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Biomedical subjects

M Michaelis

Publications and source records attributed to M Michaelis.

At least 37 records · Page 2Linked to original sources
PubMed1998

Inflammatory mediators sensitize acutely axotomized nerve fibers to mechanical stimulation in the rat.

Many axotomized myelinated as well as unmyelinated cutaneous nerve fibers are sensitive to mechanical stimuli applied to the cut nerve end within a few hours after nerve lesion. Here we investigated the influence of inflammatory mediators on this ectopic mechanosensitivity after cutting and ligating the sural nerve in anesthetized rats. Neural activity was recorded from single axons in filaments teased from the sural or sciatic nerve proximally to the lesion site 2-33 hr after axotomy. Using calibrated von Frey hairs (1.0-128.5 mN), 30 sec trains of phasic stimuli were applied to the cut nerve end immediately before and after local application of a mixture of inflammatory mediators [inflammatory soup (IS), consisting of bradykinin, 5-HT, prostaglandin E2, histamine (all 10 microM), and K+ 7 mM, pH 7.0] for 2 min. Before as well as after IS application, von Frey thresholds were significantly lower in myelinated (A) fibers than in unmyelinated (C) fibers. IS application enhanced the ectopic mechanical excitability, as expressed in reduced von Frey thresholds and increased response magnitudes, of most severed mechanosensitive C fibers (77%) and some mechanosensitive A fibers (46%). The sensitization lasted for 10-40 min after a 2 min IS application. Additionally, among axotomized nerve fibers unresponsive to probing of the nerve lesion site before IS application, 1 of 63 (1.6%) A and 3 of 106 (2.8%) C fibers became mechanosensitive immediately after IS application. The results indicate that after axotomy, inflammatory processes augment touch-evoked ectopic activity in lesioned sensory nerve fibers. Because many affected afferents are presumably of nociceptive function, their enhanced neural barrage may contribute to neuropathic pain states.

Action Potentials↗
PubMed1998

[Sympathetic nervous system and pain: pathophysiological mechanisms].

Sympathetic postganglionic neurons may be involved in the generation of pain, hyperalgesia and neurogenic inflammation under pathophysiological conditions. Experiments on animal models show that two categories of influence of the sympathetic neuron on afferent neurons can be distinguished and this distinction seems to be related as to whether sympathetic-afferent coupling develops after nerve lesion or after tissue trauma with inflammation. (1) Peripheral nerve lesion generates plastic changes of the afferent and sympathetic postganglionic neurons. This may lead to chemical coupling between sympathetic and afferent neurons which may entail activation and/or sensitization of primary afferent neurons by the sympathetic neurons. The mediator is probably noradrenaline and the afferent neuron expresses or upregulates functional adrenoceptors. The coupling may occur at different sites of the primary afferent neuron, e. g., at the lesion site, remote from the lesion site in the dorsal root ganglion or between nonlesioned sympathetic and afferent neurons which show collateral sprouting. The biochemical signals which trigger these changes probably are neurotrophic substances and their receptors which are synthesized by the peripheral neurons, Schwann cells and other cells in response to the peripheral lesions. (2) Sympathetic nerve terminals in peripheral tissues may serve as mediator elements in hyperalgesia and during inflammation following tissue trauma without nerve lesion. This function is largely independent of activity in the sympathetic neurons and independent of vesicular release of transmitter substances. The signals are probably synthesized and released from the sympathetic terminal or in association with it and belong to the prostaglandins (probably PGE(2) or PGI(2)). Furthermore, nerve growth factor (NGF) has a hyperalgesic action in inflammation which is at least in part dependent on the sympathetic nervous system.

English Abstract↗
PubMed1998

[Occupational spinal diseases in employees of nursing services--epidemiological and legal insurance aspects (III). 3: Intervertebral disk-induced diseases of the lumbar spine in health care employees--expert assessment and prevention].

Due to spine-loading activities nursing professionals have a relatively high incidence/prevalence of low back pain. As lumbar disc disorders can be regarded as occupational diseases (since January 1993, occupational disease BK 2108, normally more than 10 years of exposition, lumbar disc disorders with pain and reduced motility) international literature is reviewed. Own results of different prevalence-, case-control- and incidence studies (relative risk for lumbago sciatica/odds ratio for disc prolaps appr. 3-6 depending on age and occupational age) are presented. Finally the question of compensation and prevention of disc disorders is discussed.

Disability Evaluation↗
PubMed1998

[Current hepatitis B epidemiology in Germany].

Hepatitis B (HB) is the most common occupational hazard for health care workers. On the other hand 90% of the notified HB cases in Germany are observed among the general population (including other high-risk groups like i.v. drug abusers etc.). About 350 million persons all over the world are carriers of the hepatitis B virus (HBV). The availability of effective HB vaccines since 1982 made a control of HB possible. In this communication we report on epidemiological changes due to hepatitis B vaccination in a large university hospital in Germany. Health care workers and non-health care workers occupied at Freiburg university hospital were tested for HBV markers in 1984/85 (n = 4218), 1989/90 (n = 4081) and 1994/95 (n = 4022) during routine occupational health check-ups. Vaccinations were performed using a plasma-derived vaccine (1984/85) or a vaccine obtained by genetic engineering, respectively (1989/90, 1994/95). In 1984/85 prevalence of anti-HBs/HBc in German health care workers (12.4%) was 2.5 times higher than the one in non-health care workers (4.9%), in 1994/95 anti-HBs/HBc prevalence in both groups (4.4 vs. 4.5%) was comparable. On the other hand HBV carriage in persons occupied in professions without blood contact increased from 1984/85 (0.5%) to 1994/95 (1.1%). Therefore, the number of HBV carriers (ca. 1.1 millions) in Germany can be roughly estimated. Our data indicate a high degree of effectiveness of hepatitis B vaccines. Vaccination programme for the general population in accordance with German (STIKO) and WHO recommendations are necessary for the control of HBV infection.

Carrier State↗
PubMed1997

[Occupational diseases of the spine in health care professions-- epidemiologic and insurance aspects (I). 1. Review of internationally publicized studies].

Due to spine-loading activities nursing professionals have a relatively high incidence/prevalence of low back pain. As lumbar disc disorders can be regarded as occupational diseases (since January 1993, occupational disease BK 2108, normally more than 10 years of exposition, lumbar disc disorders with pain and reduced motility) international literature is reviewed. Own results of different prevalence-, case-control- and incidence studies (relative risk for lumbago sciatica/odds ratio for disc prolaps appr. 3-6 depending on age and occupational age) are presented. Finally the question of compensation and prevention of disc disorders is discussed.

Female↗
PubMed1997

Responses of distinct types of sympathetic neuron to stimulation of the superior laryngeal nerve in the cat.

Stimulation of afferents in the superior laryngeal nerve (SLN) leads to apnea and evokes reflexes in sympathetic neurons. It is not clear whether these reflexes are secondary to changes in the brainstem respiratory network or due directly to the afferent input on neurons belonging to central sympathetic pathways. To clarify this question, single thoracic preganglionic sympathetic neurons projecting into the cervical sympathetic trunk (CST) were classified as described previously and then tested for their responses to electrical stimulation of the superior laryngeal nerve (SLN) in chloralose-anesthetized, paralysed and artificially ventilated cats. SLN stimulation was performed with intensities sufficient to suppress central inspiratory activity detected by phrenic and recurrent laryngeal nerve recordings. Sympathetic neurons were tested under different levels of respiratory drive. Thirteen group I (putative muscle vasoconstrictor) neurons were mostly activated by SLN stimulation when respiratory drive was low, but depressed when it was high; this was due to the change in inspiration-related activity. Ten of eleven group II (putative cutaneous vasoconstrictor) neurons were depressed during SLN stimulation. This inhibition was independent of central respiratory drive. Inhibition also occurred in those neurons which predominantly discharged during postinspiration. Eight group III neurons which showed a discharge confined to inspiration were inhibited but mostly not silenced by SLN stimulation. Group IV (functionally unclassified) neurons either showed no response (n = 5) or were slightly inhibited (n = 2). The responses of group I neurons, but not the responses of group II and group III neurons, showed a significant positive correlation with those of systemic blood pressure. The observed responses corroborate the classification made previously. The results also demonstrate that the responses of sympathetic neurons to SLN stimulation are not merely due to the respiratory modulation of their activity, but rather consist of two components, one occurring independently of and the other secondary to, the changes in respiration.

Animals↗
PubMed1997

Algesics excite axotomised afferent nerve fibres within the first hours following nerve transection in rats.

The direct consequences of a peripheral nerve injury at the lesion site itself are often twofold: axons of afferent (and efferent) nerve fibres are transected and the tissue surrounding the nerve injury site is inflamed. Recent studies have shown that a few hours after nerve transection, axotomised myelinated (A) and unmyelinated (C) afferents may respond to mechanical and thermal stimuli applied to the cut nerve end. Here, 5-24 h after sural nerve ligation and transection we studied the ectopic excitability of axotomised cutaneous A and C fibres by chemical agents, most of which excite afferent terminals in skin. Topical application of bradykinin (BK; 10(-4) M) to the nerve stump excited 7.3% of all C fibres tested. Application of prostaglandin E2 (PGE2), a solution with increased proton concentration (pH 6.0) or a combination of inflammatory mediators ('inflammatory soup', containing histamine, 5-HT, BK and PGE2 (all 10(-5) M) at a pH of 7.0) activated 2.7-4.3% of all C fibres tested. Hypertonic saline solution (HS; 4.5%) and capsaicin, painful irritants, excited 8.3% and 5.0% of the C fibres, respectively. Among the axotomised A fibres tested, between 0.8% and 1.7% were excited by BK, PGE2, inflammatory soup (IS) or HS. Capsaicin and acid pH did not excite cut A fibres. In total, the number of chemically excited C fibres (50/547) significantly exceeded the number of activated A fibres (10/469). Local norepinephrine application (0.5-2.4.10(-3) M) did not activate A or C fibres (234 and 224 fibres tested, respectively). The results indicate that already during the first hours after transection of a peripheral skin nerve a significant proportion of axotomised afferents can be excited by topical chemical stimulation. This evoked activity is preferentially found in unmyelinated fibres, many of which have nociceptive functions. Chemically evoked discharges as described in the present study may therefore contribute to the induction of pain and paraesthesias in patients with peripheral nerve lesion when the injury site is inflamed.

Afferent Pathways↗
PubMed1997

[Spinal diseases in the nursing profession--a cross-sectional study].

A cross-sectional study on the profession-specific prevalence rates of back pain symptoms was conducted including N = 3332 nurses as the exposed group and N = 1720 office clerks as a control group. Only participants who had never changed from an exposed to an unexposed profession or vice versa, were included for the results presented here. Severity of symptoms was assessed, dividing into low back pain on the one hand, and lumbago-sciatica/sciatica on the other; frequency of pain episodes was measured using lifetime- and point-prevalence, in all these four combinations of severity and frequency the prevalence rates among nurses were clearly and significantly higher. Multivariate analyses revealed that profession is the most important risk factor among many others that were tested. Estimation of the prevalence rate for the heaviest symptom, the point-prevalence of lumbago-sciatica/sciatica, showed that about 4 out of 5 cases among nursing staff can be attributed to their profession. On the background of this high attributable risk the acceptance rate for LBP diseases of suspected occupational origin among nursing staff by statutory occupational health insurance bodies appears much too low.

Adult↗
PubMed1997

[Occupational medicine significance of hepatitis C in health care employees].

Transmission of Hepatitis C virus (HCV) is similar to the one observed with hepatitis B virus. The most important route of infection in health care personnel is by needlestick injury. In the course of a literature review 44 publications on HCV prevalence or incidence among hospital employees were studied and an overall transmission incidence of 2.2% was found. As none of the publications dealt with the problem of chronic Hepatitis C, 245 persons with elevated transaminases occupied Freiburg University Hospital were tested for HCV antibodies. 3 out of 82 non-medical professionals and 19 out of 163 health care workers were anti HCV positive (RR = 3.22; p < 0.05). Charwomen in medical departments, nurses and dentists had a higher relative risk than physicians and technical assistants. As no HCV vaccine is available the only way of HCV-prevention is compliance with universal precautions.

Adult↗
PubMed1996

Vesico-sympathetic reflexes in cat vasoconstrictor neurones supplying skin and skeletal muscle depend on the integrity of the sacral bladder afferents.

In anesthetized cats, distension of the urinary bladder induces powerful reflexes in postganglionic sympathetic neurones projecting to the hindlimb: muscle vasoconstrictor neurones (MVC) are excited and cutaneous vasoconstrictor neurones (CVC) are inhibited. We investigated these reflexes quantitatively before and after sacral rhizotomy. The reflex responses in MVC and CVC neurones were completely abolished after elimination of the pelvic afferent input demonstrating that these reflexes are generated exclusively by excitation of sacral bladder afferents. The activation of lumbar bladder afferents which are supposed to be able to elicit painful sensations did not contribute to vesico-sympathetic reflexes in MVC and CVC neurones.

Animals↗
PubMed1996

Prolonged injury discharge in unmyelinated nerve fibres following transection of the sural nerve in rats.

We studied the prolonged injury discharge in axotomized myelinated (A) and unmyelinated (C) nerve fibres within the first 15 min following sural nerve transection of the rat. Immediately after axotomy, 18% (22/122) of the C fibres generated action potentials, but none of 73 A fibres. This discharge ceased during the first 2 min after axotomy in most of the C fibres. The discharge frequency in the first 15 s after nerve cut varied between 0.3 and 7.2 Hz (mean 2 Hz) and decreased to a mean of 0.3 Hz 4 min after nerve lesion. C fibres displaying initial discharge frequencies of > or = 2 Hz ceased to generate action potentials significantly sooner than those with initial discharge frequencies of < 2 Hz.

Action Potentials↗
PubMed1996

Interactions of sympathetic and primary afferent neurons following nerve injury and tissue trauma.

Sympathetic post-ganglionic neurons may be involved in the generation of pain, hyperalgesia and inflammation under pathophysiological conditions. Two categories of influence of the sympathetic neuron on afferent neurons can be distinguished and this distinction seems to be related to whether the coupling between afferent and sympathetic neuron develops after nerve lesion or after tissue trauma with inflammation (Fig. 15): A. Peripheral nerve lesion generates plastic changes of the afferent and sympathetic postganglionic neurons, depending on the type of nerve lesion (e.g. complete, partial). Both afferent and post-ganglionic neurons exhibit degenerative and regenerative changes and unlesioned neurons may show collateral sprouting in the periphery as well as in the dorsal root ganglion. This reorganization of the peripheral neurons may lead to chemical coupling between sympathetic and afferent neurons. The coupling is responsible for sensitization and/or activation of primary afferent neurons by the sympathetic neurons. The mediator probably is norepinephrine, but other substances cannot be excluded. The afferent neuron expresses or upregulates functional adrenoceptors. The type of adrenoceptor involved is probably alpha 2. The coupling may occur at different sites of the primary afferent neuron, e.g. at the lesion site, remote from the lesion site in the dorsal root ganglion or between nonlesioned sympathetic and afferent neurons which show collateral sprouting. The biochemical signals which trigger these changes probably are neurotrophic substances, their receptors which are synthesized by the peripheral neurons, Schwann cells and other cells in response to the peripheral lesions. B. Sympathetic nerve terminals in peripheral tissues may serve as mediator elements in hyperalgesia and inflammation following tissue trauma without nerve lesion. Experiments show that these functions are largely independent of activity in the sympathetic neurons and independent of vesicular release of transmitter substances (such as norepinephrine). Sensitization of nociceptive afferents for mechanical stimuli and venular plasma extravasation in the synovium which are induced by the inflammatory mediator bradykinin are, at least in part, dependent on the sympathetic terminal. The signal to venules and afferent receptors is synthesized and released from the sympathetic terminal or in association with it. It is a prostaglandin (probably PGE2). Sympathetically mediated (neurogenic) inflammation and neurogenic inflammation mediated by afferents may interact reciprocally and enhance the inflammatory process as well as the sensitization of nociceptive afferents. Norepinephrine may also lead to sensitization of nociceptive afferents under inflammatory conditions. This sensitization is presumably mediated by alpha 2-adrenoceptors in the sympathetic varicosities and by a prostaglandin (probably PGI2) which is synthesized and released by or in association with the sympathetic varicosities.

Extremities↗
PubMed1996

Silent afferents: a separate class of primary afferents?

1. In recent years, fine sensory nerve fibres have been detected that are not excited by physiological stimuli, even at potentially tissue damaging intensities. These silent afferents are known to supply knee joint, skin and viscera; in the last case, silent afferents seem to be particularly numerous. 2. When an artificial inflammation is induced, many silent afferents develop spike activity, others remain quiescent. Silent afferents that do respond probably have a nociceptive sensory function. Under inflammatory conditions some silent afferents are sensitized to physiological stimuli, others are probably chemospecific. 3. Orthodromic activity in silent afferents may sum spatially and temporally in second order neurons with other nociceptive information and may thereby contribute to different pain states. Furthermore, there is evidence that the activation of chemospecific silent afferents may lead to sensitization of nociceptive dorsal horn neurons. 4. Some silent afferents probably contain neuropeptides that may be liberated under pathophysiological conditions, such as inflammation. 5. Whether certain pathological states can be exclusively attributed to the activation of silent afferents or whether silent afferents sustain the functions of 'conventional' nociceptors remains to be clarified.

Animals↗
PubMed1996

Thermosensitivity of acutely axotomized sensory nerve fibers.

1. Thermosensitivity of axotomized myelinated and unmyelinated fibers in the sural nerve was examined in anesthetized rats within 24 h after nerve ligation and transection. Activity in single fibers was recorded extracellularly from small filaments dissected from the nerve approximately 20-30 mm proximal to the lesioned site. Cold and warm stimuli were applied to the ligated and cut nerve end or 5-10 mm further proximal. 2. Among 871 unmyelinated fibers tested, 40 were excited by cooling of the cut and ligated nerve end (8-15 degrees C), 44 were excited by warming (35-65 degrees C), and 16 were both cold and warm sensitive. None of the 438 myelinated fibers investigated were activated by either cold or warm stimuli. 3. Cold- and warm-sensitive fibers responded in a graded fashion to thermal stimuli of variable temperatures. Between 11 and 30 degrees C, the responses of cold-sensitive fibers increased when the temperature was reduced. Responses of warm-sensitive fibers increased between 40 and 65 degrees C, when the temperature was increased. 4. Thermosensitive fibers displayed characteristic response profiles. Responses to cold stimuli were maximal at the beginning and decreased continuously to lower discharge frequencies as the stimuli were maintained. The stimulus-response curves to warm stimuli were bell-shaped and discharge frequencies were maximal after 5-15 s. 5. In some cold-sensitive fibers a spatial gradient of excitability emerged after axotomy. Maximal responses to isothermal stimuli were observed at the transection site, whereas the excitability declined when the thermal stimuli were applied 5 and 10 mm further proximal. 6. After axotomy, 190 unmyelinated fibers were exposed to cold and warm stimuli at two sites 5 and 10 mm proximal of the nerve stump, and 172 intact C fibers were stimulated at anatomically comparable sites along the nerve. No statistically significant difference was found between the prevalences of thermosensitivity of C fibers along their axons in these two groups (7 of 172 vs. 11 of 190). 7. In conclusion, some unmyelinated fibers can be ectopically excited by thermal stimuli within 24 h after nerve cut and ligation. This ectopically evoked activity may contribute to the generation of paresthesias, painful sensations, and associated changes following peripheral nerve lesion.

Afferent Pathways↗
PubMed1996

Sympathetic modulation of activity in rat dorsal root ganglion neurons changes over time following peripheral nerve injury.

1. We recorded from centrally connected axons isolated from the proximal stump of the sciatic nerve in intact rats and in rats whose nerves had been transected 4 days-6 mo previously. Afferent axons selected for study had spontaneous impulse activity that originated ectopically in dorsal root ganglia (DRGs) L4 and L5. The sympathetic supply of these DRGs was excited by repetitive electrical stimulation of ventral roots T13 and L1. We examined quantitatively changes in afferent ongoing firing evoked by sympathetic stimulation. Results are based on observations from 161 neurons in rats with sciatic nerve injury and from 58 neurons in control rats with intact sciatic nerves. Of these 219 neurons, 204 had myelinated fibers (A neurons) and 15 had unmyelinated fibers (C neurons), on the basis of measurements of conduction velocity. 2. In rats with nerve injury the majority of the spontaneously active neurons tested (95 of 161) responded to sympathetic stimulation with a change in ongoing firing frequency: 41 neurons exhibited a significant increase in discharge frequency that was often followed by suppression (28 of 41), and 54 neurons responded with a decrease in ongoing activity (simple suppression). In control rats, in contrast, only 1 of the 58 spontaneously active sensory neurons tested responded to sympathetic stimulation. 3. In A neurons, the response pattern changed systematically with time after sciatic nerve injury. At 4-22 days after nerve lesion, excitation was much more common than suppression. At 60-93 days, excitation and suppression occurred about equally. At 110-171 days, suppression was by far the more common response. 4. Of the 14 C neurons, 2 were excited by sympathetic stimulation (at 4-22 days postoperative) and 10 were suppressed (2 at 4-22 days, 8 at > 60 days). The only spontaneously active C neuron found in control rats was not affected by sympathetic stimulation. 5. The magnitude of responses in the three postoperative intervals investigated was similar. This was so for both the excitatory and the simple suppressive responses. The average latency between onset of stimulation and excitatory responses in afferent A fibers (approximately 10 s) was significantly less than the latency to simple suppressive responses (approximately 20 s). 6. The mean spontaneous firing rate of A neurons decreased with time after nerve lesion. No change was observed in C neuron activity. The mean firing rate of A neurons was significantly higher than that of C neurons 4-93 days after nerve lesion, but not later. In all three postoperative periods investigated, the mean rate of spontaneous activity was the same in A neurons that responded to sympathetic stimulation and A neurons that did not. 7. The results show that nerve injury triggers sympathetic-sensory coupling within rat DRGs. Excitatory coupling is preferentially present in the period shortly after nerve injury, and is subsequently replaced by suppressive coupling. This suggests that there is a gradual change in the underlying coupling mechanism.

Animals↗
PubMed1996

Adrenoreceptor subtype mediating sympathetic-sensory coupling in injured sensory neurons.

1. Teased axon recordings were made from 167 spontaneously active A beta- and A delta-afferents that ended in sciatic nerve end neuromas of 6-12 days standing. When challenged with a standard bolus of systemically applied adrenaline, 100 (60%) responded, either with an increase in baseline firing frequency (excitation, 96/100) or with a decrease (suppression, 4/100). 2. Experiments using receptor type-selective antagonists indicated that the adreno-sensitivity was mediated by alpha 2 adrenoreceptors in 65% of the afferents sampled, by alpha 1 adrenoreceptors in 13%, and about equally by alpha 1 and alpha 2 adrenoreceptors in approximately 10%. In the remaining 13%, neither type of antagonist blocked adrenaline-evoked excitation, at least not at the doses used. Both excitatory and suppressive responses were primarily sensitive to alpha 2 antagonists. 3. Experiments using receptor type-selective agonists substantiated the conclusion that sympathetic-sensory coupling at sites of nerve injury is mediated primarily by alpha 2 adrenoreceptors. 4. Recordings were also made from 14 afferent neurons with spontaneous ectopic discharge originating in dorsal root ganglia (DRGs) L4 and L5. The rats had undergone transection of the ipsilateral sciatic nerve 8-93 days previously. All neurons responded to systemic adrenaline and/or trains of activity evoked in postganglionic sympathetic efferents with either excitation or suppression. As in the neuroma endings, responses in the large majority of cases were blocked by alpha 2-selective, but not by alpha 1-selective adrenoreceptor antagonists. 5. The results indicate that sympathetic-sensory coupling, both at nerve injury sites and in axotomized DRG neurons, is mediated primarily by alpha 2 adrenoreceptors. In a minority of afferent neurons, however, it appears to be mediated by alpha 1 adreno-receptors or by both alpha 1 and alpha 2 adrenoreceptors. These functional results are consistent with receptor-type expression profiles from studies based on in situ hybridization and immunocytochemistry.

Adrenergic Agonists↗