[JSRV (jaagsiekte sheep retrovirus) and ovine pulmonary carcinoma]. / JSRV (jaagsiekte sheep retrovirus) et cancer du poumon associé chez le mouton.

JSRV (jaagsiekte sheep retrovirus) is a betaretrovirus, infecting small ruminants. This virus is responsible for the development of pulmonary adenocarcinoma, by the transformation of epithelial cells of the bronchioli and alveoli. This animal cancer is related to human bronchioloalveolar cancer (BAC), a specific form of human lung cancer for which a viral etiology has been proposed for several decades. In small ruminants JSRV interacts with the cells through the Hyal2 receptor. JSRV genome is simple and does not contain already known oncogene. It is now well established that the envelope protein is oncogenic by itself, via the cytoplasmic domain of the transmembrane glycoprotein and some domains of the surface glycoprotein. Activation of the PI3K/Akt and MAPK pathways participates to the envelope-induced transformation. The tumour development is associated with telomerase activation.

Painful sensation induced by a thermal cutaneous stimulus.

This review emphasizes how little we know about pain induced by a thermal stimulus. The study of the intensity of pain evoked by heat is relatively exhaustive: the influence of various local, stimulus-dependent or general factors upon threshold values has been well studied, as has the relation between pain and stimulus intensities. On the contrary, few studies have used very cold stimuli, since highly efficient stimulators allowing accurate control of the stimulus parameters have been obtainable only recently. Only the influence of stimulation area and stimulation rate on cold pain thresholds have been studied. Moreover, old results obtained on pain quality cannot be used since the conditions of stimulation were not specified or not controlled accurately. It is only known that stimulus duration and stimulation area are determinant for thermal pain quality. There is still much work to be done in this field. All the more so as this type of study is absolutely necessary for the understanding of pain mechanisms--it describes what must be explained by the function of the nervous system. We have seen that at the periphery the intensity of heat pain is coded by the response of polymodal nociceptors, mechanothermal nociceptors, thermal nociceptors and possibly by the paradoxical discharge of cold receptors. If the stimulus is lower than 45 degrees C the activity of certain heat receptors comes into play. Although we lack information which would allow confirmation of this as a fact it seems likely that the activity of polymodal nociceptors, cold mechanothermal nociceptors and possibly certain cold receptors sensitive to very low temperatures code cold pain. These nociceptive impulses carried by A delta and C fibers reach the dorsal horn of the spinal cord through the dorsal roots. They are notably at the origin of the activation of the neurons in Rexed's layers I, V and VIII which are to a large extent at the origin of the spinothalamic and spinoreticulothalamic tracks [21,115,168] moving in the anterolateral quadrant of the spinal cord. At supraspinal level, the thermal information reappears in the reticular formation; there it appears to be solely relative to the pain threshold and not to the intensity of a supraliminary stimulus [55]. In the posterior group of nuclei [134] and the ventroposterolateral nucleus of the thalamus [103], on the contrary, the activity of the neurons reflects the intensity of the stimulation. It has been proved that the neurons of the ventroposterolateral nucleus project onto the SI cortex [103].(ABSTRACT TRUNCATED AT 400 WORDS)

Relationship between noxious cold stimuli and the magnitude of pain sensation in man.

Nine healthy subjects received noxious cold stimulations at 20, 15, 10, 5 and 0 degrees C on the thenar eminence of both hands. Each stimulus lasted 30 sec. At the end of the stimulus, subject estimated pain intensity on a scale graduated from 0 (no pain) to 10 (intolerable pain). The results showed that the intensity of cold pain and that of the stimulus are linearly correlated (Spearman test P less than 0.001). Cold pain obeys Stevens' law with an exponent equal to one.

Auditory efferents involved in speech-in-noise intelligibility.

Following studies proposing that medial olivocochlear efferents might be involved in the processing of complex signals in noise, we tested the involvement of efferent feedback in speech-in-noise intelligibility. Two approaches were used: measures of speech-in-noise intelligibility in vestibular neurotomized patients with cut efferents and comparison with normal hearing subjects; and correlations between effectiveness of olivocochlear feedback, assessed by contralateral suppression of otoacoustic emissions and speech-in-noise intelligibility in normal subjects. Contralateral noise improved speech-in-noise intelligibility in normal ears. This improvement, which was almost absent in de-efferented ears of vestibular neurotomized patients, was correlated with the strength of the olivocochlear feedback. Together, these results suggest that olivocochlear efferents play an antimasking role in speech perception in noisy environments.

A selective imaging of tinnitus.

We selectively imaged the neural correlates of tinnitus, by contrasting a condition with no phantom auditory sensation with a condition during which tinnitus is present, using a rare form of tinnitus elicited by eye movements. Using positron emission tomography (PET), we demonstrate that phantom auditory sensation increases regional cerebral blood flow bilaterally in temporo-parietal association auditory areas but not in the primary auditory cortex. These results confirm that conscious perception does not necessarily require activation in primary areas and suggest that the perceptual qualities of tinnitus, e.g. intensity, frequency and spatial localization, are represented in temporo-parietal regions. Activation in these regions is compatible with cortical processing of ascending auditory messages generated at subcortical levels.

Pregnancy-induced increase of spinal cord peptide concentrations in rats.

Tissue peptide concentrations of immunoreactive vasoactive intestinal peptide, somatostatin, substance P and cholecystokinin were measured by radioimmunoassay in undivided cervical, thoracic, lumbar and sacral segments of spinal cords from female Sprague Dawley rats either non pregnant or sacrificed at day 7, 14, 21, and 22 of pregnancy. Non pregnant animals showed for all peptides significant decreasing sacro-cervical gradients of tissue concentrations. Pregnancy was associated with significant rises of immunoreactive somatostatin concentration at the sacral level, and of immunoreactive VIP in the four segments tested. Peak values were recorded between day 14 and day 21, with a brisk decrease of VIP, but not of somatostatin, concentration on day 22. Sacrocervical gradients followed a biphasic increase, reaching a maximum on day 22. The concentrations of immunoreactive substance P and cholecystokinin remained stable throughout pregnancy. The present results suggest that the somatostatinergic and VIPergic structures stored in, or projecting to, the sacral autonomic nuclei are involved in the control of the anatomical and/or physiological modifications of the female genital tract during pregnancy.

Peptide immunocytochemistry in afferent neurons from lower gut in rats.

Several peptides were detected in primary sensory neurons located in nodose and dorsal root ganglia and projecting from rat cecum and rectosigmoid, through a combination of retrograde staining by the fluorescent tracer DY-2HCl and of the immunofluorescent procedure of Coons. The three larger cell populations thus identified stored immunoreactive components respectively similar to calcitonin gene-related peptide (CGRP), substance P (SP), and a peptide related to peptide histidine methionine (PHM). The later immunoreactivity consisted of a single molecular form with an apparent molecular weight smaller than PHM itself. Fewer cells contained components immunologically similar to somatostatin 14 (ST14), to the 1-14 N-terminal sequence of somatostatin 28 (1-14 S28), and to neuropeptide Y (NPY). Neonatal treatment with capsaicin resulted in a drastic reduction of immunoreactivity for SP, PHM, ST14, 1-14 S28, and in a partial reduction of CGRP-like positive perikarya. These results demonstrate that several peptides are potentially involved in the sensory innervation of the lower gut in rat.

Spinal and intestinal levels of substance P, calcitonin gene-related peptide and vasoactive intestinal polypeptide following perendoscopic injection of formalin in rat colonic wall.

Acute inflammation of the colonic wall was induced by perendoscopic injection of formalin in rats. As compared to control animals (no endoscopy, no injection), the procedure was followed by a marked reduction of immunoreactive substance P, calcitonin gene-related peptide and vasoactive intestinal peptide concentrations in rectosigmoid wall. Tissue substance P concentration in the spinal cord, at the level of afferent projection, increased at the same time. The three peptides tested are thus likely to be involved in the pathophysiology of acute intestinal inflammation. In addition, substance P may play a role in the transmission of nociceptive signals from the inflamed colonic segment.

Substance P-, somatostatin-, vasoactive intestinal peptide- and cholecystokinin-like levels in the spinal cord of polyarthritic rats.

Substance P-, somatostatin-, vasoactive intestinal polypeptide- and cholecystokinin-like levels were measured in lumbar dorsal and ventral cord of polyarthritic rats and compared with those obtained in vehicle-treated rats taken as controls. Polyarthritis decreased substance P concentration in lumbar ventral cord and increased cholecystokinin level in lumbar dorsal cord, while the other two peptides did not show any change. The results are discussed in relation to immunohistochemical data found in the literature.

Evidence of a medial olivocochlear involvement in contralateral suppression of otoacoustic emissions in humans.

Otoacoustic emissions (OAEs) evoked by click stimuli were recorded in both ears of 20 normal human subjects, in the presence and absence of a contralateral masking broad band noise. No difference in the amplitude of OAE suppression was noted between the first tested ear and the second one. In addition, 20 pathological subjects were tested according to the same protocol. Ten of them belonged to a group of patients whose vestibular nerve was sectioned on one side to relieve incapacitating vertigo and thus represented a group in whom olivocochlear efferents were severed. A great reduction of suppression observed in the operated ear suggested that olivocochlear efferent fibers are necessary to obtain a full suppressive effect. Three of the pathological subjects were patients who had undergone a decompression of the facial nerve which necessitated the same surgical approach as vestibular neurotomy, but without any section of vestibular fibers. This surgical control group demonstrated that the surgical act by itself cannot explain the difference observed in the neurotomized group. Finally, seven of the pathological subjects were patients with Bell's palsy, which paralyses the facial nerve and abolishes the stapedial reflex. No suppression difference was observed between healthy ears and ears without stapedial reflex. Therefore, it appeared that the stapedial reflex was not involved in the contralateral suppression of EOAEs. However, as the tensor tympani muscle remained functional in these patients, its involvement in the suppressive effect cannot be excluded.

Antinociceptive effects of oral clonidine and S12813-4 in acute colon inflammation in rats.

Acute colonic inflammation was induced by perendoscopic injection of 50 microleters of dilute formalin (5%) in the depth of the colonic wall (c.w.) in rats. Compared to saline injection, the procedure was followed by nociceptive behaviors from which visceral nociception was quantified. The alpha 2-adrenoceptor agonist, clonidine 2-[2,6-dichlorophenylamine]-2-imidazole hydrochloride (75, 150 and 300 mg/kg), administered orally 15 min after c.w. injection of formalin significantly reduced the nociceptive responses at the high dose only. However, when administered 30 min prior to nociceptive stimulation, the compound exhibited an antinociceptive effect at the three doses. A novel analgesic, the compound "S12813-4' 3-[2-(4-phenylpiperazine-1-yl)-ethyl]-2-oxo-2,3-dihydro-oxazolo[b] pyridine, chlorydrate (10, 30 and 90 mg/kg), given orally displayed antinociceptive effects whatever the administration schedule, before or after c.w. injection of formalin. The antinociceptive effect of S12813-4 (30 mg/kg given orally) was prevented by subcutaneous (s.c.) injection of yohimbine or idazoxan (1 mg/kg). We conclude that visceral nociception elicited by formalin-induced colonic inflammation is attenuated by clonidine and S12813-4. The pharmacological profiles of the two compounds and the inhibition of the antinociceptive effect of S12813-4 by yohimbine and idazoxan suggest that noradrenergic mechanisms are involved in the transmission and/or modulation of the nociceptive influx arising from the inflamed colon.

Towards an objectification by classification of tinnitus.

OBJECTIVE: The objectives of this study are to identify the presence of tinnitus and classify its different forms, in terms of changes in noise. METHODS: Late auditory evoked responses (LAERs) were recorded from Fz in response to 1000 Hz tone bursts of various intensities, in 13 tinnitus-free subjects and in 25 tinnitus sufferers (16 bilateral and 9 unilateral tinnitus sufferers). A classification of different forms of tinnitus, in terms of changes in noise, was also undertaken. N1-P2 component amplitudes and N1 and P2 latencies were measured. RESULTS: Objective identification of the affected ear in unilateral tinnitus sufferers was found feasible on the basis of N1-P2 intensity-dependence and N1-P2 amplitude. The bilateral tinnitus group was found to differ from controls by greater intensity-dependence of the N1-P2 component and shorter N1 latency. These characteristics varied with tinnitus type: a classification on the basis of intensity-dependence and latencies proved feasible. The group of patients showing improved tinnitus in noise had greater intensity-dependence and longer N1 latency than did the group showing aggravated tinnitus in noise. CONCLUSIONS: Data are discussed in light of the inhibitory role of frontal cortex on the sensory inputs and the modulatory function of central serotonergic system on the processing of auditory information.

Response of cat skin mechanothermal nociceptors to cold stimulation.

In the cat skin, the activity of 5 mechanothermal nociceptors has been studied to cold nociceptive stimuli. The frequency of discharge is very low (maximum of 2.0 Hz). The repetition of very cold stimulations decreased the discharge threshold of these receptors. After -5 degrees C stimulus, the mechanothermal nociceptors were completely inhibited during 3 to 7 minutes. These mechanothermal nociceptors should have an important function in cold pain.

Capsaicin in adult frogs: effects on nociceptive responses to cutaneous stimuli and on nervous tissue concentrations of immunoreactive substance P, somatostatin and cholecystokinin.

Adult frogs (Rana esculenta) were given subcutaneous injections of 10, 20, 30, 50 and 100 mg/kg capsaicin in sequential order over 5 days, or the vehicle only. The nociceptive thresholds to electrical, thermal and chemical stimuli were measured before, and 1, 5 and 24 h after each injection. Capsaicin was followed by a dose-related reduction of nociceptive responses to all stimuli, but these effects lasted for only 1-5 h after the given injection. Water/acetic extracts of undivided brains and spinal cords were prepared at the corresponding time periods for the radioimmunoassay of peptides. Spinal cord concentrations of immunoreactive substance P were essentially unaffected by capsaicin, while those of immunoreactive somatostatin were significantly increased after the second for fourth injections (20, 30 and 50 mg/kg) of capsaicin. Brain extracts showed an increase of somatostatin and substance P concentrations after the dose of 50 mg/kg. In an additional experiment, immunoreactive substance P, somatostatin and cholecystokinin were measured in tissue samples taken at 2 and 10 min, and 1, 5 and 24 h after a single dose of either 50 mg/kg capsaicin or the vehicle. The only significant effect of capsaicin was an increase of immunoreactive somatostatin concentration in brain homogenates at 5 h, while the vehicle in itself elicited major variations of all three peptides in spinal cord and/or brain. These results indicate that capsaicin reduces the nociceptive responses to cutaneous stimuli in adult frogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic lumbar intrathecal catheterization in the rat with reduced-length spinal compression.

The present paper describes an original technique, chronic lumbar catheterization of the subarachnoidal space in the rat. Introducing the catheter into the rachis directly at lumbar level reduces the length of the intrathecal catheter and, consequently, the extent of spinal cord compression. The validity of the technique is proved by the dose related effect obtained after morphine injections and the staining of the only spinal part of the central nervous system after blue-dye injections.

Effect of contralateral sound stimulation on the distortion product 2f1-f2 in humans: evidence of a frequency specificity.

The frequency characteristics of the suppression by contralateral stimulations, of the cubic 2f1-f2 distortion products (DPOAEs), were studied during 63 sessions performed in 39 humans with normal hearing. Each session consisted of exposure to five successive series of randomized contralateral NBN frequencies centered between 0.25 and 8 kHz, while measuring 2f1-f2 set at one of the four studied frequencies, i.e., 1, 2, 3 or 5 kHz. For each value of 2f1-f2, analysis of variance and Student's t-test were used in order to indicate and, if necessary, to localize, a possible significant frequency specificity. Results showed that the suppression exerted on 2f1-f2 DPOAEs by contralateral sound stimulation, is frequency specific, at least for middle frequencies of 1 and 2 kHz. The frequency specificity is specially marked when 2f1-f2 = 1 kHz with contralateral NBN central frequencies around 1 kHz. When 2f1-f2 = 2 kHz, central frequencies which induced a significant suppressive effect include frequencies around 2 kHz and also lower frequencies around 1 kHz. These observations support the interpretation that the suppression of the DPOAE is mediated by the medial olivo-cochlear efferent system.

An auditory negative after-image as a human model of tinnitus.

The Zwicker tone (ZT) is an auditory after-image, i.e. a tonal sensation that occurs following the presentation of notched noise. In the present study, the hypothesis that neural lateral inhibition is involved in the generation of this auditory illusion was investigated in humans through differences in perceptual detection thresholds measured following broadband noise, notched noise, and low-pass noise stimulation. The detection thresholds were measured using probe tones at several frequencies, within as well as outside the suppressed frequency range of the notched noise, and below as well as above the corner frequency of the low-pass noise. Thresholds measured after broadband noise using a sequence of four 130-ms probe tones (with a 130-ms inter-burst interval) proved to be significantly smaller that those measured using the same probe tones after notched noise at frequencies falling within the notch, but larger for frequencies on the outer edges of the noise. Thresholds measured following low-pass noise using the same sequence of probe tones were found to be smaller at frequencies slightly above the corner, but larger at lower, neighboring frequencies. This pattern of results is consistent with the hypothesis that the changes in auditory sensitivity induced by stimuli containing sharp spectral contrasts reflect lateral inhibition processes in the auditory system. The potential implications of these findings for the understanding of the mechanisms underlying the generation of auditory illusions like the ZT or tinnitus are discussed.

Suppression of otoacoustic emission is unchanged after several minutes of contralateral acoustic stimulation.

The influence of variable durations of contralateral acoustic stimulation on the suppression of click-evoked otoacoustic emissions was investigated in order to determine whether olivocochlear efferent fibers are equally effective whatever the acoustical stimulation duration or if they show fatigue. The suppression effect was measured for contralateral stimulus durations ranging from 10 to 180 s prior to the onset of otoacoustic emission recording, and continuing throughout the recording time (60 s). No significant stimulus duration effect was found.

Perceptual correlates of neural plasticity related to spontaneous otoacoustic emissions?

The inner ear contains receptor cells that oscillate spontaneously, generating waves that propagate backward in the cochlea, ultimately causing sound to be radiated into the ear canal--the spontaneous otoacoustic emissions (SOAEs). Except in rare conditions, these internally generated signals appear to go unheard. The intensity of SOAEs admittedly hovers near the threshold of detection, but they are essentially continuous and perhaps last a lifetime. The hypothesis is tested that the frequency difference limen (DL(F)) is affected by SOAEs. The results show that the DL(F) systematically improves near SOAE frequencies, determined ipsi- or contralaterally to the SOAEs, arguing for a central effect. The results are discussed in the context of central plasticity.