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Biomedical subjects

F Cervero

Publications and source records attributed to F Cervero.

At least 55 records · Page 3Linked to original sources

Tonic descending inhibition of spinal cord neurones driven by joint afferents in normal cats and in cats with an inflamed knee joint.

In ten cats, single unit electrical activity was recorded in the lumbosacral spinal cord from neurones driven by stimulation of afferent fibres from the ipsilateral knee joint. Tonic descending inhibition (TDI) on the responses of these cells was measured as increases in resting and evoked activity of the neurones following reversible spinalization of the animals with a cold block at upper lumbar level. Acute inflammation of the knee joint was induced in five of the cats by the injection of kaolin and carrageenan into the joint. TDI was observed in 25 of 33 neurones recorded in normal animals (76%) and in 36 of 40 (90%) neurones recorded in animals with acute knee joint inflammation. In both kinds of preparation TDI was more pronounced in neurones recorded in the deep dorsal horn and in the ventral horn than in those recorded in the superficial dorsal horn. There was a tendency in the whole sample for TDI to be greater in neurones with input from inflamed knees. We conclude that the spinal processing of afferent information from joints is under tonic descending influences and that the amount of TDI can be altered during acute arthritis.

Afferent Pathways↗

Mechanisms of acute visceral pain.

Acute visceral pain is dull, aching, ill-defined, badly localized and often referred to remote areas of the body. These properties indicate that the representation of internal organs within the CNS is very imprecise. There is evidence for the existence of specific visceral nociceptors in some viscera and for the existence of non-specific receptors in other internal organs. Some visceral receptors are 'silent' in normal viscera but become active following acute injury or inflammation of the internal organ that they innervate. The number of nociceptive afferent fibres in viscera is very small but these few nociceptive afferents can excite many second order neurones in the spinal cord which in turn generate extensive divergence within the CNS, sometimes involving supraspinal loops. Such a divergent input activates several systems--sensory, motor and autonomic--and thus triggers the general reactions that are characteristic of visceral nociception: a diffuse and referred pain, and prolonged autonomic and motor activity.

Acute Disease↗

Signalling of a step-like intensity change of noxious mechanical stimuli by dorsal horn neurones in the rat spinal cord.

1. Single-unit extracellular recordings were made from thirty-one dorsal horn neurones in the sacral spinal cord of barbiturate-anaesthetized rats. Each neurone was tested with four noxious mechanical pinches applied to its receptive field on the tail. Each pinch lasted 120 s, with a step-like change in intensity after 60 s. In two pinches the step increased the intensity, from 4 to 6 N or from 6 to 8 N, and in two the step decreased the intensity, from 8 to 6 N or from 6 to 4 N. 2. The ability of the neurones to signal these step changes in intensity was examined. Five neurones with an exclusively low-threshold afferent input (class 1) were tested, and found to fire only briefly at the start of the 120 s stimulus. Neurones with a high-threshold input (nociceptive neurones), either exclusively (class 3; n = 10) or in addition to a low-threshold input (class 2: n = 16), responded throughout the 120 s stimuli. 3. Nociceptive dorsal horn neurones have been divided into two groups of 'good' and 'poor' encoders on the basis of their response to the step changes in intensity. 4. 'Good' encoders (n = 13) were neurones signalling both a step increase and a step decrease in intensity, of which seven were class 2 and six class 3, five recorded in the superficial dorsal horn and eight in the deep dorsal horn. 5. 'Poor' encoders (n = 13) were neurones which failed to signal one or both of the step changes in intensity, of which nine were class 2 and four class 3, three recorded in the superficial dorsal horn and ten in the deep dorsal horn. 6. These results demonstrate that neurones with similar input properties and location are not necessarily a homogeneous group in terms of their processing of nociceptive stimuli. Moreover, they suggest that subgroups of both class 2 and class 3 and of superficial and deep dorsal horn neurones contribute to the different components of a nociceptive response. 7. We propose that the output and projection target of a particular dorsal horn neurone are more important than its afferent input in determining its role in nociceptive processing.

Animals↗

Changes in tonic descending inhibition of spinal neurons with articular input during the development of acute arthritis in the cat.

1. In 15 alpha-chloralose-anesthetized cats we studied the presence of tonic descending inhibition (TDI) of spinal neurons with input from the knee and its modulation during an acute inflammation of this joint. TDI of spinal neurons with articular input was assessed by applying reversible cold blocks to the lower thoracic cord. The amount of descending inhibition was estimated from the induction and/or increase of resting discharges and of the responses to mechanical stimuli to the knee and other structures during the transitory and reversible blocks. In each experiment one or a few neurons were investigated while the joint was in normal condition [altogether 15 nociceptive-specific (NS) and 6 wide-dynamic-range (WDR) neurons]. One of the neurons was then selected for long-term recordings during which an acute inflammation in the knee was induced by the intra-articular injection of kaolin and carrageenan. Before and during developing arthritis, cold blocks were applied to examine whether the amount of TDI would change during the inflammatory process. 2. The neurons with input from the normal knee were under TDI because application of the cold block induced or increased resting discharges and the responses to noxious compression of the knee and the adjacent thigh and lower leg. In 10 of 15 NS neurons, the response threshold was lowered into the innocuous range. In 9 of 17 cells tested, the excitatory receptive field expanded to the ipsilateral paw, and 4 neurons became inhibited by paw compression. Seven of 18 neurons tested revealed inhibitory receptive fields on the contralateral leg during cold block. The neurons were located in laminae IV-VII. 3. Fourteen neurons were continuously monitored during development of inflammation, and changes in the effectiveness of TDI were assessed by blocking the cord before and during the development of arthritis. In most neurons baseline resting activity in the intact state of the cord increased while the arthritis developed. This inflammation-evoked enhancement of resting discharges was more pronounced during periods of spinalization. Consequently, the differences between the resting discharges in the cold-blocked and the intact state were progressively enhanced in arthritis. 4. After induction of arthritis, the responses to compression of the knee joint increased in the intact state as well as during cold blocks. In 11 of 14 neurons, the differences between the responses in the spinal and intact state were progressively enlarged during the development of inflammation. A similar result was obtained for flexion of the injected knee.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The effects of electrical stimulation of A and C visceral afferent fibres on the excitability of viscerosomatic neurones in the thoracic spinal cord of the cat.

Single unit electrical activity has been recorded from viscerosomatic neurons in the lower thoracic spinal cord of decerebrate spinalized cats. The responses of the cells to electrical stimulation of afferent fibres in the splanchnic (SPLN) nerve and the effects of repetitive stimulation of somatic and visceral afferent C-fibres have been studied. Four groups of viscerosomatic neurones could be distinguished according to the type of visceral afferent input of the cells: (1) A-only cells (32.9%), driven only by stimulation of A delta afferent fibres in the SPLN nerve; (2) C-only cells (3%), driven only by stimulation of C afferent fibres in the SPLN nerve; (3) A + C cells (45.7%), driven by both A delta and C afferent fibres in the SPLN nerve; and (4) A + C? cells (18.6%), driven by A delta visceral afferents and showing signs of responsiveness to C-fibres though lacking a distinct response volley to visceral C-fibre activation. Two cells of the A + C group and located in lamina I of the dorsal horn responded to SPLN nerve stimulation in a manner consistent with the afferent fibre composition of the nerve, that is, showed evidence of strong monosynaptic links with SPLN afferent C-fibres and weaker responses to SPLN A delta afferents. Excitability changes of viscerosomatic neurones ('wind up', 'wind down' and changes in background activity) were also observed in the majority of neurones following electrical stimulation of somatic and of visceral afferent C-fibres.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Improvement of anal sensation with preservation of the anal transition zone after ileoanal anastomosis for ulcerative colitis.

One of the most important considerations in restorative proctocolectomy for ulcerative colitis is postoperative continence. Preservation of the anal transition zone has been associated with improved results after this procedure in the pediatric age group. This study was carried out to determine the effect of preservation of the amal transition zone in adult patients undergoing restorative proctocolectomy, comparing a group of patients with the anal transition zone preserved with a group of patients with the anal transition zone removed. Physiologic testing demonstrated improved sensation in those patients with a preserved anal transition zone. Functional results were not significantly improved, although there was a trend toward improved continence and discrimination in those with the anal transition zone preserved. Although the results are early and are not conclusive from the clinical standpoint, they are certainly encouraging and may justify continued use of this technique.

Adult↗

Tonic descending influences on receptive-field properties of nociceptive dorsal horn neurons in sacral spinal cord of rat.

1. Single-unit electrical activity has been recorded from 34 dorsal horn neurons in the sacral segments (S1-2) of the spinal cord in halothane-anesthetized rats. All of the neurons had cutaneous receptive fields (RFs) on the rat's tail. The neurons were classified according to their responses to both innocuous and noxious mechanical stimulation of their RFs. Twenty-five cells were driven by both innocuous and noxious skin stimulation (multireceptive or class 2), and 9 neurons were driven only by noxious skin stimulation (nocireceptive or class 3). 2. The RF size, mechanical threshold, and afferent input properties of these neurons were determined in the intact anesthetized and spinalized states. Reversible spinalization was achieved by cooling the cervical spinal cord to 4 degrees C. 3. The class 2 neurons had a mean RF size of 919.8 +/- 112.0 (SE) mm2 in the intact animal. Fourteen of the 25 class 2 cells had larger RFs in the spinal state (mean increase = 330.0 mm2, SE = 79.2) and so were under tonic descending inhibition. Five neurons, all with C-fiber input, had smaller RFs (mean decrease = 247.6 mm2, SE = 136.6) and higher mechanical thresholds in the spinal state and so were under tonic descending excitation. Six neurons were unaffected by spinalization. 4. Five class 3 neurons recorded in the superficial dorsal horn had small RFs in the intact animal (mean = 201.0 mm2, SE = 48.8) and showed little or no change in RF size on spinalization (mean increase = 33.4 mm2, SE = 16.7), but their mechanical thresholds did decrease, indicating weak tonic descending inhibition. In contrast, four class 3 neurons recorded in the deep dorsal horn had larger RFs in the intact animal (mean = 566.8 mm2, SE = 156.8), and were under strong tonic descending inhibition, because they had much larger RFs (mean increase = 461.0 mm2, SE = 68.3), lower mechanical thresholds, and stronger C-fiber afferent input in the spinal state. 5. We conclude that the majority of nociceptive dorsal horn neurons are subject to a net tonic descending control of their RF properties. The class 2 neurons in the deep dorsal horn appear to be a heterogeneous population, some cells being under tonic descending excitation and others under tonic descending inhibition. Class 3 cells can be separated into those located in the superficial dorsal horn, whose RF properties show very little change on spinalization, and those in the deep dorsal horn, whose RF properties change markedly on spinalization.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Modulation of a viscerosomatic reflex by electrical and chemical stimulation of hypothalamic structures in the rat.

Ventromedial forebrain structures were stimulated electrically with short (10-ms) trains of pulses to test for effects on a viscerosomatic reflex. Stimulation at many hypothalamic sites led to an attenuation or even a complete inhibition of reflex activity. The most sensitive sites, however (i.e. those requiring currents of 50 microA or less to inhibit the reflex), were located in the anterior hypothalamus/preoptic area (AH/POA) and rostrally in the diagonal band of Broca (DBB). At certain sites the effects of electrical stimulation were compared with those of microinjection of an excitatory amino acid (DL-homocysteic acid) which is known to excite neuronal cell bodies and not axons. The results of this part of the study indicated that activation of cell bodies located in the ventromedial AH/POA (from the level of the optic chiasma caudally to the level of DBB rostrally) mediate, at least in part, the inhibitory effects on visceral afferent processing. These data are discussed in relation to a possible role of AH/POA in the spinal processing of nociceptive information of visceral origin.

Animals↗

Differences in anal sensation in continent and incontinent patients with perineal descent.

Neuropathic damage secondary to pelvic floor descent is considered to be an important aetiological factor in idiopathic faecal incontinence. Perineal descent however does not necessarily result in a loss of motor function or incontinence. To elucidate the role of anal sensation in the continence mechanism we measured mucosal electrosensitivity and thermal sensitivity in normal controls and in both continent and incontinent patients with perineal descent. A catheter carrying two platinum electrodes was used to assess mucosal electrosensitivity and a water perfused thermode 1 cm long to measure thermal sensory thresholds. In addition, routine anal manometry was performed. The degree of perineal descent and anorectal angle was assessed radiographically. Anal sensation was largely preserved in continent patients with perineal descent (Controls vs continent perineal descent, Mucosal electrosensitivity (ma), lower anal canal: 4 (2-7) vs 5 (2.6-8) ns; middle anal canal 4 (2-7) vs 4.2 (2-15) ns; upper anal canal 6.5 (4-13) vs 8.3 (3.6-16) p less than 0.05, thermal sensitivity, median threshold (degrees C), lower anal canal 0.92 (0.5-2.5) vs 0.95 (0.3-3.6) ns; middle anal canal 0.83 (0.4-1.5) vs 0.75 (0.2-2) ns; upper anal canal 0.98 (0.6-2.4) vs 2.2 (0.5-4.8) p less than 0.05). There was a severe impairment of anal sensation in the incontinent patients with perineal descent despite a greater degree of perineal descent in the continent group. Loss of anal sensation is associated with the development of incontinence and is likely to be involved in the pathogenesis of the condition.

Adult↗

Visceral and somatic afferent origin of calcitonin gene-related peptide immunoreactivity in the lower thoracic spinal cord of the rat.

The origin of calcitonin gene-related peptide in the thoracic spinal cord of the rat was investigated by radioimmunoassay and immunohistochemistry. In transverse sections from normal animals there was a dense staining of calcitonin gene-related peptide-immunoreactivity in laminae I, II and V of the dorsal horn. In parasagittal sections this was found to consist of rostrocaudally orientated fibres in laminae I and II and longitudinal bundles of fibres interspersed with a plexus of immunoreactivity in lamina V. After sectioning the thoracic spinal nerves there was a significant reduction in immunoreactivity in the dorsal horn of the spinal cord which was seen as a marked reduction of staining in lamina II and in the bundles of fibres in lamina V. Section of the splanchnic nerve slightly reduced staining in lamina I and virtually abolished the plexuses of immunoreactivity in lamina V. However, measurement of calcitonin gene-related peptide in samples from coeliac-ganglionized rats revealed an increase in immunoreactivity in regions of the spinal cord containing lamina V. These results provide evidence of a visceral and somatic afferent origin of calcitonin gene-related peptide in the thoracic spinal cord of the rat.

Animals↗

Mechanically evoked responses of afferent fibres innervating the guinea-pig's ureter: an in vitro study.

1. Electrophysiological recordings from ureteric mechanosensitive afferent fibres were performed using an in vitro preparation of the guinea-pig ureter and associated nerves. Single-unit recordings were obtained from small ureteric nerves arising from the inferior mesenteric ganglion, the hypogastric nerve or the pelvic plexus. The fibre composition of these ureteric nerves was also examined by electron microscopy. 2. In two ureteric nerve bundles, which were taken as representative of the maximal and minimal size of nerves used in the electrophysiological recordings, the number of nerve fibres was found to be 417 and 48, respectively. In the bigger nerve 12% of the fibres were small myelinated and the rest unmyelinated. The smaller nerve consisted of unmyelinated fibres only. 3. Electrophysiological recordings were made from sixty-seven mechanosensitive afferent fibres. The conduction velocities (CV) of forty-two of them were determined and all were found to be in the C fibre range (mean CV, 0.4 m/s). Of 119 additional fibres which were not further characterized 112 were C fibres (mean CV, 0.51 m/s) and seven were A delta fibres (mean CV, 3.78 m/s). 4. Mechanosensitive units were classified into two groups according to their ability to respond to contractions of the ureter: (i) U-1 units (9% of all mechanosensitive units) responded to contractions of the ureter and did not show on-going activity or after-discharges to mechanical stimulation. They had low thresholds to intraluminal distension (mean, 8 mmHg) and responded with a short latency to pressure stimuli. (ii) U-2 units (91% of all mechanosensitive units) did not respond to contractions of the ureter, had spontaneous activity between 0 and 2.4 Hz and exhibited after-discharges to mechanical stimuli lasting up to several minutes. They responded after a long latency (greater than 3 s) to distensions in the range of 5-30 mmHg. 5. The level of spontaneous activity and the pressure thresholds of the U-2 units were found to be different depending on whether or not the ureter was perfused intraluminally. Thus U-2 units recorded with intraluminal perfusion had a lower rate of on-going activity and higher threshold to intraluminal distension than U-2 units recorded without intraluminal perfusion. 6. Movement of an intraluminal glass bead under the receptive field of the units evoked strong responses in nine of eleven U-2 units tested as soon as their receptive fields were reached. 7. Our results demonstrate the existence of two classes of mechanosensitive afferent fibres in the guinea-pig ureter.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

A comparative study of the changes in receptive-field properties of multireceptive and nocireceptive rat dorsal horn neurons following noxious mechanical stimulation.

1. Single-unit electrical activity has been recorded from 42 dorsal horn neurons in the sacral segments of the rat's spinal cord. The sample consisted of 20 multireceptive (class 2) cells with both A- and C-fiber inputs and 22 nocireceptive (class 3) cells. All neurons had cutaneous receptive fields (RFs) on the tail. 2. The RF sizes of the cells and their response thresholds to mechanical stimulation of the skin were determined before and after each of a series of 2-min noxious mechanical stimuli. Up to five such stimuli were delivered at intervals ranging from 10 to 60 min. In most cases, only one cell per animal was tested. 3. The majority of neurons were tested in barbiturate-anesthetized animals. However, to test whether or not this anesthetic influenced the results obtained, experiments were also performed in halothane-anesthetized and decerebrate-spinal preparations. The results from these experiments are considered separately. 4. All of the neurons responded vigorously to the first noxious pinch stimulus and all but one to the rest of the stimuli in the series. The responses of the neurons varied from stimulus to stimulus, but there were no detectable trends in the two groups of cells. 5. The RFs of the class 2 cells showed large increases (624.3 +/- 175.8 mm2, mean +/- SE) after the application of the pinch stimuli. The RFs of the class 3 neurons, which were initially smaller than those of the class 2 cells, either did not increase in size or showed very small increases after the pinch stimuli (38.3 +/- 11.95 mm2, mean +/- SE). 6. Some cells in both groups (6/10 class 2 cells and 7/16 class 3 cells) showed a decrease in mechanical threshold as a result of the noxious mechanical stimulus, but none of the class 3 cells' thresholds dropped below 20 mN into the low-threshold range. 7. The results obtained in the halothane-anesthetized and decerebrate-spinal animals were very similar to those seen in the barbiturate-anesthetized experiments, with the exception that in the decerebrate-spinal animals, the RFs of the class 2 cells were initially larger and showed only small increases.(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesia↗

Anorectal sampling: a comparison of normal and incontinent patients.

It has been suggested that sampling of rectal contents by the anal canal may play a role in the continence mechanism. To investigate this concept we studied 18 patients with faecal incontinence and 18 age and sex matched controls. A microtransducer catheter was positioned so that pressures were recorded from the rectum, the junction of the upper and middle thirds of the anal canal and the lower anal canal. Recordings were taken at rest and while distending the rectum with air in a balloon, and then with air injected freely into the rectum. Sampling (equalization of the rectal and upper anal canal pressures) was seen to occur spontaneously in 16 of the controls and only 6 of the incontinent group (P less than 0.02) and induced sampling occurred at a higher rectal volume in the incontinent group than in controls for freely injected air (P less than 0.002). Defective anorectal sampling may be an important contributory factor in the pathogenesis of anorectal incontinence.

Adult↗

Sensory discrimination and dynamic activity in the anorectum: evidence using a new ambulatory technique.

The anal canal in health is extremely sensitive to thermal stimuli, If temperature sensation plays a part in sensory discrimination two conditions must be fulfilled: there must be a temperature gradient along the anorectum and rectal contents must be able to come into contact with the sensitive anal mucosa. In a study of 53 normal subjects we demonstrated this temperature gradient with a median temperature difference between the rectum and lower, mid and upper anal canal of 0.4, 0.2 and 0.1 degrees C respectively. The second condition was examined in 15 normal ambulatory subjects by measuring mid-anal sphincter (SP) and rectal pressures (RP) with a microtransducer catheter. The signals were digitalized and recorded in a portable electronic memory for later computer display, and analysis. Marked spontaneous sphincter relaxation resulting in equalization of RP and SP occurred 7 times per hour (1-4). The conscious sensation of the presence of flatus was associated with an SP reduction of 30 mmHg (20-50 mmHg) and an RP increase of 7 mmHg (0-15 mmHg), such that RP greater than or equal to SP in 80 per cent of 144 recorded events. Using this new technique we have demonstrated the highly dynamic nature of the anal sphincter. Several times an hour the sphincter relaxes with subsequent equalization of rectal and anal pressures, allowing entry of rectal contents into the anal canal so that its presence and nature can be determined.

Adult↗

Afferent innervation of the guinea-pig's ureter.

The electrical activity of 41 mechanosensitive afferent units was recored using an in vitro preparation of the guinea-pig's ureter. The conduction velocities of these fibres were found to be in the C-fibre range. Only 4 of them responded to contractions of the ureter. The activation threshold of the units to intraluminal (i.l.) pressure varied between 3 and 50 mm Hg. It is concluded that some of these afferent fibres might be involved in the signalling of nociceptive events.

Animals↗

Anal sensation and the continence mechanism.

Thermal sensation is thought to be important in sensory discrimination between different substances. The aim of this study was to determine the thermal sensitivity in the anal canal in continent patients with hemorrhoids (N = 20), a group that has been reported to have a sensory deficit, and to compare the results with control subjects (N = 40) and patients with idiopathic fecal incontinence (IFI) (N = 22). Anal manometry was performed and sensation to mucosal electrostimulation and temperature change in the lower, middle, and upper zones of the anal canal assessed. Thermal sensation was impaired in the hemorrhoid group as compared with controls, but not to the same degree as in IFI (e.g., median thermal sensitivity in mid anal canal, control 0.9 degrees C, hemorrhoid 1.2 degrees C, IFI 2.0 degrees C, P less than .05 and less than .001, respectively). The correlation between the two tests of sensation was 0.54 (P less than .001) and the reproducibility of thermal sensory thresholds was 0.82 (P less than .001). In conclusion, patients with hemorrhoids have a mild anal sensory deficit, but continence in this group is likely to be augmented by other factors.

Adult↗

Neurophysiology of gastrointestinal pain.

The only non-general sensation that can be evoked from the gastrointestinal (GI) tract is that of pain ranging from mild discomfort to intense pain. However, in certain regions of the gut, such as the rectum and gastro-oesophagus, the feeling of pain can be preceded by non-painful sensations of distension at lower stimulus intensities. GI pain is often dull, aching, ill-defined and badly localized. In some cases, GI pain is projected to areas of the body away from the originating viscus ('referred' pain). These properties indicate that the representation of internal organs within the central nervous system is very imprecise. Behavioural, neurophysiological and clinical evidence shows that most forms of GI pain are mediated by activity in visceral afferent fibres running in sympathetic nerves and that the afferent innervation of the gut mediated by parasympathetic nerves is not primarily concerned with the signalling and transmission of GI pain. As for the encoding mechanism of the peripheral sensory receptor in the gut, there is evidence for the existence of specific visceral nociceptors in some locations (e.g. the biliary system) and for the existence of non-specific 'intensity' type receptors in other locations (e.g. the colon). In any case, the actual number of nociceptive afferent fibres in the gut is very small and this explains why large areas of the GI tract appear to be insensitive or require considerable stimulation before giving rise to painful sensations. The few nociceptive afferents contained in sympathetic nerves can excite many second order neurones in the spinal cord which in turn generate extensive divergence within the spinal cord and brain stem, sometimes involving long supraspinal loops. Such a divergent input can activate many different systems, motor and autonomic as well as sensory, and thus trigger the general reactions that are characteristic of visceral nociception: a diffuse and ill-localized pain sometimes referred to somatic areas, and autonomic and somatic reflexes that result in prolonged motor activity.

Afferent Pathways↗