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Biomedical subjects

M Zimmermann

Publications and source records attributed to M Zimmermann.

At least 343 records · Page 19Linked to original sources
PubMed1985

Tonic descending inhibition affects intensity coding of nociceptive responses of spinal dorsal horn neurones in the cat.

The supraspinal inhibitory control of lumbar spinal dorsal horn neurones was investigated in N2O-anaesthetized cats by reversibly blocking conduction in the spinal cord. Dorsal horn neurones selected for this study had convergent input from myelinated (A-) and unmyelinated (C-) fibres in the posterior tibial and/or superficial peroneal nerves of the hind limb. Virtually all of them could also be excited by noxious heating of the skin of the footpad region and by low intensity mechanical stimulation of the foot. Variation of the temperature of noxious radiant skin heating (40-56 degrees C, 10 sec in duration) resulted in graded responses of the neurones. The stimulus-response functions (SRF) were monotonic; in the majority of 32 cases they were linear. Neurones could be classified according to their maximum discharge frequency in response to skin heating into 22 weakly sensitive units (responses below 100 Hz at 50 degrees C) and 10 highly sensitive units (above 100 Hz). Responses outlasted the period of skin heating by seconds to minutes. A reversible conduction block of spinal axons by cooling a 15 mm cord segment (L1) with a thermode at 0 degrees C affected the responsiveness of the dorsal horn neurones in 12 of 15 cases. The maximum discharge frequency to a certain temperature of skin heating was increased during the spinal block. The duration of heat-evoked discharges was either not changed or increased during the spinal block. The SRF were reversibly displaced during the spinal blockade to higher discharge frequencies and lower threshold temperatures of skin heating. In 8 of 12 cases the change in the SRF was a nearly parallel shift, whereas in 4 units the increase of responsiveness had a complex effect upon the SRF. The decrease in the threshold to skin heating ranged up to 4.5 degrees C; the mean decrease was 2 degrees C. It is confirmed that in anaesthetized cats, nociceptive spinal neurones are subject to a tonically active descending inhibition, which is interrupted by local spinal cooling. The effect of the spinal block on the SRF of the neurones suggests that this tonic inhibition is similar to that produced by electrical stimulation in the lateral reticular formation of the brain-stem.

Animals↗
PubMed1985

[Late potentials: non-invasive detection in coronary disease and relation to severe ventricular arrhythmia].

Using high-gain amplification and signal averaging techniques, we tried to determine the clinical significance of ventricular late potentials (LP). 85 subjects were included in this study. No LP were detected in normal subjects (n = 25), nor in patients with various non-coronary cardiopathies who had presented ventricular tachycardia and/or fibrillation (VT/VF) (n = 10). LP were recorded only in patients with coronary heart disease (CHD) (n = 50). The prevalence of LP was 50% (9/18) in patients with a history of VT/VF (vs 12.5% = 4/32 in patients without such a history, p less than 0.02). We also found a prevalence of 50% (11/22) in patients with a ventricular aneurysm (vs 7.1% = 2/28 in patients without an aneurysm, p less than 0.01). The prevalence reached 80% (8/10) in patients with VT/VF and a ventricular aneurysm and it was only in this latter group of patients that the interval between the peak of the R wave and the end of ventricular electrical activity exceeded 100 ms (mean 111.2 +/- 12 ms, vs 50 +/- 8 ms in normal subjects, p less than 0.001). In all the cases submitted to surgery, the LP disappeared after resection of the aneurysm. In conclusion, LP, when of long duration, should be considered as a hallmark of malignant ventricular arrhythmias in patients with CHD.

Adolescent↗
PubMed1984

[Prognostic value of the late potentials of ventricular activation in coronary disease].

Identification of subsets of patients with coronary artery disease (CAD) who are prone to ventricular tachycardia or fibrillation (VT/VF) and to sudden arrhythmic death still represents one of the major problems in clinical cardiology today. Ninety-two patients with CAD were included in this prospective study, which was designed to assess the prognostic significance of ventricular late potentials (VLP) detected non-invasively using high-gain electrocardiography and signal averaging. The results clearly demonstrate that the presence of VLP increases the risk of VT/VF and the risk of sudden arrhythmic death in CAD patients. Because of its high sensitivity and non-invasiveness, high-gain electrocardiography should be included among the various electrophysiological investigations used to assess prognosis in CAD patients.

Adult↗
PubMed1984

Beta-adrenergic blocking agents: substituted phenylalkanolamines. Effect of side-chain length on beta-blocking potency in vitro.

The synthesis of a group of potential beta-blockers bearing a new 5-ethoxysalicylamide substituent on nitrogen is described. These compounds were tested for beta-adrenergic blocking potency in vitro and compared with analogous compounds bearing a tert-butyl group on nitrogen. The new N-substituent increased the beta-blocking potency substantially. In a series of five homologous compounds of the type Ar(CH2)nCHOHCH2NHR (R = 5-ethoxysalicylamide; n = 0-4), two maxima of beta-blocking potency were found for n = 0 and 2. Moreover, the carbon isostere of the corresponding (aryloxy)propanolamine still proved to be a very potent beta-blocker. The ether oxygen in the side chain is therefore not an absolute requirement for activity. Structure-activity relationships are discussed.

Adrenergic beta-Antagonists↗
PubMed1984

Inhibition in spinal cord of nociceptive information by electrical stimulation and morphine microinjection at identical sites in midbrain of the cat.

The descending inhibition of noxious heat-evoked spinal neuronal excitation produced by morphine (MOR) and electrical brain stimulation (EBS) given at identical sites in the midbrain was quantitatively studied in the anesthetized cat. Fifty-two dorsal horn units driven by electrical stimulation of the posterior tibial and/or superficial peroneal nerves at A- and C-fiber strength and responding to noxious radiant heating (50 degrees C) of the skin of the foot-or toepads were studied. All units also responded to mechanical skin stimuli and were located primarily in laminae IV-VI of the dorsal horn. MOR (10-20 micrograms) was administered at 23 different sites in the midbrain. MOR attenuated the heat-evoked responses of 14 of 18 dorsal horn units studied to a mean 43% of the control heat-evoked response when administered at 18 sites in and immediately surrounding the periaqueductal gray (PAG). MOR administered at four sites in the PAG failed to significantly attenuate spinal nociceptive responses. The 14 sites where MOR was efficacious were distributed throughout the PAG. The efficacy of the MOR-produced inhibition was not correlated significantly to the distance from the cerebral aqueduct for the 18 PAG sites examined nor was there any difference in the spinal inhibitory effects of MOR, whether administered dorsally or ventrally in the PAG. MOR also failed to affect spinal neuronal heat-evoked responses (n = 5) when administered at five sites in the reticular formation ipsilateral to the PAG. EBS at the same 23 sites where MOR was given and at 34 additional sites in the midbrain attenuated the heat-evoked responses of all but one dorsal horn unit studied (mean maximal inhibition to 35% of control). In the PAG, stimulation ventrally inhibited a significantly greater proportion (13/21, 62%) of heat-evoked spinal neuronal responses to less than or equal to 25% of the control heat-evoked response than did stimulation in the dorsal PAG (5/15, 33%). The efficacy of the stimulation-produced inhibition was not, however, correlated significantly to the distance from the cerebral aqueduct for the total 57 midbrain sites examined, the 23 sites at which MOR was also tested, or only those EBS sites in and surrounding the PAG (n = 44).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Basic concepts of pain and pain therapy.

Pain originating in the peripheral nervous system is based on the excitation of nociceptive afferent fibers, which are contained among A-delta- and C-fibers from skin, viscera, joints and muscles. Often, this excitation originates at the peripheral fiber ending, the nociceptor. Nociceptors are excited by strong stimuli, which may eventually become destructive. Nociceptor excitability is enhanced by endogenous chemical substances as occur, e.g., during inflammation. Some analgesic substances, e.g. acetylsalicylic acid, inhibit the synthesis of prostaglandins and related metabolites, which is thought to be a mechanism of peripheral analgesia. Some forms of chronic pain are due to pathophysiological conditions of peripheral axons. Neuralgic pain may be caused by prolonged compression of a nerve. Here, ectopic impulse generation at the site of compression is considered a mechanism of pain. In a nerve regenerating after trauma the sprouts are sensitive to mechanical and chemical influences and thus may produce abnormal discharges in the neuroma. Sympathetic influences might enhance excitability of sprouts in the neuroma. Excitation of nociceptors by the sympathetic nervous system probably also occurs in other situations of chronic pain, such as Sudeck's syndrome. Here, the chronic pain may be sustained by a positive feedback loop via somato-sympathetic reflexes (sympathetic reflex dystrophy). Similar mechanisms of positive feedback also occur in the skeletomotor system, where chronic pain conditions can be sustained by inappropriate muscle tone. In the central nervous system much of the information from the nociceptive afferent fibers is contained in the discharges of multireceptive neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1983

Phenol solutions differentially block conduction in cutaneous nerve fibers of the cat.

The action of phenol in Tyrode solution on nerve conduction has been investigated in vivo in the desheathed sural nerve of cats. A section of 8 mm of the nerve was exposed to phenol solution. At low phenol concentrations (0.05-0.125%) a reversible block of A- and C-fibers occurred. At higher concentrations (0.6-1%) a selective and persistent C-fiber block could be achieved. The size of the residual A-volley was between 50% and 81% when all C-fibers were blocked.

Animals↗
PubMed1983

[Non-invasive detection of late potentials of ventricular activation: identification and significance in coronary disease].

Using a high-amplification electrocardiograph with signal averaging, an attempt has been made to determine the prevalence of delayed potentials of ventricular activation (DPVA) in coronary heart disease (CHD) and their relation to ventricular tachycardia and/or fibrillation (VT/VF). No DPVA could be recorded in normal subjects (n = 25) or in patients with various cardiopathies with VT/VF but without CHD (n = 10). DPVA have been recorded only in patients with CHD (n = 50) (all patients having undergone ventriculography and coronarography). The prevalence of DPVA is 12.5% without VT/VF, 50% with VT/VF, and 80% when these arrhythmias are associated with the presence of a ventricular aneurysm. The duration of the DPVA is also important, since it is only in the group with VT/VF and with aneurysm that the R-EVEA duration (interval between the peak of the R wave and the end of electrical ventricular activity) exceeds 100 ms. DPVA disappeared in all the cases after aneurysmectomy. The DPVA, when of long duration, can be considered a hallmark of serious ventricular arrhythmias in patients with CHD and a ventricular aneurysm.

Action Potentials↗
PubMed1983

Persisting selective block of unmyelinated fibers in cutaneous nerves of the cat by distilled water.

Experiments were done in vivo on the sural nerve of the cat's hindlimb. The nerve was desheathed for a length of 8 mm and superfused by Tyrode solution or distilled water. Electrical stimulation and recording was used to evaluate conduction block of nerve fibers. Irrigation with distilled water for periods of 3-5 min caused a persisting selective block of conduction in C-fibers while most of the A-fibers were unaffected. Recovery of the C-fibers never occurred during the time of observation (up to 130 min).

Animals↗
PubMed1983

Characteristics of spinal dorsal horn neurons after partial chronic deafferentation by dorsal root transection.

Unilateral transections of 1-3 lumbar dorsal roots were performed in 13 adult cats to investigate the effect of partial deafferentation on dorsal horn neurons. Eleven to 45 days after deafferentation various parameters of spontaneous and evoked activity of 169 neurons were measured and compared to the data of 168 neurons from previous experiments recorded under identical experimental conditions except that these animals had not been deafferented. Eighty-six of the units encountered were located in the segment of transected dorsal root(s) and 82 in the caudally adjacent segment. No significant differences could be observed in the functional properties of these two samples of units. Most parameters measured indicate that either no change at all in responsiveness or signs of decreased excitability occurred in the partially deafferented neurons compared to units recorded in control animals. Discharges evoked by noxious skin heating indicate a linear relationship between discharge frequency and skin temperature. This kind of encoding curve could also be measured during a reversible cold block of the spinal cord at segment L1. The mean encoding curves before and during spinal blockade were not different in deafferented compared to corresponding curves measured in control animals. The only finding that could be interpreted as an indication for increased excitability of partially deafferented neurons was that the mean frequency of spontaneous discharges of a subsample of heat-sensitive neurons was higher in deafferented compared to control animals. Possible mechanisms are discussed.

Action Potentials↗
PubMed1983

Effects of gamma-aminobutyrate and bicuculline on primary afferent depolarization of cutaneous fibres in the cat spinal cord.

The excitability of single cutaneous primary afferent fibres (sural nerve) was tested by focal stimulation in the dorsal horn of the cat spinal cord, and recording the antidromically conducted action potential in the peripheral nerve. To induce primary afferent depolarization, which is an expression of presynaptic inhibition, the superficial peroneal nerve was stimulated. The primary afferent depolarization was measured as the concomitant excitability change in the antidromically excited sural fibre. This primary afferent depolarization was reduced by 32% during microelectrophoretic release of bicuculline methochloride near the microstimulation electrode in the dorsal horn. Microelectrophoresis of gamma-aminobutyrate increased excitability in sural nerve fibres which correlated with the primary afferent depolarization induced by stimulation of the superficial peroneal nerve. The results suggest a possible role for gamma-aminobutyrate in presynaptic inhibition of cutaneous afferent fibres in the cat.

Afferent Pathways↗
PubMed1983

Quantitative comparison of inhibition in spinal cord of nociceptive information by stimulation in periaqueductal gray or nucleus raphe magnus of the cat.

The descending inhibition of spinal neuronal responses by focal electrical stimulation in the periaqueductal gray (PAG) or nucleus raphe magnus (NRM) was quantitatively studied and compared in the anesthetized, paralyzed cat. All 60 dorsal horn neurons studied were driven by electrical stimulation of hindlimb cutaneous nerves at strengths supramaximal for activation of A-alpha,delta- and C-fibers, and 52 also responded to noxious radiant heating (50 degrees C, 10 s) of the skin of the foot- or toepads; 8 units had receptive fields in the hairy skin of the hindlimb. All neurons studied also responded to mechanical stimuli; recording sites were located in laminae I-VI of the dorsal horn. The inhibition of spinal neuronal heat-evoked responses by stimulation in the PAG or NRM differed quantitatively when examined on the same spinal neurons. Inhibition of heat-evoked spinal neuronal responses occurred at a lower threshold of stimulation in the NRM than in the PAG. The mean intensity of stimulation in the NRM producing an attenuation to 50% of the control 50 degrees C heat-evoked response was significantly lower than the mean intensity of stimulation in the PAG producing a 50% attenuation of the same spinal units. The mean magnitude of inhibition produced by stimulation in the NRM was significantly greater than that produced on the same spinal units by the same intensity of stimulation in the PAG. However, stimulation in the NRM and PAG produced the same mean percent change in inhibition per 100-microA increase in the intensity of stimulation. Thus, the slopes of the recruitment of descending inhibition from the PAG and the NRM as a function of increasing intensities of stimulation are the same; the lines of recruitment of inhibition are parallel. When examined on the same dorsal horn units, stimulation in the PAG influenced their intensity coding to graded noxious heating of the skin differently than did stimulation in the NRM. The responses of the class 2 and class 3 spinal units examined to increasing temperatures of heat applied to the skin was a monotonic linear function throughout the temperature range studied (42-50 degrees C). Stimulation in the PAG decreased the slope of the stimulus-response function (SRF) without affecting unit thresholds of response, thus influencing the gain control of nociceptive transmission in the dorsal horn. Stimulation in the NRM produced a parallel shift to the right of the SRF, influencing the set point and threshold of response.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Inhibition of spinal nociceptive information by stimulation in midbrain of the cat is blocked by lidocaine microinjected in nucleus raphe magnus and medullary reticular formation.

The organization in the brain stem of descending inhibitory control of spinal nociceptive information was studied in anesthetized, paralyzed cats by quantitatively evaluating the effects of reversible blocks produced by lidocaine microinjected in the medial and/or lateral medulla. Spinal neuronal inhibition produced by stimulation in the nucleus raphe magnus (NRMS) was compared to the inhibition of the same dorsal horn neurons produced by stimulation 2 mm lateral in the medullary reticular formation (MRFS). When the inhibition produced by NRMS and/or MRFS was blocked by lidocaine microinjected in those medullary sites, the efficacy of spinal neuronal inhibition produced by stimulation in the midbrain periaqueductal gray (PAGS) and 4 mm lateral in the reticular formation (LRFS) was evaluated and compared with the inhibition produced before the intramedullary microinjection of lidocaine. All 32 spinal dorsal horn neurons studied responded to hindlimb cutaneous nerve stimulation at strengths supramaximal for activation of A-alpha,delta- and C-fibers, to mechanical stimuli applied to the skin, and 27 also responded to noxious radiant heating (50 degrees C, 10 s) of the skin of the foot- or toepads (5 units had receptive fields in the hairy skin of the hindlimb). The noxious heat-evoked responses of all units studied were inhibited by NRMS or MRFS. The mean threshold currents for spinal inhibition, the mean maximal inhibition produced, and the mean stimulation currents producing an attenuation to 50% of the control response to 50 degrees C skin heating did not differ between NRMS and MRFS. When quantitatively compared on the same spinal units, NRMS produced the same mean magnitude of inhibition as the same intensities of MRFS, and both NRMS and MRFS produced the same mean percent increment in inhibition per 100-microA increase in the intensity of brain stimulation. The responses of the spinal units studied to graded noxious heating of the skin was a monotonic linear function throughout the temperature range employed (42-50 degrees C). MRFS shifted this stimulus response function (SRF) to the right, raising significantly the threshold of response a mean 2.2 degrees C to noxious heating of the skin without significantly affecting the slope of the SRF. MRFS reduced the number of discharges of spinal units evoked by electrical A-alpha,beta-fiber stimulation of hindlimb cutaneous nerves in 4 of 10 units studied. NRMS similarly inhibited the A-alpha,beta-fiber-evoked responses of two of the same four units affected by MRFS but also affected two of the remaining six units not affected by MRFS.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1982

[Pain in the cancer patient--mechanisms, diagnosis, therapy].

Pain is the most relevant symptom for many cancer patients, therefore treatment is of great importance. Improved knowledge about the mechanisms involved in cancer pain might help to improve therapy. Peripherally acting analgesics should be used when inflammatory mechanisms contribute to the pain (e.g., prostaglandin release). Analgesics acting in the central nervous system (opiates) can be given over longer periods via the oral route; the risk of side effects then is fairly low. Analgesics have to be administered at regular intervals. Severe states of pain can be managed with peridural administration of opitates.

Analgesics↗
PubMed1982

Electrical stimulation of the human brain.

Electrical stimulation of the human brain is one of the most exciting chapters in the story of experimental neurobiology. Since the first reported case of brain stimulation in a patient, by Bartholow in 1874, much progress has been made in this field. Today's methods of stimulation are much more subtle, and sophisticated methods for the assessment of the patient's experiences are used, as is shown by the following papers. The object of this issue is to provide an overview of the recent work in this field and to outline the influences it has, or should have, on our functional concepts of the human brain.

Brain↗