but the mechanisms are still obscure. An earlier study has provided indirect evidence that the vasodilator effect is dependent upon alteration of sympathetic vasomotor activity. In the present study, surgical interruption of sympathetic pathways was performed to define the role of the sympathetic system for the stimulation-induced vasodilation. Three groups of normal rats were used: one group subjected to lumbar sympathectomy, one group sham-operated about 1 week before performing spinal cord stimulation, and a third group, without pretreatment, serving as a second control. Stimulation was applied to one dorsal column at the thoracolumbar junction, and peripheral microcirculation was recorded in hind limb skin and muscle by laser Doppler technique. The stimulation parameters were chosen to correspond with those used clinically in man. A cold test with monitoring of cold-induced changes in peripheral blood flow was used to assess the completeness of the sympathectomy. The preoperative cold test induced a reciprocal response, vasoconstriction in the skin and vasodilation in muscle. DCS with clinical parameters did not produce this reciprocity in the control and sham-operated rats, but induced a vasodilation in both skin and muscle. After complete sympathectomy, defined as postoperative disappearance of the vasomotor responses to cold, the vasodilation in skin and muscle in response to DCS was abolished; however, the vasodilatory response to high-intensity stimulation (approximately 10 times the motor threshold) was not affected. Incomplete sympathetic denervation in some animals resulted in partial preservation of a vasodilatory response to DCS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Peripheral vasodilatation after spinal cord stimulation: animal studies of putative effector mechanisms.

Spinal cord stimulation has been reported to relieve ischemic pain and to enhance peripheral circulation. To elucidate the still unknown mechanisms behind these effects, changes in the peripheral blood flow in the skin of the hind paw after stimulation applied to the dorsal column was studied in the normal rat. A substantial flow increase, monitored by laser Doppler technique, was observed in response to stimulation with an intensity comparable to that used clinically in man, recruiting only low-threshold neuronal elements. The response remained after transection of the dorsal roots, as well as after spinal cord section rostrally to the stimulating electrode. Furthermore, monitoring of antidromic compound action potentials in a peripheral nerve indicated that the stimulus intensity applied to dorsal columns recruited solely low-threshold, large-diameter fibers. Stimulation failed to produce an increase in blood flow in addition to that produced by guanethidine and hexamethonium, but high-intensity dorsal column or dorsal root stimulation still was effective. The results indicate that spinal mechanisms are essential and that antidromic activation of primary afferent fibers is unlikely to account for the peripheral vasodilatation induced by low-intensity spinal cord stimulation. Our observations suggest a transitory inhibition of sympathetic vasoconstriction as the principal underlying mechanism.

Action Potentials↗
PubMed1990

In vivo release of serotonin in cat dorsal vagal complex and cervical ventral horn induced by electrical stimulation of the medullary raphe nuclei.

Extracellular levels of serotonin (5-hydroxytryptamine; 5-HT) were monitored by microdialysis in the dorsal vagal complex (DVC) and the ventral horn of the spinal cord at the level of the phrenic motor nucleus in decerebrated cats. A selective serotonin uptake inhibitor, alaproclate (10(-4) M) was included in the dialysis probe perfusion fluid to increase basal and stimulated levels of 5-HT. Electrical stimulation (30 Hz, 10 V, 0.5 ms) in the nucleus raphe obscurus, containing neurons projecting to the DVC and to the ventral horn, induced a 2-3-fold increase of the 5-HT release in both these regions. After termination of the stimulation, the release gradually decreased during the following 60 min. Substance P, which coexists with 5-HT in descending neurons, did not significantly affect the 5-HT release when it was added (100 microM) to the probe perfusion fluid. The present findings are in accordance with the hypothesis that prolonged release of 5-HT is responsible for the previously demonstrated long-lasting facilitation of phrenic activity following raphe obscurus stimulation.

Animals↗
PubMed1990

Microdialysis in the human brain: extracellular measurements in the thalamus of parkinsonian patients.

Microdialysis in the human brain has been performed for the first time during thalamotomy intended to relieve tremor in patients with Parkinson's disease. The aim was to test the reliability of the microdialysis technique for biochemical characterization of a target area in the human brain during a routine operation. Microdialysis probes were introduced through the same trajectory as the lesioning electrode thus causing no additional damage to the brain. Dopamine, DOPAC, HVA, 5-HIAA, hypoxanthine, inosine, guanosine, adenosine, GABA, taurine, aspartate and glutamate were measured in the perfusate from the target region - the Vim nucleus. The results show initial high levels that reach baseline levels after 10-20 minutes. Surprisingly, consistent and reproducible levels were found, the only exception being one patient on 1-DOPA therapy who had elevated DA and metabolite levels.

Aged↗
PubMed1989

Is vasodilatation following dorsal column stimulation mediated by antidromic activation of small diameter afferents?

It is well-known that high intensity electrical stimulation of peripheral nerves and dorsal root fibres causes vasodilatation. However, the mechanisms underlying the vasodilatory effect of stimulation applied to the dorsal columns (DCS), with an intensity insufficient to recruit small diameter, high threshold fibres are virtually unknown. The present project was planned to elucidate underlying neural mechanisms. Albino rats, anaesthetized, paralyzed and artificially ventilated were used. Electrical stimulation with different parameters was applied to various sites of the exposed spinal cord, root fibres and peripheral nerves. In some experiments the spinal cord, root fibres or peripheral nerves were transected. Peripheral blood flow was recorded using laser Doppler technique. With stimulation of the lower thoracic region at low intensity substantially increased blood flow in the ipsilateral hind paw. The compound action potentials from the gural nerve displayed only components from low threshold, rapidly conducting fibres without detectable late components. Transection of the spinal cord above the stimulation site did not affect the blood flow changes. Also low intensity stimulation of the proximal part of a sectioned dorsal root resulted in a substantial rise in peripheral blood flow, whereas the same intensity proved ineffective when applied to the distal stump. High intensity stimulation of the distal stump not unexpectedly, caused a major increase in blood flow. The findings in the present study implicate the importance of a central circuit for the effect, whereas antidromic activation of primary afferents seems to be a less likely explanation. Possibly, stimulation induces a transitory inhibition of sympathetic vasoconstrictor tone, though activation of sympathetic vasodilatory efferents cannot be excluded.

Afferent Pathways↗
PubMed1989

Paroxysmal facial pain in disseminated sclerosis treated by retrogasserian glycerol injection.

In the material of patients with trigeminal neuralgia treated by retrogasserian glycerol injection at the Karolinska Hospital, 23 cases (8%) were also diagnosed as suffering from disseminated sclerosis. These patients were often on carbamazepine treatment before the procedure, a regimen known to cause severe side effects and increase pre-existing symptoms in patients with multiple sclerosis. Following glycerol injection, more than 90% became pain-free within the first 2 months and 82% could discontinue drug therapy. This initial outcome corresponds well to the results in our larger series, but the long-term results in the group with multiple sclerosis is less satisfactory, with 61% recurrence at follow-up 8-79 months following treatment. In total 48% were pain-free at follow-up, following reinjections in 8 cases. In spite of less satisfactory long-term results, more than three-fourths of the patients wanted another glycerol injection after only low-dose trial with carbamazepine in case of recurrence.

Adult↗
PubMed1989

Intrathecal baclofen for long-term treatment of spasticity: a multi-centre study.

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.

Adult↗
PubMed1988

Easy peroperative classification of perianal muscle as external or internal sphincter by means of diathermy.

Cutting tissues with coagulation current diathermy has some advantages in anorectal surgery. By evoking twitches in striated muscle and no similar reaction in smooth muscle, the technique facilitates the distinction between internal and external anal sphincter. Furthermore, cutting in this manner avoids the use of sharp instruments, thereby lowering the risk of accidental perioperative spread of blood-borne viral disease.

Anal Canal↗
PubMed1988

Tachykinin release from rat spinal cord in vitro and in vivo in response to various stimuli.

The aim of the present study was to establish an experimental model, previously used in cat, for studying tachykinin release from the rat spinal cord in vivo and to compare the results with those obtained in vitro. Stimulation with pulses of 40 mM potassium or 10 microM capsaicin in the spinal cord superfusion fluid increased the release of substance P (SP)- and neurokinin A (NKA)-like immunoreactivity (LI) both in vivo and in vitro. The amounts of SP-LI and NKA-LI released by potassium in vitro were 1.02 +/- 0.12 and 1.17 +/- 0.22 fmol/mg tissue, respectively. Also the ratio between the amounts released by two consecutive potassium stimulations were similar for SP-LI and NKA-LI. Reversed-phase high performance liquid chromatography of the NKA-LI released in vitro by potassium or capsaicin revealed a major immunoreactive component coeluting with synthetic NKA. Despite the use of highly sensitive radioimmunoassays, basal release of SP-LI and NKA-LI was found only in 9 of 31 in vivo experiments. In these, peripheral electrical stimulation of the sciatic nerves (50 Hz, 50 V and 0.05 ms or 10 Hz, 10 V and 5 ms) induced an increase of the SP-LI and NKA-LI levels in the superfusates. This increase persisted for more than 40 min after a 2 min stimulation. In most experiments, however, no SP-LI or NKA-LI could be detected in the superfusates, neither at basal conditions nor following electrical nerve stimulation. Similarly, no release of SP-LI could be detected in response to various noxious mechanical, thermal or chemical stimuli applied to the skin. The present results demonstrate that the superfused rat spinal cord may be used to study in vivo release of tachykinins in response to intense chemical stimulation of the entire spinal cord. However, the method seems to be less suitable for studies of tachykinin release in response to electrical activation engaging only a few spinal segments or in response to natural noxious stimuli. The results obtained in vitro suggest that SP and NKA are released in equimolar amounts from the spinal cord upon stimulation with potassium.

Animals↗
PubMed1987

In vivo release of substance P in cat dorsal horn studied with microdialysis.

Variations in the extracellular concentration of substance P (SP) were measured in cat dorsal horn in vivo by microdialysis and radioimmunoassay. Electrical unilateral stimulation of the sciatic nerve was used to evoke release of SP. At high-intensity stimulation, activating slowly conducting (approx. 0.9 m/s) fibres, there was an increase in substance P-like immunoreactivity (SP-LI) to 338% of the preceding control value (P less than 0.05, n = 5) in the dialysates collected at levels L6-L7 at the stimulated side. A less pronounced increase, to 164% of the basal level, was found at the contralateral side. More cranially (L1-L5) in the dorsal horn at the stimulated side, only a moderate or no increase in SP-LI was seen. Stimulation with low intensity, sufficient to activate fast (greater than 20 m/s), but not slowly conducting fibres, evoked no increase in SP-LI. The results indicate that unilateral peripheral C-fibre activation induces a local SP release in the dorsal horn present also on the side not stimulated.

Action Potentials↗
PubMed1985

Possible neurohumoral mechanisms in CNS stimulation for pain suppression.

Improved knowledge about biochemical mechanisms underlying pain suppression by CNS electric stimulation is one condition for the further advancement of this form of treatment. In 6 patients treated with PVG stimulation and in 14 with spinal cord stimulation the concentration of substance P-like immunoreactivity in lumbar CSF increased significantly following stimulation. However, these changes may be unspecific and not directly related to the suppression of pain. Measurements of somatostatin, cholecystokinin, vasoactive intestinal polypeptide, neurotensin and monoamine metabolites in CSF showed no changes related to stimulation and the ensuing pain relief. Possible reasons for these negative findings are discussed.

Brain↗