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Biomedical subjects

M Zimmermann

Publications and source records attributed to M Zimmermann.

At least 361 records · Page 20Linked to original sources

[Pain and pain therapy - neurophysiologic view].

Usually, pain is caused by the excitation of nociceptors or of nociceptive afferent fibers. The responsiveness of the nociceptors can be modulated by endogenously released algesic substances or local hormones. Lesioned and regenerating nerve fibers show enhanced excitability and spontaneous activity. Motor and sympathetic reflexes sometimes have an excitatory action on nociceptors, a positive feedback which often is essential in chronic pain states such as the sympathetic reflex dystrophies. Proper diagnosis of these influences on nociceptor excitation is crucial if therapeutic interference is to be rendered possible at the peripheral site of encoding of pain stimuli. No pain center exists in the central nervous system. The cognitive, affective, motor and vegetative dimensions of pain perception and pain behaviour are based on a complex interaction of several brain systems. An important feature of brain function in relation to pain is the fact that nervous information related to pain can be modulated in the central nervous system. Various inhibitory modulations have recently been described which may be used for pain therapy. Inhibition of spinal neurons, and analgesia, can be produced by stimulation of brain stem structures. Pharmacologically, pain inhibitory systems may involve serotonin and endogenous opioids as transmitter or modulator substances. For pain therapy, pain inhibitory systems may be activated e.g. by morphine and ther analgesic drugs, focal brain stimulation, various means of somatosensory afferent stimulation and by psychological influences such as stress.

Afferent Pathways↗

Effect of iontophoretically applied 5-hydroxytryptamine on the excitability of single primary afferent C- and A-fibers in the cat spinal cord.

Excitability testing of single sural afferent C- and A-fibers was employed to study possible presynaptic effects of 5-hydroxytryptamine (5-HT) applied iontophoretically at the intraspinal point of lowest threshold for their antidromic activation in anesthetized or decerebrate spinalized cats. Threshold for single fibers recorded in the sural nerve was measured prior to and during iontophoretic application of 5-HT through a micropipette positioned in close proximity to the intraspinal stimulating electrode. 5-HT produced dose-related increases in threshold for antidromic activation in 21 or 30 C-fibers. Six of 9 A delta, and 4 of 7 A beta-fibers were similarly affected.

Afferent Pathways↗

Serotonergic mediation of descending inhibition from midbrain periaqueductal gray, but not reticular formation, or spinal nociceptive transmission in the cat.

Electrical stimulation in the midbrain periaqueductal gray (PAG) and lateral midbrain reticular formation (LRF) strongly suppresses the responses of spinal dorsal horn neurons to noxious heating of the skin. The possible role of serotonin (5-hydroxytryptamine, 5-HT) was investigated by quantitatively comparing certain parameters of descending inhibition from PAG and LRF in normal cats [14,15] and cats whose central 5-HT levels had been reduced by pretreatment with p-chlorophenylalanine (PCPA, 300 or 500 mg/kg i.p., 72 h prior to acute experiment). Single lumbar dorsal horn neuronal responses to noxious radiant heating of glabrous footpad skin(50 degrees C, 10 sec, 1/3 min) were recorded in normal and PCPA-pretreated cats anesthetized with sodium pentobarbital and N2O. Inhibition of neuronal heat-evoked responses during midbrain stimulation (mean frequency 30 Hz, up to 800 microA current intensity) was expressed as percent of the unit's control response in the absence of midbrain stimulation. Inhibition by PAG stimulation of units from cats pretreated with 300 mg/kg PCPA (mean inhibition at 450 microA to 60% of control in 12 units) was not detectably different from that in control (non-pretreated) cats. However, inhibition by PAG stimulation was significantly weaker in units from cats pretreated with 500 mg/kg PCPA (mean to 83.4% of control in 9 units). In the latter group, mean current threshold for inhibition was higher, and slope of current-intensity plots lower, than in the control and 300 mg/kg PCPA pretreatment groups. In contrast, mean inhibition by LRF stimulation was enhanced in the 300 and 500 mg/kg PCPA treatment groups in a dose-related manner. In normal (non-pretreated) cats, systemic administration of the putative 5-HT antagonist methysergide (0.07--1 mg/kg) reduced or abolished inhibition by PAG stimulation in each of 8 units. Low doses of methysergide had little or no effect on inhibition produced by LRF stimulation in 6 units. The results suggest pharmacologically distinct mechanisms of inhibition produced by stimulation in PAG and LRF.

Animals↗

Time course and effective sites for inhibition from midbrain periaqueductal gray of spinal dorsal horn neuronal responses to cutaneous stimuli in the cat.

Inhibition of spinal dorsal horn neuronal responses to noxious (50 degrees C) skin heating by stimulation of the midbrain periaqueductal gray (PAG) was quantitatively investigated in cats anesthetized with sodium pentobarbital and nitrous oxide. Systematic variation of the interval between onset of PAG stimulation (PAGS) and onset of noxious skin heating revealed that a marked reduction of spinal unit heat-evoked discharges occured immediately upon onset of PAGS, and ceased immediately at offset of PAGS with a post-stimulation excitatory rebound. Stimulation at sites in both ventral and dorsal PAG produced inhibition, the strength of which increased sometimes in a linear manner with increasing strength of PAGS. Thresholds for the generation of descending inhibition were higher in dorsal than ventral PAG. PAGS also inhibited spinal unit responses to non-noxious skin stimulation (brushing of hairs). Descending inhibition from PAG is considered as a possible mechanism for analgesia produced by stimulation of PAG and other brainstem structures.

Animals↗

Calendar life span versus budding life span of Saccharomyces cerevisiae.

This investigation is concerned with the internal factors governing the life span of individual yeast cells. The life span may be limited either by the number of buds a cell can produce or by internal measurement of metabolic time. The natural relationship between the number of cells a single cell can produce and the passage of time was modified by three different kinds of treatment: (1) by cooling the cells for several hours each day; (2) by preculturing the cells in media which inhibit cell division before allowing logarithmic growth; and (3) by culturing the cells in a medium which reduces the rate of budding. All these methods led to a prolongation of chronological life span, but the life span measured by the number of buddings remained remarkably constant. We therefore conclude that there is some kind of factor involved in the budding process which determines life span.

Cell Division↗

The opiate antagonist naloxone does not consistently block inhibition of spinal nociceptive transmission produced by stimulation in lateral midbrain reticular formation of the cat.

Electrical stimulation in the lateral midbrain reticular formation (LRF) inhibited the responses of spinal dorsal horn neurons to noxious (50 degrees C) skin heating. Systemic administration of naloxone (0.1-2 mg/kg) had no effect on inhibition produced by LRF stimulation in 10 units, while this inhibition was partially blocked in 3 units. The results indicate that endogenous opiates are not primarily involved in mediating descending inhibition from LRF stimulation.

Afferent Pathways↗

Irreverisble differential block of A- and C-fibres following local nerve heating in the cat.

1. Local heating of a nerve was used to block conduction in the myelinated or A-fibres while preserving normal function in most of the non-myelinated or C-fibres. Compound action potentials of A- and C-fibres, and impulses in single C-fibres were recorded to measure the block. 2. Most experiments were done on the posterior tibial nerve of the cat's hind limb. Conducted heat was applied in successive periods of about 2 min each to 15 mm of the exposed nerve. 3. The range of temperatures used was between 45 and 52 degrees C. Below 46 degrees C no conduction block was obtained. With increasing temperature the cumulative time of heating required to produce a block in at least 99% of A-fibres decreased from around 110 min at 46.5 degrees C to 10 min at 51 degrees C. 4. In the posterior tibial nerve the C-fibre compound action potential was reduced to 0.66 of control (mean of twenty-two experiments) when the A-fibre action potential was less than 1% of control. The corresponding value of this selectivity coefficient was 0.20 in seven superficial peroneal and sural nerves. 5. Once a conduction block of A-fibres was reached the remaining C-fibres showed normal functioning, including conduction of repetitive impulses at up to 30 Hz evoked by electrical nerve and adequate skin stimulation. C-fibre conduction persisted for at least 33 h, but not longer than 3 days. 6. This pure C-fibre nerve might be useful for studying central nervous system effects of C-fibres.

Action Potentials↗

Differential inhibitory effects of medial and lateral midbrain stimulation on spinal neuronal discharges to noxious skin heating in the cat.

1. The inhibitory effects of electrical stimulation in midbrain periaqueductal gray (PAG) and lateral reticular formation (LRF) on spinal dorsal horn neuronal responses to noxious skin heating were investigated in cats anesthetized with Nembutal and N2O. 2. Thirty-one dorsal horn units driven by electrical stimulation of the posterior tibial and/or superficial peroneal nerves at A- and C-fiber strength responded to noxious radiant heating (e.g., 50 degrees C) of the skin of the hindpaw. All units tested were inhibited by electrical stimulation (100-Hz trains, 3/s) of both PAG and LRF. 3. Systematic tracking with the stimulating electrode revealed that descending inhibition is generated at sites throughout the mediolateral extent of the midbrain. Particularly effective sites were in LRF and PAG. 4. More powerful descending inhibition was generated from LRF than from PAG sites, based on quantitative comparison in the same unit of a) degree of inhibition of spinal unit heat-evoked discharges by PAG and LRF stimulation at the same current intensity, b) current threshold for inhibition by PAG and LRF stimulation, and c) slope of curves plotting degree of inhibition in relation to intensity of PAG and LRF stimulation. 5. Dorsal horn neurons show a linear relationship between response magnitude and temperature of skin heating during a series of heat stimuli (42-50 degrees C) applied at 3-min intervals. When the series is repeated during PAG stimulation, the slope of the linear temperature-response curve is reduced without a change in the response threshold. In contrast, repetition of the heating series during LRF stimulation produced a parallel rightward shift in the linear temperature-response curve, with commensurate increase in response threshold. 6. The results indicate that functionally separate descending inhibitory systems are activated by stimulation of PAG and LRF. Possible inhibitory mechanisms and the functional significance of descending inhibition from PAG and LRF are discussed.

Animals↗

The opiate antagonist, naloxone, does not affect descending inhibition from midbrain of nociceptive spinal neuronal discharges in the cat.

Discharges were recorded from spinal dorsal horn neurons in response to noxious skin heating (e.g. 50 degrees C). Repetitive electrical stimulation of the mesencephalic periaqueductal gray (PAG) inhibited these nociceptive discharges. In each of 9 experiments systemic administration of naloxone (1-3 mg/kg) did not affect this descending inhibition, arguing against involvement of endogenous opiates.

Animals↗

Encoding of graded noxious skin heating by neurons in posterior thalamus and adjacent areas in the cat.

Impulse discharges were recorded from 62 single units in the posterior thalamic and adjacent nuclei of the cat which received input from hindlimb cutaneous nerves. Noxious radiant heating (e.g., 50 degrees C for 10 sec) of the hindpaw excited 32% of the units. The magnitude of heat-evoked unit discharges was graded with the intensity of noxious heating. Such units had large cutaneous receptive fields spanning 2 or more limbs, and responded to strong mechanical stimuli (pressure, pinch). About half of the units responded also to light stimuli such as hair bending or touch.

Animals↗

Inhibition of spinal neuronal responses to noxious skin heating by stimulation of mesencephalic periaqueductal gray in the cat.

1. Discharges of lumbar dorsal horn neurons were evoked by noxious radiant skin heating, and inhibition of the heat-evoked responses by stimulation of the mesencephalic periaqueductal gray was investigated in N2O-anesthetized cats. 2. Thirty-seven units selected on the basis of receiving afferent C-fiber input from the posterior tibial and/or superficial peroneal nerves responded vigorously to 50 degrees C heating of the plantar surface of the ipsilateral hindpaw. All discharges were inhibited by periaqueductal gray stimulation (PAGS) at current strengths of 300--900 microA; the mean threshold for inhibition was 167 microamperemeter. The mean frequency of the inhibited discharge was 39% of the control response. 3. Effective PAGS sites were distributed throughout the ventral PAG bilaterally. Stimulus current-distance estimates indicate that small (0.5--1.2 mm diameter) volumes of tissue within the PAG were stimulated. 4. A monotonic relationship between temperature and unitary discharge was found for skin heating from threshold to about 50 degrees C. PAGS resulted in a decrease in the slope of the curve plotting discharge against temperature, without altering the threshold. 5. Inhibition of the heat-evoked discharges rarely outlasted the PAGS. 6. Possible neural substrates for descending inhibition and correlates with neural mechanisms of analgesia are discussed.

Animals↗

[Hydroxyethyl starch (HAS 450/0.7) in human plasma and liver. Course of concentration and histological changes].

In 12 patients 1,000 ml hydroxyethyl starch (Mw 450,000, degree of substitution 0.7) was infused intravenously. A liver biopsy was performed in 10 patients undergoing abdominal surgery 30 minutes to 28 days after the infusion. The liver tissue was investigated by light and electron microscopy. The plasma level of hydroxyethyl starch decreased to 4.8% of the initial concentration 28 days after the infusion (Anthron method). Single intracellular vacuoles were shown by electron microscopy 30 minutes after the end of infusion in Kupffer's cells only. However, 6 to 28 days after infusion intracellular vacuoles were demonstrated in parenchymal liver cells, Kupffer's cells, interstitial histiocytes and to a lesser degree in the cells of the small bile ducts. The pathogenic importance of the portracted elimination from the plasma and the liver storage is unknown.

Adult↗

[Inhibition in the spinal cord: a neuronal mechanism of hypalgesia produced by acupuncture (author's transl)].

Central nervous system mechanisms of nociception and pain were studied electrophysiologically in the spinal cord of cats. A great proportion of dorsal horn neurons respond to noxious skin stimuli, for instance to heating to 50 degrees C; such stimuli predominantly activate afferent C fibres. These spinal neurons participate in the transmission of nociceptive information to the brain. The heat-evoked discharges of dorsal horn neurons are effectively inhibited by repetitive electrical stimulation of large;, low-threshold cutaneous A fibres. The inhibition reaches its maximum effect after several minutes of nerve stimulation, and declines at a slow rate after the end of stimulation. This long-term suppression is considered to be a neuronal mechanism underlying hypalgesia produced in man e.g. by acupuncture and by transcutaneous nerve stimulation.

Acupuncture Therapy↗