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S Mense

Publications and source records attributed to S Mense.

At least 37 records · Page 2Linked to original sources
PubMed2000

Changes in the number of nitric oxide-synthesizing neurones on both sides of a chronic transection of the rat spinal cord.

Pain after chronic transection of the spinal cord is hypothesized to develop because of a hyperactivity in nociceptive neurones rostral to the lesion. One of the key substances in central nervous nociceptive processing is nitric oxide (NO). It has been demonstrated to tonically inhibit the background activity of dorsal horn neurones. Here, we show that in rats with chronic transection of the spinal cord there is a reduction of NO-synthesizing neurones on both sides of the lesion. This reduction is likely to be associated with a local lack of NO which could lead to an increased background activity of nociceptive dorsal horn neurones. The increased background activity of nociceptive neurones just rostral to the lesion might cause spontaneous pain that is perceived in segments close to the level of the lesion.

Animals↗
PubMed2000

Contribution of TTX-resistant C-fibres and Adelta-fibres to nociceptive flexor-reflex and non-flexor-reflex pathways in cats.

The contribution of Adelta-fibres and C-fibres activated by noxious heat stimulation of the central pad of the foot to nociceptive spinal flexor reflex pathways (FRA-type) and to nociceptive excitatory reflex pathways to foot extensors (non-FRA type) was investigated in high spinal cats. A-fibres were completely blocked by tetrodotoxin (TTX), leaving C-fibre conduction intact. Thus, effects persisting after TTX were attributed to nociceptive C-fibres while the contribution of nociceptive Adelta-fibres was defined by the difference between those effects and the control effects before TTX. The initial action of noxious stimulation on both types of reflex action was mediated predominantly by Adelta-fibres, while the later action was mainly mediated by C-fibres. In two (out of seven) experiments Adelta-fibres exerted a significant inhibitory influence on the C-fibre action in FRA pathways, but such an inhibitory interaction between the two fibre groups was absent in the non-FRA reflex pathways. The technique of TTX application at the peripheral nerve proved to be a reliable method for a long-lasting selective investigation of C-fibre effects. The results revealed that both Adelta- and C-fibres contributed to nociceptive FRA and non-FRA reflex pathways.

Animals↗
PubMed2000

Neurobiological concepts of fibromyalgia--the possible role of descending spinal tracts.

In the spinal cord, long descending pathways are known to exist which modulate pain sensations by either inhibiting or facilitating the discharges of spinal nociceptive neurones. In this article, the hypothesis is discussed that the pain of fibromyalgia may be due to a dysfunction of these pain-modulating pathways. Theoretically, two kinds of disturbance could lead to pain, namely reduced activity in the pain-inhibiting (antinociceptive) system or increased activity in the pain-facilitating (pronociceptive) pathways. Data from animal experiments show that interruption of the dorsal descending systems leads to hyperactivity of spinal nociceptive neurones, namely increase in background activity, lowering in stimulation threshold, and increase in response magnitude to noxious stimuli. The responses of the neurones to input from nociceptors in deep tissues were more strongly inhibited by the descending pathways than were responses to input from cutaneous nociceptors. Collectively, the findings indicate that the dorsal descending systems are tonicly active and have a particularly strong inhibitory action on neurones that mediate pain from deep tissues. If these systems operate in a similar way also in patients, an impairment of their function is likely to lead to 1. spontaneous deep pain (because of an increased background activity in nociceptive neurones supplying deep tissues), 2. tenderness of deep tissues (because of a lowered mechanical threshold of the same neurones), and 3. hyperalgesia of deep tissues (because of increased neuronal responses to noxious stimuli). These changes will affect large areas of the body because the descending inhibitory systems have widespread terminations in the spinal cord. Thus, a dysfunction of the descending inhibitory pathways could mimick to a large extent the pain of fibromyalgia.

Animals↗
PubMed1999

[Neurobiological basis of muscle pain].

MECHANISMS IN THE LESIONED MUSCLE: The peripheral mechanism underlying the tenderness and pain during movement of a damaged muscle is the sensitization of muscle nociceptors. Ongoing activity of nociceptors causes spontaneous pain in addition to tenderness. Muscle pain (particularly that originating in myofascial trigger points) is often mislocalized because it is referred to other deep somatic tissues. The development of trigger points is a purely peripheral event, whereas the referral of muscle pain is based on central nervous mechanisms. MECHANISMS AT THE SPINAL LEVEL: The input from muscle nociceptors induces neuroplastic changes in the spinal cord and higher centres of the central nervous system. These changes are associated with an overexcitability of neurones (central sensitization) and contribute to hyperalgesia of patients. Resting activity of spinal neurones (and hence spontaneous pain) is strongly dependent on nitric oxide (NO). A muscle lesion is likely to lead to an inhibition of the homonymous muscle, it can, however, elicit spasm in another muscle. SUPRASPINAL MECHANISMS: Spinal neurones that mediate muscle pain are subjected to a strong descending inhibitory influence. The inhibitory tracts originate in the mesencephalon and medulla oblongata. A dysfunction of this inhibitory system might be involved in the pathogenesis of fibromyalgia.

English Abstract↗
PubMed1999

Increased spinal expression of c-Fos following stimulation of the lower urinary tract in chronic spinal cord-injured rats.

c-Fos expression was studied in the lumbar and sacral spinal cord regions involved in processing afferent input from the lower urinary tract and a comparison was made between spinal cord-injured (SCI) animals and control animals with intact neuraxes. Afferent pathways from the lower urinary tract were activated either by insertion of a catheter through the urethra into the urinary bladder or by catheterisation plus induction of reflex micturition contractions by intravesical saline infusion. Placement of a catheter alone elicited Fos expression in a similar number of neurones in SCI and control rats mainly in the medial dorsal horn (MDH) and dorsal commissure (DCM) in the segments L1-2 and L5-S1 with a maximum in L5. Additional saline infusion induced low-frequency, high-amplitude, rhythmic bladder contractions of long duration in the rats with intact spinal cords, whereas in SCI rats, bladder distension elicited reflex contractions at a higher frequency, smaller amplitude and shorter duration. However, the basal and mean bladder pressure, as well as the total contraction time relative to the whole recording time, was not significantly different. Distension-induced bladder contractions markedly increased Fos expression primarily in the spinal segments L5-S1 in the control rats, where the majority of bladder and urethral afferent fibres terminates. Fos-positive cells were located in the MDH, lateral dorsal horn (LDH), DCM and the lateral aspect of laminae V-VII. Compared to controls, Fos expression after spinal cord injury (SCI) occurred in a significantly greater number of neurones throughout the segments L3-S1 following induction of bladder reflexes. The greatest proportional increase in the number of Fos-positive cells occurred in L3-5 which normally receive only little afferent input from the urinary bladder. Cell numbers predominantly increased in the LDH and lateral lamina V-VII. The data are consistent with the concept of a neuroplastic reorganisation of spinal pathways after SCI. Unmasking of silent synapses or formation of new connections by afferent axonal sprouting caudal to the lesion, as evident from the increased numbers of cells expressing Fos after bladder distension, could be factors underlying the emergence of reflexogenic micturition in chronic SCI rats.

Afferent Pathways↗
PubMed1999

The controversy about spinal neuronal nitric oxide synthase: under which conditions is it up- or downregulated?

In recent years, the regulation of the synthesis of nitric oxide (NO) in the central nervous system has attracted much interest because it has been shown that NO is involved in a wide variety of functions such as neuroprotection, neurotoxicity, neurotransmission, and neuroplasticity under physiological and pathophysiological conditions. However, the use of different detection techniques for neuronal nitric oxide synthase (nNOS), different animal species, and different experimental lesions has led to contradictory results concerning the direction of changes in spinal nNOS expression. This paper summarizes the available data on the expression on nNOS in the spinal cord under physiological and pathological conditions and tries to extract some of the basic mechanisms that underlie neuronal up- or downregulation of this enzyme. Wherever possible, results obtained with the NADPH-dependent diaphorase reaction are also included for reasons of comparison. The main conclusion is that changes in spinal nNOS expression critically depend on the type of afferent fibres activated by a specific lesion as well as the intensity and duration of input to the spinal cord. This input may be further modified by supraspinal influences. Thus the exact composition of these factors, which is undoubtfully highly variable between different experimental models, appears to determine whether the spinal NO system responds with an up- or downregulation of nNOS expression or in a bidirectional way. With regard to the diaphorase reaction it is becoming increasingly clear that under pathological conditions data obtained with this reaction differ markedly from those obtained with immunohistochemical visualization of nNOS.

Animals↗
PubMed1999

Control of the unstable urinary bladder by graded thermoelectric cooling of the spinal cord.

OBJECTIVE: To evaluate local lumbosacral spinal-cord cooling (a novel technique for neuromodulating urinary bladder reflexes) for its feasibility in possible clinical use, by determining the efficacy and the optimum temperature for suppressing reflex urinary incontinence in two rat models of neurogenic urinary bladder instability. MATERIALS AND METHODS: Overactivity of the detrusor muscle was induced by inflammation of the urinary bladder in a group of rats. A second group of rats was examined 6 weeks after complete midthoracic spinal cord transection, when all animals had developed neurogenic bladder hyper-reflexia. The intravesical pressure, urethral pressure and electromyographic (EMG) activity of the external urethral sphincter (EUS) were recorded simultaneously during repetitive local cooling and re-warming of the dorsal L6/S1 spinal cord segments, using a thermoelectric cooling device. RESULTS: Spinal cord cooling at L6/S1 had no influence on the recorded values at >26 degrees C, but markedly suppressed detrusor contraction frequency at 21- 25 degrees C. Cooling to <20 degrees C completely and reversibly eliminated inflammation-induced bladder contractions in rats with an intact neural axis and significantly reduced the contraction amplitudes (mean reduction 61%) and duration of contractions in spinally transected rats. Cooling simultaneously increased tonic EUS EMG activity and urethral perfusion pressure in both experimental groups, indicating closure of the urethral outlet. Cooling of adjacent spinal cord segments had no influence on bladder and urethral functions. CONCLUSION: Cooling the dorsal spinal cord at the origin of the parasympathetic innervation of the bladder can be used to reversibly suppress bladder instability with simultaneous closure of the urethral outlet. Therefore, local spinal cord cooling, e.g. as an implantable thermoelectric device, may offer a suitable method to treat detrusor overactivity and restore continence.

Animals↗
PubMed1998

Relationship between neuronal activity and substance P-immunoreactivity in the rat spinal cord during acute and persistent myositis.

The spinal level of substance P (SP) is assumed to be an important determinant of neuronal activity under pathophysiological conditions. In rat dorsal horn neurones, impulse activity was studied during a carrageenan-induced acute (2-8 h) and a Freund's adjuvant-induced persistent (12 days) myositis and compared with the spinal substance P-immunoreactivity (SP-IR) of the same animals. Myositis-induced changes in responsiveness of the neurones reached a maximum within 2-8 h, whereas background activity of the neurones was highest after 12 days of myositis. The area of SP-IR in the superficial dorsal horn decreased during acute and persistent myositis and the integrated density of the staining was largely unchanged. The difference in time-course between neuronal activity and SP-IR suggest that during persistent myositis factors other than SP gain more influence on the behaviour of the neurones.

Acute Disease↗
PubMed1998

Inflammation-induced increase in the density of neuropeptide-immunoreactive nerve endings in rat skeletal muscle.

The density of substance P (SP)-, calcitonin gene-related peptide (CGRP)- and vasoactive intestinal polypeptide (VIP)-immunoreactive (ir) nerve endings was quantitatively evaluated in intact and inflamed gastrocnemius-soleus muscle of the rat. In persistently inflamed muscle (12 days after a single injection of Freund's adjuvant into the muscle), the density of SP-ir fibres was significantly increased. CGRP- and VIP-ir fibres displayed an insignificant increase in density. The density of fibres ir for nerve growth factor (NGF) and for growth-associated protein 43 (GAP-43/B-50), a marker for axonal sprouting, regeneration and synaptic reorganisation, increased significantly in persistently inflamed muscle. The data are consistent with the established contribution of NGF on the expression of SP and GAP-43 in afferent neurones under the influence of a persistent inflammation.

Animals↗
PubMed1998

Descending antinociception and fibromyalgia.

The hypothesis is discussed that a dysfunction of the descending antinociceptive system may underly the pain of fibromyalgia. Data from animal experimentation show that an interruption of the system by spinal cord cooling leads to (1) increase in ongoing activity, (2) lowering in stimulation threshold, and (3) increase in response magnitude in nociceptive dorsal horn neurons. The influence of the descending system was stronger on the responses to input from deep nociceptors than to input from cutaneous nociceptors. If similar changes occur also in patients, an impairment of the tonicly active descending system should be followed by (1) spontaneous pain (ongoing activity), (2) tenderness (lowering in mechanical threshold), and (3) hyperalgesia (increased responses to noxious stimuli). These changes should affect mainly deep pain, because the antinociceptive system influences predominantly input from deep nociceptors.

Animals↗
PubMed1998

Understanding and measurement of muscle tone as related to clinical muscle pain.

Measurable sources of muscle tension include viscoelastic tone, physiological contracture (neither of which involve motor unit action potentials), voluntary contraction, and muscle spasm (which we define as involuntary muscle contraction). The latter two depend on motor unit action potentials to generate the tension. Total muscle tension is most accurately measured as stiffness. Thixotropy of muscle is an ubiquitous and functionally important phenomenon that is not commonly recognized. A clinical pain condition associated with increased muscle tension is tension-type headache, which is largely muscular in origin; it is often caused by myofascial trigger points, but not by a pain-spasm-pain cycle, which is a physiologically and clinically untenable concept. Clinical conditions associated with painful muscle spasm include spasmodic torticollis, trismus, unnecessary muscle tension, nocturnal leg cramps, and stiff-man syndrome.

Biomechanical Phenomena↗
PubMed1998

Abolition of cystitis-induced bladder instability by local spinal cord cooling.

PURPOSE: The efficacy of lumbosacral spinal cord cooling for the suppression of reflex urinary incontinence was evaluated in a rat model of cystitis-induced bladder instability. MATERIALS AND METHODS: In female Sprague-Dawley rats, overactivity of the detrusor muscle was induced by inflammation of the urinary bladder. Isovolumetric intravesical pressure, urethral perfusion pressure and electromyographic (EMG) activity of the external urethral sphincter (EUS) were recorded simultaneously during repetitive local cooling (-2C or +15C) and rewarming (to 37C) of the dorsal L6/S1 spinal cord segments. RESULTS: Mustard oil-induced inflammation led to a marked instability of the urinary bladder without affecting urethral outlet functions. Local cooling of the dorsal lumbosacral spinal cord with temperatures of -2C as well as +15C completely abolished bladder voiding contractions in rats with an inflamed bladder as well as in non-inflamed control animals. Cooling had little effect on the EMG activity of the EUS and increased the urethral perfusion pressure. The suppression of detrusor reflex contractions was reversed within 1-7 min. after rewarming of the spinal cord. CONCLUSIONS: Cooling of the dorsal spinal cord at the origin of the parasympathetic innervation of the bladder can be used for a reversible suppression of bladder instability without affecting the urethral outlet. Thus, local spinal cord cooling may offer a suitable method to restore continence in cases of reflex incontinence.

Animals↗
PubMed1997

Expression of neuropeptides and nitric oxide synthase in neurones innervating the inflamed rat urinary bladder.

Micturition reflexes become hyperexcitable with the development of a cystitis. In the present study the question is addressed, whether alterations in the expression of neuropeptides and nitric oxide synthase (NOS) in the neuronal pathways to the bladder may be involved in the hyperexcitability. Primary sensory neurones in the dorsal root ganglia (DRG) L1, L2, L6 and S1 as well as postganglionic efferent neurones in the major pelvic ganglia (MPG) that innervate the rat urinary bladder were labeled with retrogradely transported Fast Blue (FB). Immunocytochemical techniques were used to determine alterations in the expression of calcitonin gene-related peptide (CGRP), substance P (SP), galanin (GAL) and NOS in these neurones following mustard oil-induced inflammation of the urinary bladder. Instillation of 2.5% mustard oil into the bladder led to a massive leukocyte infiltration of the vesical tissues, partial damage of the mucosal layer and a marked hyperreflexia of the detrusor muscle. 48 h after induction of the cystitis the proportion of FB-labeled bladder afferent neurones that expressed CGRP and SP were significantly increased in both the rostral lumbar DRGs (L1, L2) and the lumbosacral DRGs (L6, S1) (CGRP, +15-38%; SP, +47-158%) as compared to control animals. However, there was a differential effect of the inflammation on the expression of GAL and NOS in bladder afferents at the two segmental levels examined. Significant alterations in the number of FB-labeled afferents exhibiting GAL immunoreactivity were mainly restricted to the lumbosacral DRGs L6 (+169%) and S1 (+60%). On the contrary, the proportion of NOS-immunoreactive bladder afferents significantly increased only in the rostral lumbar DRGs L1 (+144%) and L2 (+193%), while the level of NOS-expression was unaffected at the lumbosacral levels. Inflammation furthermore induced a significant increase (+275%) in the number of FB-labeled neurones in the MPGs that exhibited NOS immunoreactivity. These results indicate that an upregulation of CGRP-, SP-, GAL- and NOS-synthesis in sensory and efferent neurones is involved in the response to an acute cystitis. Because of the differences in the segmental pattern and degree of upregulation of these substances in bladder afferents that project to the rostral lumbar and lumbosacral spinal cord a different regulation of the sympathetic and parasympathetic efferent outflow to the urinary bladder is suggested. The involvement of CGRP, SP, GAL and NOS in the modulation of both excitatory and inhibitory mechanisms that control the cystitis-induced detrusor hyperreflexia is discussed.

Animals↗
PubMed1997

Frequency-dependent expression of diaphorase staining and nNOS-immunoreactivity in rat dorsal horn neurones following C-fibre stimulation.

Recent evidence demonstrated that lesion-induced central nervous system changes are at least partly mediated by the action of the gaseous transmitter nitric oxide (NO). We investigated the hypothesis that the frequency of peripheral C-fibre stimulation determines the number of neurones in the dorsal horn that can be visualised immunohistochemically with antibodies to NO synthase (NOS) or using the NADPH-dependent diaphorase (NDP) reaction. C-fibre stimulation of the sciatic nerve at a frequency of 0.01 Hz was followed by a significant increase in NDP-cell number in the spinal segment L3, whereas 0.1 and 1 Hz stimulation resulted in a significant decrease. Neuronal NOS (nNOS)-immunoreactivity was significantly influenced only by 1 Hz stimulation and only on the ipsilateral side in L3. Here, the number of nNOS-immunoreactive (ir) neurones decreased significantly in the superficial dorsal horn. The results show that the system of NDP-neurones is capable of displaying a bidirectional response depending on the frequency of C-fibre input.

Animals↗
PubMed1997

Experiments on the nature of the signal that induces spinal neuroplastic changes following a peripheral lesion.

This study aimed at identifying the signal(s) that elicit myositis-induced neuroplastic changes in background activity and responsiveness of spinal neurones. It is based on previous data suggesting that in dorsal horn neurones, responsiveness to peripheral input on one hand and background activity on the other are probably controlled by different mechanisms. In anaesthetized rats, myositis was induced in the gastrocnemius-soleus muscle and the activity of single dorsal horn neurones was recorded in segment L3. Impulse traffic and axoplasmatic transport in dorsal roots L4 and L5 were selectively blocked by lignocaine or vinblastine for various time periods relative to the induction of the myositis. The results show that the main triggering signal for the myositis-induced changes in both responsiveness and background activity is the altered impulse activity in primary afferent fibres. In contrast, 'no axonally transported chemical signal controlling the discharge behaviour of dorsal horn neurones was found. However, the time course of the electrical signals that cause the myositis-induced changes in background activity and responsiveness is different. For changes in responsiveness, a rather narrow time window of 2 h directly after induction of the myositis existed, during which the impulses from the inflamed muscle must reach the spinal cord. Accordingly, to prevent the increase in responsiveness, the electrical input had to be blocked during the first 2 h; a block of the same duration at another time had no effect. The change in background activity seems to be due to a continuous input from the inflamed muscle which adds up over the hours. Therefore, with regard to background activity, blocking the electrical signals is effective at any time, but only a block of long duration has a significant effect.

Journal Article↗