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Siegfried Mense

Publications and source records attributed to Siegfried Mense.

16 recordsLinked to original sources
PubMed2006

Effects on c-Fos expression in the PAG and thalamus by selective input via tetrodotoxin-resistant afferent fibres from muscle and skin.

Nociceptive information from skin and muscle is differently processed at many levels of the central nervous system. However, with regard to nociceptive input from muscle to the thalamus, only few data are available. Here, we investigated the c-Fos expression in the thalamus and the periaqueductal grey matter (PAG) induced by electrical stimulation of tetrodotoxin-resistant (TTX-r), presumably nociceptive, afferent fibres. In addition, a comparison between the effects of TTX-r input from muscle and skin was made. In anaesthetised rats, a skin or a muscle nerve was stimulated electrically for 1h at an intensity supramaximal for unmyelinated fibres. To block TTX-sensitive afferents, TTX was applied to the sciatic nerve. c-Fos was visualized using DAB immunohistochemistry. Here we report for the first time that in the PAG and medial thalamus, the main effect of TTX-r input from muscle was a reduction in c-Fos expression, and that in some thalamic nuclei (e.g. posterior, reuniens, and central medial nuclei), significant differences in the number of c-Fos-positive cells were found after muscle and cutaneous input, respectively. The thalamic regions with the strongest effects of muscle input were the VL bilaterally and the VPL contralaterally (increase in c-Fos expression) as well as the rhomboid nucleus (decrease in c-Fos expression).

Afferent Pathways↗
PubMed2005

Excitatory and modulatory effects of inflammatory cytokines and neurotrophins on mechanosensitive group IV muscle afferents in the rat.

In inflamed tissue--including skeletal muscle--the concentrations of cytokines and neurotrophins are known to increase. However, nothing is known about a possible contribution of these agents to muscle pain and hyperalgesia. The present study investigated acute effects of cytokines and neurotrophins on response properties of slowly conducting muscle afferents. In anaesthetised rats, the impulse activity of single mechanosensitive group IV fibres innervating the gastrocnemius-soleus muscle was recorded and tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), nerve growth factor (NGF), or brain-derived neurotrophic factor (BDNF) were injected into the muscle. Changes in the mechanosensibility of the endings following administration of the agents were tested with repeated pressure stimuli of defined forces. A low mechanical threshold in the innocuous range was found in 44.4% of the units tested, 55.6% required strong, potentially tissue-damaging pressure stimuli for activation. NGF excited only units that had a high mechanical threshold, while IL-6 was a stimulant for low-threshold mechanosensitive units only. TNF-alpha and BDNF did not excite group IV units but had a desensitising action: after TNF-alpha or BDNF, the response magnitudes to pressure stimuli decreased significantly. The data indicate that cytokines and neurotrophins influence the impulse activity and mechanosensitivity of group IV muscle afferent units. These effects could be of functional significance when the agents are released from muscle cells under pathophysiological circumstances.

Action Potentials↗
PubMed2005

The possible role of the NO-cGMP pathway in nociception: different spinal and supraspinal action of enzyme blockers on rat dorsal horn neurones.

In the literature, the pro- or antinociceptive effects of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) are discussed controversially. Our laboratory and others have reported that in the spinal cord a local lack of NO has an excitatory action on the ongoing (background) activity of dorsal horn neurones. Here, we tested the hypothesis that this effect of NO is mediated by cGMP and that part of the controversy is due to differences in the spinal and supraspinal actions of both compounds. In anaesthetised rats, impulse activity of lumbar dorsal horn neurones was recorded, and blockers of NO- and cGMP-synthesis, as well as the phosphodiesterase 5 (PDE5) inhibitor sildenafil (which increases the cGMP level), or 8-Bromo-cGMP (a membrane permeable cGMP analogue) were administered spinally or supraspinally. Topical superfusion of the spinal cord with a blocker of the guanylyl cyclase (ODQ) to reduce the cGMP level led to an increase in background activity of nociceptive lumbar dorsal horn neurones similar to that caused by l-NAME, a blocker of the NO synthase. Spinal superfusion with sildenafil or 8-Bromo-cGMP had no excitatory effect. In contrast, injections of sildenafil or 8-Bromo-cGMP into the third cerebral ventricle caused an increased background activity in lumbar dorsal horn neurones, while l-NAME and ODQ were ineffective. The results show that at the spinal level, a lack of cGMP and NO has an excitatory action on dorsal horn neurones, whereas supraspinally an elevated level of cGMP is excitatory.

Action Potentials↗
PubMed2005

Interaction between neurotransmitter antagonists and effects of sacral neuromodulation in rats with chronically hyperactive bladder.

OBJECTIVE: To investigate to what extent antagonists of spinal neurotransmitters interact with the effects of sacral neuromodulation in a rat model of a chronically hyperactive urinary bladder. MATERIALS AND METHODS: In female rats the urinary bladder was instilled with turpentine oil 2.5% to induce cystitis. After surviving for 10 days the rats were anaesthetized with urethane, the bladder catheterized and connected to a pressure transducer. Stimulating electrodes were placed in the sacral foramina bilaterally. The spinal cord was exposed by a laminectomy, and a small pool was placed on the cord for intrathecal administration of neurotransmitter antagonists. Sacral neuromodulation was applied before and after administering the antagonists. The antagonists used were: memantine, an antagonist for N-methyl-D-aspartate (NMDA) receptors; CNQX, an antagonist for non-NMDA receptors, and L-NAPNA, a blocker of nitric oxide synthase. RESULTS: With no electrical neuromodulation, memantine and L-NAPNA abolished the cystitis-induced bladder contractions for approximately 4 and approximately 37 min, respectively. The effect of CNQX was similar to that of artificial cerebrospinal fluid. Electrical sacral modulation with no antagonists also transiently abolished the bladder contractions; at the highest intensity used, the pause was 2-3 min. Superfusion of the spinal cord with CNQX reduced this effect of neuromodulation significantly, whereas memantine had no influence, and L-NAPNA increased the neuromodulation-induced pause. CONCLUSIONS: The results suggest that non-NMDA receptors are involved in the effects of sacral neuromodulation, whereas NMDA receptors appear to have no role. Nitric oxide is essential for maintaining the chronic hyperactive state of the urinary bladder.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2004

Painful and non-painful pressure sensations from human skeletal muscle.

Painful and non-painful pressure sensations from muscle are generally accepted to exist but the peripheral neural correlate has not been clarified. The aim of the present human study was to assess the non-painful and painful pressure sensitivity with (1) anaesthetised skin, and (2) anaesthetised skin combined with a block of large diameter muscle afferents. The skin was anaesthetised by a topically applied anaesthetic cream and later lidocaine was administrated subcutaneously. The pressure sensitivity was assessed quantitatively by computer-controlled pressure stimulation on the anterior tibial muscle. Thresholds to detection, pain and pain tolerance were assessed. In the first experiment, computer-controlled needle insertion depths evoking touch and pain sensations were used to assess the efficacy of cutaneous anaesthesia. Touch and pain sensations evoked during needle insertions were found to be superficial in intact skin but when anaesthetised, touch sensation was occasionally evoked at depths related to penetration of the fascia. With the skin completely anaesthetised to brush and von Frey hair pinprick stimulation, skin indentation with the strongest von Frey hair caused a sensation described as a deep touch sensation. Simultaneously, pressure detection and pain thresholds increased but it was still possible to elicit non-painful and painful pressure sensation in all subjects. In a second experiment, a differential nerve block of group I and II afferent fibres was obtained by full-leg ischaemia simultaneously with cutaneous anaesthesia. The efficacy of the tourniquet block was continuously assessed by a battery of somatosensory tests (heat, brush, vibration, electrical and movement detection) applied at the foot simultaneously with pressure stimulation on the anterior tibial muscle. After 20 min of ischaemia, group II afferent fibres mediating the sensations of movement detection, vibration and brush on the foot was blocked but the heat pain threshold was not affected. In this condition (anaesthetised skin and block of group I and II fibres from deep tissue) a pressure sensation was evoked in 70% of subjects although the pressure detection threshold was increased. The pressure pain sensitivity was decreased, which, however, might indicate a partial block of group III and IV muscle afferents. In a third experiment, the tactile sensations elicited by electrical stimulation of the tibialis anterior muscle and skin at the lower leg were significantly decreased after 20 min of ischaemia, validating the blocking effects of group I and II nerve fibres. The present data show a marginal contribution of cutaneous afferents to the pressure pain sensation that, however, is relatively more dependent on contributions from deep tissue group III and IV afferents. Moreover, a pressure sensation can be elicited from deep tissue probably mediated by group III and IV afferents involving low-threshold mechanoreceptors.

Adult↗
PubMed2004

Acidic pH and capsaicin activate mechanosensitive group IV muscle receptors in the rat.

Strenuous exercise of muscle as well as inflammation and ischaemia are associated with tissue acidosis. However, so far, nothing is known about the sensitivity to hydrogen ions of slowly conducting muscle afferent units. The study investigated if acid-sensing ion channels, e.g. the polymodal acid/capsaicin-sensitive vanilloid receptors, were present on unmyelinated (group IV) muscle afferent units of the gastrocnemius-soleus muscle of the rat. Intramuscular injections of acidic phosphate buffer pH 6 excited 56.0% of the group IV units. A similar proportion (54.29%) was activated by capsaicin (655 microM). Tests of the same unit with both adenosine triphosphate at neutral pH (ATP, 7.6 mM; pH 7.4) and acidic phosphate demonstrated that most acid-sensitive units were also excited by ATP at neutral pH. The data show that (1) a high proportion of group IV muscle receptors are responsive to an increased extracellular hydrogen ion concentration, and (2) a subpopulation of these units are sensitive to both acidic pH and ATP.

Action Potentials↗
PubMed2004

A rat model for studying effects of sacral neuromodulation on the contractile activity of a chronically inflamed bladder.

OBJECTIVE: To develop an animal model in which the effects of electrical stimulation of the sacral nerves (sacral neuromodulation) on a chronic hyperactive urinary bladder can be studied. MATERIALS AND METHODS: In female rats the urinary bladder was instilled with mustard oil (0.4%); after 10 days the animals were anaesthetized with intraperitoneal urethane, the bladder catheterized and connected to a pressure transducer. Stimulating electrodes were placed into the sacral foramina bilaterally. The intensity and duration of sacral electrical stimulation was varied systematically to determine the effects of the sacral neuromodulation on bladder contractions. RESULTS: The main effect of the neuromodulation was an increase in the interval between contractions, i.e. during and for some time after the stimulation the contractions were completely abolished. The duration of the pause increased with the intensity and duration of stimulation. After the contractions had reappeared the frequency of contractions was reduced for a long period. In animals with chronic cystitis the effects of neuromodulation tended to be stronger (the pauses were longer) than in control animals with an intact bladder, but only in one test (increase of pause length with stimulus duration) was the difference statistically significant. CONCLUSIONS: The results show that this animal model is suitable for studying the effects and mechanisms of sacral neuromodulation on a chronic hyperactive urinary bladder.

Animals↗
PubMed2003

Pathophysiological activity in rat dorsal horn neurones in segments rostral to a chronic spinal cord injury.

As a sequel of complete spinal cord injury (SCI), patients often develop chronic pain which is perceived at or just below the level of the lesion. Likewise, in animal models of SCI, spontaneous and evoked pain-related behaviour can be observed. In the present study, the hypothesis was tested that pain related behaviour after SCI in animals is at least partly due to neuronal hyperactivity in spinal segments rostral to the site of injury. In rats with a chronic transected spinal cord, the impulse activity of single dorsal horn neurones was recorded in two locations: (1) directly rostrally adjacent to the lesion, and (2) 2-3 segments more rostrally. Cord transections were made either at the thoracic or at the lumbar level. Sham-operated rats and rats which underwent no surgical interventions served as controls. Compared with both controls, in SCI animals the background activity of the neurones had a significantly higher level in both series. Often the activity showed a pathophysiological altered discharge pattern. Following SCI, there was a general increase in the mechanical responsiveness of neurones that were recorded 2-3 segments rostrally to the lesion. The results suggest that neuronal hyperactivity in spinal segments just rostral to the lesion may contribute to chronic spontaneous SCI pain. Further, there is some indication that the allodynia perceived in body regions near and above the level of the SCI may be due to increased responsiveness to weak stimuli of neurones located more rostrally to the lesion.

Animals↗
PubMed2003

Adenosine triphosphate as a stimulant for nociceptive and non-nociceptive muscle group IV receptors in the rat.

For cutaneous and articular nociceptors, adenosine triphosphate (ATP) has been shown to be an effective stimulant. The aim of present study was to find out if among muscle afferents ATP-sensitive group IV receptors are present, and if differences in ATP-responsiveness existed between nociceptive and non-nociceptive units. Single fibre activity was recorded from group IV afferents innervating the rat gastrocnemius-soleus muscle. Using mechanical stimuli the fibres were classified as nociceptive or non-nociceptive ones. ATP was injected intramuscularly into the receptive field of the fibre. Results were: (1) ATP at a concentration that is present in muscle cells elicited excitations in 67% of the fibres; (2) ATP excited both nociceptive and non-nociceptive receptors; and (3) the acidity of the ATP solution was not an important factor for the ATP effect.

Action Potentials↗
PubMed2003

The pathogenesis of muscle pain.

Nociceptive nerve endings in muscles and other tissues are equipped with a multitude of receptor molecules for endogenous pain-producing and sensitizing agents. Particularly interesting molecules are the purinergic receptors, which can be activated by adenosine triphosphate (ATP), and the vanilloid receptor, which is sensitive to protons (low pH). The purinergic receptors are activated by tissue damage because cell necrosis is associated with the release of ATP. A low pH is present in many pathologic conditions such as ischemia and inflammation. At the spinal and medullar level, painful muscle lesions induce marked neuroplastic changes that result in hyperexcitability and hyperactivity of nociceptive neurons. This central sensitization is the basis for the spontaneous pain and hyperalgesia of patients. The transition from acute to chronic muscle pain is complete when the initially functional changes are transformed into structural ones. Patients with morphologic alterations in their nociceptive system are difficult to treat because the changes need time to normalize.

Animals↗
PubMed2003

Experimental pain by ischaemic contractions compared with pain by intramuscular infusions of adenosine and hypertonic saline.

Deep tissue pain can be related to reduced muscle blood flow, which comprises the metabolic demand under muscle work. The tissues and receptors involved in nociception after ischaemic muscle contractions are not known. The concentration of adenosine is increased after ischaemic contractions and might act as an algesic substance. In 15 subjects, adenosine, hypertonic saline (algesic), and isotonic mannitol (placebo) were infused into the tibialis anterior muscle and compared with the pain caused by ischaemic contractions. The muscle pain intensity (visual analogue scale; VAS), distribution, and quality were assessed. Pressure pain thresholds were recorded to assess the deep tissue sensitivity. Adenosine did not induce more pain than the placebo. The maximal VAS score after hypertonic saline and ischaemic contractions was higher compared with adenosine/placebo infusions. The duration and area of pain were significantly increased after hypertonic saline infusions compared with ischaemic contractions. Higher scores on the McGill pain questionnaire were given to the "stabbing", "burning", "heavy", and "exhausting" word categories after ischaemic contractions, and "cramping" was rated higher during hypertonic saline-induced muscle pain compared with ischaemic contractions. During hypertonic saline infusions, the pressure pain threshold was decreased compared with before and immediately after the pain had vanished. The present study shows that pharmacological levels of adenosine in skeletal muscle did not induce pain. Excitation of muscle nociceptors by hypertonic saline evoked hyperalgesia, larger areas of pain, and a different quality of pain compared with ischaemic contractions, suggesting that the pain after ischaemic contractions is mediated by other populations of nociceptors in muscle and/or other tissues than excited by hypertonic saline.

Adenosine↗
PubMed2002

Tetrodotoxin block of A-fibre afferents from skin and muscle - a tool to study pure C-fibre effects in the spinal cord.

The properties of tetrodotoxin (TTX)-resistant C-fibre afferents of the dorsal roots were tested in Sprague-Dawley rats. Dorsal roots (L4-L6) were blocked with TTX (0.5-1 micro M) and the amplitude of the first response of the dorsal horn superficial interneurones (cord dorsum potential, CDP) to electrical stimulation of peripheral C-fibres in combination with natural noxious stimulation was taken as measure for intact conductivity of different kinds of noxious input by means of the C-fibre refractory period. After blockade of dorsal roots with TTX, formerly masked CDPs from muscle C-fibre afferents were uncovered. Noxious pressure to the gastrocnemius soleus muscle belly and noxious pinch to the calcanean tendon proved to be TTX resistant and therefore was propagated centrally. For cutaneous heat nociceptors it could also be shown that conductivity was intact after blockade of the dorsal roots with TTX. However, we could not exclude the TTX resistance of non-nociceptive receptors of muscle or skin. Nevertheless, blockade of afferents with TTX together with suitable stimulation techniques proves to be a reliable method to investigate central effects from C-fibre afferents without contaminating effects from A-fibres in the rat.

Anesthetics, Local↗
PubMed2002

Rats with chronic spinal cord transection as a possible model for the at-level pain of paraplegic patients.

Patients with complete spinal cord injury (SCI) often suffer from chronic pain which is perceived around the segment of the lesion. The present study tests the hypothesis that chronic SCI pain is due to pathophysiological neuronal activity in the spinal segment just rostral to the SCI. In an animal model with complete chronic SCI, the impulse activity of single dorsal horn neurones was recorded in the segment rostral to the lesion. Following SCI, the neurones exhibited a higher background activity. Some neurones showed an abnormal type of activity which was not present under control conditions. The results support the hypothesis that increased and altered background activity just rostral to the lesion contributes to chronic at-level pain of paraplegic patients.

Animals↗
PubMed1999

Mechanisms underlying the pathogenesis of urinary bladder instability - new perspectives for the treatment of reflex incontinence.

The urine storage ability of the urinary bladder is markedly impaired following inflammation of the urinary bladder and spinal cord injury because of a hyperexcitability of micturition reflexes. Using two rat models of inflammation-induced bladder overactivity and detrusor hyper-reflexia following spinal cord injury we investigated changes in the neuronal pathways to the urinary bladder which may underlie the development of this instability. Our results suggest that among the factors involved in inflammation-induced bladder instability are significant changes in the expression of the neuropeptides substance P, calcitonin gene-related peptide and galanin at the primary afferent level, as well as of the enzyme neuronal nitric oxide synthase (nNOS) at the afferent and postganglionic efferent level. In the lumbar and sacral spinal cord nNOS-immunoreactivity was depleted from dorsal horn neurones in both cystitis and spinal cord injured rats and from preganglionic parasympathetic neurones after spinal cord injury. Distension of the bladder in chronically spinalized rats elicited c-Fos expression in a significantly greater number of neurones throughout the lumbar and sacral segments than in rats with an intact neuraxis. Thus, under pathological conditions rather complicated changes in the synthesis of neuropeptides and nNOS occur at the primary afferent, spinal cord and postganglionic efferent level that together control the activity of the urinary bladder. Further mechanisms like unmasking of silent synapses and axonal sprouting in the spinal cord might further contribute to an increase in activity in micturition reflex pathways. Local cooling of the dorsal spinal cord at the level L6/S1 with temperatures between 14 and 20 degrees C proved a simple technique to control the unstable bladder and restore continence in both inflammation-induced detrusor overactivity and detrusor hyperreflexia following spinal cord injury. The effects of cooling are probably the result of a blockade of synaptic transmission within the dorsal cord which eliminates neuronal overactivity. Thus, local spinal cord cooling could offer a new method to treat bladder instability and reflex incontinence.

Journal Article↗
PubMed1997

Myositis-induced functional reorganisation of the rat dorsal horn: effects of spinal superfusion with antagonists to neurokinin and glutamate receptors.

The study aimed at identifying some of the receptors for neurotransmitters/neuromodulators that are involved in the myositis-induced neuroplastic changes in spinal neurones. In anaesthetised rats, an experimental myositis was induced in the gastrocnemius-soleus muscle and the activity of single dorsal horn neurones recorded in the segment L3, just rostral to the main input region from that muscle. During the development of the myositis, the segment L3 was continuously superfused with antagonists to neurokinin receptors (GR 82.334, Spantide II), NMDA receptors (MK-801, AP 5) or AMPA/kainate receptors (CNQX). Each of the antagonists reduced the myositis-induced increase in excitability, but acted on different aspects of the hyperexcitability. GR 82.334 was most effective in preventing the expansion of the neurone population that responded to A-fibre input from the inflamed muscle, which was the main myositis effect in the present study. None of the antagonists influenced the background activity of the neurones. The results show that in the myositis-induced hyperexcitability of dorsal horn neurones all of the above receptors are involved. Excitability by peripheral input and background activity of the neurones are probably controlled by different mechanisms.

Animals↗