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Biomedical subjects

F Cervero

Publications and source records attributed to F Cervero.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effects of artificial calculosis on rat ureter motility: peripheral contribution to the pain of ureteric colic.

The contribution of changes in ureter motility produced by a stone to the pain of ureteric calculosis is unclear. In this study we measured ureter motility as changes in intraureter pressure in anesthetized rats 1, 4, and 8 d ys after implantation of an artificial calculus (n = 33) and compared it with motility in normal (n = 8) and ligated (n = 4) ureters. Partial obstruction of the ureter by the stone produced a 478% increase in the amplitude of contractions, a 70% decrease in the rate of contractions, and a 66% decrease in the baseline pressure. The pressures reached during contractions were equivalent to those evoking nociceptive reactions in animals and humans. These changes persisted in rats that had spontaneously eliminated the stone. Complete obstruction of the ureter by the stone or by ligation abolished contractions. We conclude that the increased motility caused by a stone likely contributes to the development and maintenance of visceral pain and referred hyperalgesia in ureteric colic and to the persistence of referred hyperalgesia after elimination of the stone.

Animals↗
PubMed1996

Supraspinal influences on the facilitation of rat nociceptive reflexes induced by carrageenan monoarthritis.

During hyperalgesia there is an enhancement of wind-up and the appearance of a novel wind-up of the A-fibre-mediated responses. We have examined if these phenomena are influenced by supraspinal mechanisms by analysing single motor unit activity in control and arthritic rats, either intact or acutely spinalised. Enhancement of the C-fibre wind-up and the novel A-fibre wind-up were only observed in the intact arthritic animals. We conclude that C-fibre wind-up is a spinal phenomenon, whereas the enhancement of the C-fibre wind-up and the novel A-fibre wind-up during arthritis depend also on supraspinal influences.

Analysis of Variance↗
PubMed1996

Changes in nociceptive reflex facilitation during carrageenan-induced arthritis.

Facilitation of neuronal responses induced by repetitive electrical stimulation of C-fibres (wind-up) is thought to be a substrate of hyperalgesia. There is little information on how these responses are in turn modified during hyperalgesia, and the extent to which hyperalgesic states also induce a facilitation of the neuronal responses mediated by A-fibres. The current study was undertaken in order to evaluate the effects of peripheral inflammation and stimulus presentation on the facilitation of nociceptive reflexes. Flexor reflexes, recorded as single motor units, were evoked in rats by cycles of low and high frequency electrical stimulation with pulse durations of 0.2, 0.5 and 2 ms. Responses were studied in control and inflammatory conditions, using the carrageenan-induced mono-arthritis model. The results show that the facilitation of late (C-fibre mediated) responses was proportional to the pulse duration of stimulation, as well as to the stimulation frequency. Facilitation was always higher when animals were subjected to inflammation. In inflammatory conditions, facilitation of reflexes was observed not only for late (C-fibre mediated) but also for early (A-fibre mediated) reflex responses. However, the facilitation of these early responses was not proportional to the intensity of stimulation. Thus, in arthritic animals, late (C-fibre mediated) flexion reflexes elicited from the skin, are facilitated and early (A-fibre mediated) reflexes are not only facilitated but, in addition, show a novel wind-up phenomenon.

Action Potentials↗
PubMed1996

Mechanisms of allodynia: interactions between sensitive mechanoreceptors and nociceptors.

We examined whether stimulation of sensitive mechanoreceptors from an area of allodynia evokes nociceptor activity expressed as axon reflexes. Experiments were conducted on human volunteers. Cutaneous blood flow was measured with a laser Doppler flowmeter. Allodynia was induced with mustard oil (25-100%) or by intradermal injections of capsaicin (25-50 micrograms) in the skin of the forearm or the hand. Tactile stimulation of normal skin or outside zones of allodynia did not evoke axon reflexes. The same stimulation in areas of allodynia evoked pain as well as axon reflexes. Cooling the area of primary hyperalgesia or blocking the A fibres in the nerve that innervated the allodynia area abolished the allodynia and the axon reflex. These results demonstrate central interactions between sensitive mechanoreceptors and nociceptors concomitant with the development of allodynia.

Adult↗
PubMed1996

Effects of metamizol on nociceptive responses to stimulation of the ureter and on ureter motility in anaesthetised rats.

In this study, we have examined the effects of metamizol (dipyrone), a non-opioid analgesic which is effective in relieving renal colic pain, on nociceptive responses evoked by stimulation of the ureter, on pyeloureteral motility and on intraureter pressure after ureter obstruction in anaesthetised rats. Metamizol (5- 50 mg/kg i.v.) dose-dependently inhibited reflex pressor responses evoked by distensions of the ureter to pressures of 30, 55 and 75 mmHg for 30 s (ID50 = 8 +/- 1 mg/kg). Metamizol also dose-dependently reduced intraureter pressure during total ureter occlusion (25 mg/kg produced a reduction of 25% in 10 min). However, metamizol at doses up to 50 mg/kg had no effect on pyleoureteric motility (contraction amplitude, rate or intraureter pressure) under normal pressure conditions. We conclude that metamizol has a direct antinociceptive action on pain of ureteric origin, and spasmolytic effects after ureter obstruction (but not under normal conditions) which may also contribute to pain relief.

Analgesics, Non-Narcotic↗
PubMed1996

Spinal dorsal horn neurons responding to noxious distension of the ureter in anesthetized rats.

1. Stimulation of the ureter in humans evokes only painful sensations. A large proportion of ureteric afferents show high activation thresholds to ureter pressure increases and encode stimuli within the noxious range. However, little is known about how these properties are reflected in the central processing of ureteric information. In this study, dorsal horn neurons recorded in the left side of the T12-L1 spinal cord of anesthetized rats have been tested for responses to innocuous and noxious pressure stimuli applied to the ipsilateral ureter. 2. Single-unit recordings were made from 76 neurons with somatic receptive fields on the left flank, of which 57 were fully characterized and tested by raising the ureter pressure to 80 mmHg for 30 s. Of these 57 neurons, 24 (42%) were influenced by the ureter stimulus, as follows: 18 were excited, 2 were inhibited, and 4 showed changes in background activity and/or in somatic receptive field area, without a time-locked change in firing rate. The remaining 33 cells (58%) showed no changes in firing rate, background activity, somatic receptive field area, or input properties as a result of ureter stimulation. 3. Neurons responding to the 80-mmHg stimulus were further tested with a range of ureter pressures (5-100 mmHg). No responses were evoked by stimuli of < 20 mmHg, and responses observed were proportional to stimulus intensity. Excitatory responses showed a long onset latency (median = 23 s) and long afterdischarges (median = 145 s). 4. All neurons with ureter input had nociceptive somatic inputs. When compared with neurons without ureter input, cells with ureter input were more likely to show background activity (80 vs. 27%) and more likely to have bilateral somatic receptive fields (30 vs. 6%). Neurons with ureter input had higher rates of background activity and larger somatic receptive fields. Ureter stimulation also produced changes in the somatic receptive field area of neurons excited or inhibited by the stimulus, indicating a high degree of plasticity in the ureteric nociceptive pathway. 5. We conclude that the characteristics of the responses of dorsal horn neurons with ureter input to noxious and innocuous ureter stimulation indicate that they receive ureteric input mainly from high-threshold afferents, and that their response properties correlate well with ureteric pain sensation in humans.

Animals↗
PubMed1995

Excitability changes of somatic and viscero-somatic nociceptive reflexes in the decerebrate-spinal rabbit: role of NMDA receptors.

1. Wind-up (frequency-dependent potentiation of the responses of spinal neurones to stimulation of unmyelinated afferents) and other N-methyl-D-aspartate (NMDA) receptor-mediated phenomena have been proposed as key mechanisms underlying persistent pain states. In this study we have compared wind-up in visceral and somatic nociceptive pathways to examine the possible contribution of these mechanisms to visceral pain and hyperalgesia. 2. Experiments were performed on thirteen decerebrate spinalized rabbits. A somato-somatic (SS) reflex (evoked by stimulating skin and muscle afferents from the L2 spinal nerve) and a viscero-somatic (VS) reflex (evoked by stimulating visceral afferents in the splanchnic nerve) were recorded from the L1 spinal nerve. The reflexes consisted of an early (A fibre) and a late (C fibre) component. 3. Conditioning trains of sixteen high intensity electrical stimuli at 1 Hz were applied to the somatic or visceral nerve. These conditioning stimuli did not produce wind-up in the early component of either reflex but evoked powerful wind-up in the late SS reflex (mean percentage of baseline +/- S.E.M., 191 +/- 30%). In contrast wind-up was weak or absent in the late VS reflex (mean percentage of baseline +/- S.E.M., 21 +/- 6%). Conditioning of somatic afferents facilitated both the early and late SS reflex but strongly depressed the early and late VS reflex. Conditioning of visceral afferents had little effect on the early SS reflex, but depressed the early VS reflex and the late components of both reflexes. 4. Intravenous administration (1-10 mg kg-1) of the NMDA receptor antagonist ketamine dose-dependently inhibited the strong wind-up in the late SS reflex and the weak wind-up in the late VS reflex, but also dose-dependently inhibited the early and late components of both baseline reflexes. 5. We conclude that neural mechanisms other than wind-up may underlie the development of visceral pain and hyperalgesia. The present results emphasize the important differences in the processing of somatic and visceral nociceptive input by spinal nociceptive systems and confirm the involvement of NMDA receptors in the spinal processing of nociceptive information.

Animals↗
PubMed1995

Visceral pain: mechanisms of peripheral and central sensitization.

This paper describes the responses of peripheral and central visceral nociceptive systems to acute injury and discusses these observations in relation to the concept of 'pre-emptive analgesia'. Visceral nociceptors are known to respond to injury but are also known to become sensitized to non-noxious stimuli during the inflammatory process that follows intense noxious stimulation. The afferent barrages triggered in visceral nociceptors by the acute injury and the enhanced responses evoked in sensitized nociceptors during the repair process can, in turn, increase the excitability of central nociceptive systems. The maintenance of central hypersensitivity is, however, dependant on the continuing presence of afferent volleys from sensitized nociceptors because the central changes cannot be sustained in the absence of a peripheral drive. Therefore it is proposed that the concept of 'pre-emptive analgesia', as such, has no neurophysiological basis. Any analgesic procedure aimed at reducing postoperative pain must not only prevent the arrival in the CNS of the initial afferent barrage evoked in nociceptive endings but also reduce or eliminate the persistent discharges of sensitized nociceptors during the inflammatory repair process that are critically important for the maintenance of the central pain state.

Analgesia↗
PubMed1994

A psychophysical study of secondary hyperalgesia: evidence for increased pain to input from nociceptors.

Substantial evidence suggests that the hyperalgesia to mechanical stimuli that occurs in an area of uninjured skin surrounding a site of injury (area of secondary hyperalgesia) arises from activity in low-threshold mechanoreceptors (LTMs). In this study, we have investigated if activity in mechanically sensitive nociceptors also contributes to this secondary hyperalgesia. It is known that all woollen fabrics excite LTMs, but that only the prickly ones activate mechanically sensitive nociceptors. Therefore, we have conducted a psychophysical study using a range of prickly and non-prickly woollen fabrics applied to normal and hyperalgesic skin to assess the roles of LTMs and nociceptors in secondary hyperalgesia. We have studied in 10 normal volunteers the sensations of fabric-evoked prickle and pain in normal and hyperalgesic skin. Secondary hyperalgesia was produced by intradermal injection of capsaicin (25 micrograms) into the volar skin of the forearm. Five woollen fabrics (2 non-prickly, 2 prickly and 1 intermediate) were presented, in a blind manner, to the skin before and after the capsaicin injection. The sensation of fabric-evoked prickle was not changed in hyperalgesic skin. On the other hand, little if any pain was evoked by the fabrics when applied to normal skin, but substantial pain was produced by all fabrics when applied to hyperalgesic skin. The pain ratings were graded with the ratings of prickle so that fabrics that evoked the greatest prickle also evoked significantly more pain. The magnitude of pain increased linearly with prickle sensation; the slope of this regression function increased substantially in hyperalgesic skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Development of secondary hyperalgesia following non-painful thermal stimulation of the skin: a psychophysical study in man.

A psychophysical study has been carried out in 10 normal human subjects to examine whether conscious perception of pain is necessary for the development of secondary hyperalgesia. Prolonged thermal stimulation of the skin was applied to the subjects at intensities known to evoke discharges in polymodal nociceptors but insufficient to evoke pain sensations. During this stimulation the development of punctate and of stroking hyperalgesia was examined as was the presence of a skin flare indicative of nociceptor activation. All subjects developed a flare and an area of hyperalgesia following the application of the non-painful heat stimulus. The first change observed in the subjects was the appearance of an area of hyperalgesia to punctate stimuli, followed by flare and by stroking hyperalgesia. The onset of pain was always reported sometime after these events. Statistical analysis of these data for all subjects showed a highly significant difference between the time of onset of pain and the time of onset of any of the other 3 phenomena. Significant differences were also observed between the onset of punctate hyperalgesia and the onsets of flare and of stroking hyperalgesia. No difference was observed between the onset of flare and of stroking hyperalgesia. These results show that cutaneous hyperalgesia can be evoked in normal human subjects by prolonged thermal stimulation of the skin at temperatures that are not perceived as painful. The development of a flare in all subjects simultaneously with stroking hyperalgesia but before the perception of pain suggests that activation of nociceptors is necessary for the hyperalgesia to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Neurons in the rat spinal trigeminal complex driven by corneal nociceptors: receptive-field properties and effects of noxious stimulation of the cornea.

1. A survey of the receptive-field properties of neurons in the spinal trigeminal complex driven by stimulation of corneal afferents has been carried out. The afferent inputs to these neurons from the cornea and from the adjacent skin were studied as well as changes in the excitability of the cells and in the size of their receptive fields after thermal noxious stimulation of the cornea. 2. Single-unit electrophysiological recordings were made in pentobarbitone anesthetized rats from 54 neurons all of which were activated by mechanical stimulation of the ipsilateral cornea. Seventeen of these neurons were activated only by corneal stimulation and the other 37 had an additional cutaneous receptive field in the periorbital skin. Of the 37 neurons with a cutaneous receptive field, 29 were activated exclusively by noxious stimulation of the skin (Class 3) and the remaining 8 were driven by both innocuous and noxious cutaneous stimuli (Class 2). 3. All of the neurons were located in the ventro-lateral area of a region of the spinal trigeminal complex between +0.5 mm and -1.0 mm from the obex. This area corresponds to the most caudal part of subnucleus interpolaris, the transition zone between interpolaris and caudalis and the rostral half of subnucleus caudalis. Most neurons were located in the superficial layers of this part of the spinal trigeminal complex. No differences were observed between the locations of the recording sites of neurons with an exclusive corneal input and those with a corneal and a cutaneous receptive field.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1992

Visceral nociceptors: a new world order?

There has been a long-standing controversy as to whether or not internal organs are innervated by a special category of 'visceral nociceptor'. Recent experimental studies on the afferent supply of some viscera have thrown new light on this issue by demonstrating the presence of several categories of visceral sensory receptor, including high-threshold receptors, 'silent' nociceptors and intensity-encoding receptors. Advances in the understanding of how the CNS processes nociceptive signals have also helped to clarify the issue. The authors of this report, originally having different points of view, present here a common and closer approach to the visceral nociceptor controversy.

Animals↗
PubMed1992

The representation of prolonged and intense, noxious somatic and visceral stimuli in the ventrolateral orbital cortex of the cat.

The responses of single neurones in the ventrolateral orbital (VLO) cortex to noxious pinch, heating of the skin, twisting of the joints and distension of the gall bladder were studied in cats anaesthetized with halothane. Of 60 neurones studied, 44 responded to prolonged (greater than 10 sec) stimuli that were well within the noxious range. Neurones were relatively unresponsive to innocuous stimuli or to the transient application of noxious stimuli. Many single neurones responded to a variety of modalities of noxious stimuli (e.g., skin heating and gall bladder distension). Many neurones studied showed a fluctuating level (5-15 Hz) of ongoing spontaneous activity. Neurones responded with either an increased frequency of spikes (excitation) or an inhibition of spontaneous discharge, irrespective of the source of noxious stimulation. Noxious stimuli delivered simultaneously to two different tissues (e.g., skin and visceral) sometimes produced excitation of the neurone under study, to levels above that produced by the application a noxious stimulus to only one of the tissues. Receptive fields were often large involving both contralateral and ipsilateral areas of the body, as well as both fore and hind limbs. No evidence of somatotopic organization was obtained. The responses of some neurones outlasted the application of the stimuli by many minutes. It is concluded that single neurones in the ventrolateral orbital cortex respond to the prolonged application of intensely noxious stimuli to a variety of body tissues, in a manner that is in keeping with the involvement of this cortical area in both the physiological, autonomic and experiential components of the affective-motivational aspect of pain. Furthermore, from the consequences of lesion studies in man and animals, it is proposed that the activation of cells in the orbital cortex by a variety of noxious stimuli reflects its more general role in the development and maintenance of behaviour in response to negative reinforcement of both social and physical origins.

Animals↗
PubMed1992

Afferent fibres from the guinea-pig ureter: size and peptide content of the dorsal root ganglion cells of origin.

A study was undertaken to determine the segmental organization of the dorsal root ganglion cells which give rise to ureteric primary afferent fibres in the guinea-pig. The size-distribution and peptide content of these dorsal root ganglion cells were examined and compared with a sample of all dorsal root ganglion cells from the same ganglia. Afferent fibres to the guinea-pig ureter were found to arise mainly from dorsal root ganglia L2-L3 and S1-S2. A large contralateral component of the afferent innervation of the ureter was found when either the right or the left ureter was injected with tracer. This amounted to approximately 40% of the total labelled cells. The cross-sectional areas of the dorsal root ganglion cells of ureteric afferents were found to be at the smaller end of the size-range for the whole ganglion. Most (90%) of the cells innervating the ureter were immunoreactive for one of the peptides studies, substance P or calcitonin gene-related peptide, and a large proportion (65%) were immunoreactive for both. This was very different for the ganglia as a whole, where only about 50% of the cells were immunoreactive for either of the peptides and only 14% were immunoreactive for both peptides. These results show a bilateral afferent innervation of the ureter by nerve fibres which, in the vast majority, contain substance P and/or calcitonin gene-related peptide.

Animals↗