Effects of systemic naloxone upon ventrobasal thalamus neuronal responses in arthritic rats

This study deals with the effect of various doses of systemic naloxone (10 μg, 300 μg, 1 mg/kg) upon activities of 21 ventrobasa thalamus neurons recorded in 20 rats rendered arthritic by injection of Freund's adjuvant into the tail. These neurons presented reproducible responses to movement and/or mild lateral pressure on a joint and a joint and were recorded for at least 30 min after naloxone administration. Several neurons (5) were tested with two doses.After intravenous injection of naloxone at the dose of 10 μg/kg (10 cases) there was a rapid decrease of the responses. The maximum effect occurred at 15 min when the mean value expressed as a percentage of the control was 46.20 ± 8.51% (n= 10, P < 0.001). Recovery could be considered as complete at 30 min.At the dose of 300 μg/kg (9 cases), the decrease in the responses was less important, variable from one neuron to another but significant between 5 and 20 min (mean= 67.43 ± 9.00%at20min, n= 7, P < 0.01).At the dose of 1 mg/kg (7 cases), there was no significant modification of the response.Spontaneous firing rate of the neurons was slightly significantly increased after injection of the two highest doses and unmodified after the lowest.The relationship between the depressive effect produced by low doses of naloxone upon the neuronal responses, and the ‘bi-directional’ analgesic-hyperalgesic action of the drug, demonstrated in these suffering rats, is discussed.     

Further evidence for a strong depressive effect of low doses of morphine on VB thalamic neuronal responses (a study on arthritic rats)

The effects of various i.v. morphine doses (30, 100 and 1000 micrograms/kg) were studied upon unitary ventral basal (VB) neuronal responses elicited by joint stimulation in 24 Freund's adjuvant induced arthritic rats. The depressive effect of morphine was significantly dose-related and generally naloxone-reversible; however there were sometimes some difficulties to reverse morphine effect with the lowest dose of naloxone (10 micrograms/kg). The effect of morphine was not significantly different from that obtained in normal rats upon responses of specific nociceptive VB neurons. Although these results do not explain enhancement of morphine analgesia in arthritic rats by comparison with normal rats, they do confirm efficiency of low doses of morphine upon VB neuronal responses elicited by stimuli which induce nociceptive reaction in freely moving animals.     

A comparative analysis of coordinated neuronal activity in the thalamic ventrobasal complex of rats and cats

There are substantial differences in the incidence of inhibitory neurons in the ventrobasal complex of rat and cat thalamus. This marked dissimilarity in neuronal composition suggests that there should be corresponding differences in the orchestration of neural activity in these regions during cutaneous stimulation. To explore this possibility, we conducted a cross-correlation analysis of neuronal activity in the ventroposterolateral (VPL) nucleus of anesthetized rats and cats. Pairs of neurons representing hairy skin were recorded simultaneously with one or two electrodes during air jet stimulation of multiple sites throughout the receptive fields. Cross-correlation histograms indicated that correlated activity among adjacent neurons occurred in three distinct patterns. In one pattern, classified as narrow-unimodal, the discharge of one neuron preceded a discharge in the partner neuron over a narrow interval of time (<5 ms). Narrow-bimodal patterns were characterized by responses in which the temporal order of discharges from the two neurons was variable, but the interspike intervals were always <5 ms. In wide-unimodal patterns, the discharge of one neuron was correlated with subsequent discharges in the partner neuron over a wide interval of time (>5 ms). In rat VPL, two-thirds of the 58 neuron pairs showing correlated responses were characterized by narrow-unimodal responses and nearly one-third of the neuron pairs displayed narrow-bimodal patterns. Only one pair of rat VPL neurons were characterized by a wide-unimodal pattern of coordination. By comparison, half of the 61 adjacent neuron pairs with coordinated responses in cat VPL were characterized by narrow-unimodal patterns. Slightly more than one-third of the correlated neuron pairs had narrow-bimodal patterns, while the remainder (13%) were classified as wide-unimodal responses. Pairs of neurons separated by 340–405 μm discharged synchronously in a pattern that was similar to the temporal relationship expressed in the narrow-bimodal patterns found among adjacent neurons. In both species, the wide-unimodal patterns had the strongest coordinated responses as measured by the correlation coefficient. Although inhibitory relationships did not appear in correlation histograms that had been correlated for stimulus coordination, cross-correlation analysis of the raw spike trains revealed brief (10–40 ms) periods of inhibition that were associated with cat VPL neurons exhibiting wide-unimodal coordination patterns. In rat VPL, most inhibition involved longer (30–60 ms) periods of inhibitory oscillations appearing amidst a much larger rhythmic pattern. These results suggest that correlation patterns transpiring over narrow (<5 ms) time intervals represent the coordination of activity among neighboring thalamocortical relay neurons. By contrast, wide-unimodal patterns appear to represent coordinated activity between a thalamocortical relay cell and an intrinsic inhibitory neuron.     

Heterogeneous axonal arborizations of rat thalamic reticular neurons in the ventrobasal nucleus

The γ-aminobutyric acid (GABA)-containing neurons of the thalamic reticular nucleus (nRt) are a major source of inhibitory innervation in dorsal thalamic nuclei. Individual nRt neurons were intracellularly recorded and labelled in an in vitro rat thalamic slice preparation to investigate their projection into ventrobasal thalamic nuclei (VB). Camera lucida reconstructions of 37 neurons indicated that nRt innervation ranges from a compact, focal projection to a widespread, diffuse projection encompassing large areas of VB. The main axons of 65% of the cells gave rise to intra-nRt collaterals prior to leaving the nucleus and, once within VB, ramified into one of three branching patterns cluster, intermediate, and diffuse. The cluster arborization encompassed a focal region averaging approximately 25,000 μm² and contained a high density of axonal swellings, indicative of a topographic projection. The intermediate structure extended across an area approximately fourfold greater and also contained numerous axonal swellings. The diffuse arborization of nRt neurons covered a large region of VB and contained a relatively low density of axonal swellings. Analysis of somatic size and shape revealed that diffuse arborizations arose from significantly smaller, fusiform-shaped somata. Cytochrome oxidase reactivity or parvalbumin immunoreactivity was used to delineate a discontinuous staining pattern representing thalamic barreloids. The size of a cluster arborization closely approximated that of an individual barreloid. The heterogeneous arborizations from nRt neurons may reflect a dynamic range of inhibitory influences of nRt on dorsal thalamic activity. © 1996 Wiley-Liss, Inc.     

Ultrastructural analysis of GABA-immunoreactive elements in the monkey thalamic ventrobasal complex

This study describes the ventrobasal complex of the primate by using GABA immunocytochemistry at the electron microscopic level. The primate ventrobasal complex has a similar synaptic organization to sensory thalamic nuclei in other species. Two synaptic profiles within the ventrobasal complex contain flattened or pleomorphic synaptic vesicles and are GABA-immunoreactive. F-boutons (= F1 type, Guillery's classification; Guillery: Z. Zellforsch. 96:1-38, '69) are located principally in the extraglomerular neuropil and contain densely packed flattened synaptic vesicles and several elongate mitochondria and establish symmetric (Gray's type II) synaptic contacts. These boutons are not found postsynaptic to any other element and are presynaptic principally to nonimmunoreactive elements that are thought to be thalamocortical relay cell dendrites. PSD-boutons (= F2 type, Guillery's classification) contain a moderate number of flattened or pleomorphic synaptic vesicles and fewer mitochondria than F-boutons. PSD-boutons are found in glomerular and extraglomerular areas of neuropil and establish symmetric synaptic contacts. These boutons are considered to be appendages of interneuron dendrites and are postsynaptic to RL-, RS (Guillery's classification)-, F-, and other PSD-boutons. PSD-boutons are presynaptic to thalamocortical relay neurons and interneuron dendrites including PSD-boutons. Problems in distinguishing F- from PSD-boutons are addressed by comparing immunostained and nonimmunostained material and by the use of serial sections. The majority of synaptic contacts between pleomorphic vesicle-containing profiles appear to be between PSD-boutons and other components of interneurons. Few contacts between F-boutons and local circuit neurons are seen. These data suggest the principal GABAergic input to interneurons in the primate ventrobasal complex is derived from other interneurons.     

Modifications in the responsiveness of rat ventrobasal thalamic neurons at different stages of carrageenin-produced inflammation

The present study was aimed at analyzing the responsiveness of the ventrobasal (VB) thalamic neurons in rats presenting with a hyperalgic carrageenin-produced inflammation. The following were studied: the responses of the same VB neuron, before and 15-145 min after the plantar injection of carrageenin in a part of its receptive field (RF) (acute phase); the responses of VB neurons located in the thalamus contralateral to the hyperalgesic inflamed paw, 24-96 h after the injection (subacute phase); and the effect of a local anesthetic injected in the inflamed paw, and that of an intravenous injection of Aspirin, on neuronal response modifications. Responses of VB neurons initially activated by light tactile stimuli (group 1; n = 4) and by moderate joint stimulation (group 3; n = 4) were not modified in the early period following the carrageenin injection. By contrast, in the first few minutes following the injection. VB neurons exclusively driven by noxious mechanical and thermal stimuli (group 2; n = 23), exhibited a clear enhancement of their responses, which persisted during the observation period. These modifications were also observed for responses obtained from part of the RF remote from the injection site; moreover there was an extension of the RF to areas distant from the injured paw. The local injection of an anesthetic (Xylocaine) in this paw, suppressed the modifications of responses of group 2 neurons, elicited not only from the injected paw, but also from the remote parts of the RF. At this time Aspirin was almost inefficient (even at the dose of 100 mg/kg) on responses of these group 2 neurons. In the subacute phase responses of 72 somatosensory neurons were analyzed. Twenty-five of 72 responded to rapid repetitive light tactile stimulation applied on a small contralateral RF (group 1); their responses were similar to those encountered in a normal situation. Thirty-three of 72 neurons responded to intense mechanical stimuli such as pinches (group 2). For half of them the response characteristics were similar to those described in the normal rat; for the other half responses appeared 'faded': short duration; absence of after-discharge; poor reproducibility. Fourteen of 72 neurons responded to moderate stimulation of the joints, deep tissues and/or surrounding cutaneous areas of the inflamed paw (group 3). Their RF was mostly unilateral, i.e. contralateral to the recording site; the responses were sustained during the stimulation but rarely exhibited after-discharge.(ABSTRACT TRUNCATED AT 400 WORDS)     

Somatic sensory representation in the thalamic ventrobasal complex of the Virginia opossum

The present study was designed to investigate the topographic organization of somatic sensory representation in the thalamic ventrobasal complex (Vb) of the Virginia opossum. Tungsten and stainless steel micro electrodes were used to record the electrical activity of single units or single unit clusters in response to mechanical stimulation of the body surface, and the obtained data were used to construct maps of somatic sensory representation in transverse planes of the ventrobasal complex. The general pattern is similar to that found in eutherian mammals. A relatively large contralateral head and face representation is located throughout the entire anterior-posterior extent of the ventrobasal complex, while a relatively smaller representation of contralateral trunk and limbs is located laterally only in the middle regions of the ventrobasal complex. Representations of middorsal head and trunk are located dorsally while those of limb apices are located ventrally. Activity was also recorded in the posterior nuclear region of the thalamus (Po) and in the subthalamic zona incerta (ZI), and there is a suggestion of topographic organization in these nuclear regions as well.     

Administration of baclofen, a gamma-aminobutyric acid type B agonist in the thalamic ventrobasal complex, attenuates allodynia in monoarthritic rats subjected to the ankle-bend test

gamma-Aminobutyric acid type B (GABAB) receptors are involved in the modulation of neuronal activity in response to chronic noxious input. However, the effect of their activation in chronic inflammatory pain in relay thalamic nuclei such as the ventrobasal complex (VB) is not known. In this study, experimental groups of 2, 4, and 14 days monoarthritic (MA) rats were injected with saline (controls) or baclofen (0.875 microg), a specific GABAB receptor agonist, in the VB contralateral to the inflamed joint, and the ankle-bend test was performed. Ankle-bend scores in control animals were near the maximum and were rather constant throughout the entire experimental period, indicating severe nociception. The same was observed in 2 days MA rats injected with baclofen. In the 4 days MA group, the response to baclofen injection was inconsistent among different animals, whereas, in 14 days MA rats, baclofen caused clear antinociceptive effects. Additionally, a 0.5 microg dose of baclofen was tested in 14 days MA rats, but no effect was observed, whereas a 1.25 mug dose produced visible side effects. Baclofen injections that did not target the VB but reached neighboring nuclei were ineffective in reducing nociception. Data demonstrate that the activation of the GABAB receptors by baclofen in the VB of MA rats leads to a decrease of nociception. Moreover, the response depends on the time course of the disease, suggesting the occurrence of different excitatory states of thalamic VB neurons. In conclusion, GABAB receptors in the VB play an important role in chronic inflammatory pain processing.     

Evidence for central phenomena participating in the changes of responses of ventrobasal thalamic neurons in arthritic rats

In this study performed in the Freund's adjuvant-induced arthritic rat, a local injection of lidocaine in one hind paw strongly depressed the ventrobasal thalamic neuronal responses to mild stimulation of both ankles. In parallel, a behavioral study provided evidence for a bilateral hypoalgesia, tested by the vocalization threshold to paw pressure, after a unilateral anesthetic block. The involvement of central phenomena in the changes of neuronal responsivity described in this model of experimental pain is therefore suggested.     

Tactile responses of hindpaw, forepaw and whisker neurons in the thalamic ventrobasal complex of anesthetized rats

The majority of studies investigating responses of thalamocortical neurons to tactile stimuli have focused on the whisker representation of the rat thalamus: the ventral–posterior–medial nucleus (VPM). To test whether the basic properties of thalamocortical responses to tactile stimuli could be extended to the entire ventrobasal complex, we recorded single neurons from the whisker, forepaw and hindpaw thalamic representations. We performed a systematic analysis of responses to stereotyped tactile stimuli − 500 ms pulses (i.e. ON–OFF stimuli) or 1 ms pulses (i.e. impulsive stimuli) − under two different anesthetics (pentobarbital or urethane). We obtained the following main results: (i) the tuning of cells to ON vs. OFF stimuli displayed a gradient across neurons, so that two-thirds of cells responded more to ON stimuli and one-third responded more to OFF stimuli; (ii) on average, response magnitudes did not differ between ON and OFF stimuli, whereas latencies of response to OFF stimuli were a few milliseconds longer; (iii) latencies of response to ON and OFF stimuli were highly correlated; (iv) responses to impulsive stimuli and ON stimuli showed a strong correlation, whereas the relationship between the responses to impulsive stimuli and OFF stimuli was subtler; (v) unlike ON responses, OFF responses did not decrease when stimuli were moved from the receptive field center to a close location in the excitatory surround. We obtained the same results for hindpaw, forepaw and whisker neurons. Our results support the view of a neurophysiologically homogeneous ventrobasal complex, in which OFF responses participate in the structure of the spatiotemporal receptive field of thalamocortical neurons for tactile stimuli.     

Plasticity of GABA- and glutamate-containing terminals in the mouse thalamic ventrobasal complex deprived of vibrissal afferents: an immunogold-electron microscopic study

GABA and glutamate immunogold staining demonstrated that nerve cells of the thalamic ventrobasal complex (VB) of mice were positive exclusively for glutamate. None of the neuronal perikarya reacted the GABA antibody. By using alternate thin sections of the normal VB, it was also shown that large "specific" somatosensory and small corticothalamic terminals, both of which contained spherical synaptic vesicles, exhibited only glutamate-like immunoreactivity. A third axonal type, containing flat-ovoid synaptic vesicles, stained only for GABA. Seventy-five days after coagulation of the vibrissal follicles in newborn mice, a characteristic multiplication of GABA positive axon terminals was observed. In addition, it was demonstrated that, similarly to modified cortical endings (Hámori et al., J. Comp. Neurol. 254:166-183, '86), many GABA positive terminals appeared as specific afferent endings, replacing the missing "specific" vibrissal afferents. This finding shows a remarkable plasticity of inhibitory GABA axons during developmental synaptogenesis and provides further evidence that the size, location, and the type of attachment of presynaptic terminals are dependent on their postsynaptic target.     

Properties of velocity-mechanosensitive neurons of the cat ventrobasal thalamic nucleus with special reference to the concept of convergence

Neurons in the ventrobasal (VB) thalamic nucleus of lightly anesthetized cats were studied in order to analyze their discharge properties in response to controlled mechanical stimuli. Properties of the vast majority of the neuronal population largely resemble those of peripheral sensitive mechanoreceptors in their response to the velocity and, to a more limited extent, the amplitude component, of skin and hair displacement within restricted receptive fields. Detailed examination reveals some ‘complex’ characteristics suggestive of central integration in about 11% of VB neurons. Complex properties appear to indicate convergent input reflecting receptive field organization, the variety of velocity-related discharges and patterns of inhibition. The rarity of isolated ‘surround’ inhibition and the definition of what constitutes ‘lemniscal’ properties are discussed in the context of these and other related findings.     

Effects of electroacupuncture on thalamic evoked responses recorded from the ventrobasal complex and posterior nuclear group after tooth pulp stimulation in rat.

Effects of electroacupuncture on the thalamic evoked responses following tooth pulp stimulation were investigated in Wistar albino rats. Electroacupuncture stimulation reduced the negative deflection of the responses recorded from the posterior nuclear group more than those recorded from the ventrobasal complex.     

Can tolerance to morphine be induced in arthritic rats?

The effects of acute injections of morphine (0.1-1 mg/kg i.v.) upon vocalization threshold elicited by pressure of the paw were analyzed in normal and arthritic rats, both groups being initially pretreated with calculated doses of morphine. The analgesic effects of morphine were greatly reduced in both groups of chronically morphine-treated rats. The lowest doses (0.1 mg/kg in normal rats; 0.1 and 0.3 mg/kg in arthritic animals) became totally ineffective, while the highest dose (1 mg/kg) elicited a threshold increase only equivalent to that induced by 0.3 mg/kg in non-tolerant chronically vehicle-treated rats. Tolerance to morphine can be induced in rats suffering from arthritis, and appeared to be more complete than in normal rats.     

Inhibition of thalamic ventrobasal complex neurons by glutamate infusion into the thalamic reticular nucleus in rats

In urethane-anesthetized rats a 0.36-mm metallic cannula for infusion was positioned in the somatosensory component of the thalamic reticular nucleus (sTR), where movement of the vibrissae evoked neuronal discharge. Infusion there of 0.125-0.5 microliter of a 50 mM solution of glutamate over a 1-min period suppressed both spontaneous and evoked discharge of neurons in the ventrobasal complex (VB), but only for those which also responded to vibrissal stimulation. VB neurons activated by somatosensory stimuli at other locations were unaffected. Thus, excitation of neurons in sTR inhibits those in VB, but the effect appears to be highly coordinated somatotopically.     

Cingulate gyrus of the cat receives projection fibers from the thalamic region ventral to the ventral border of the ventrobasal complex

Direct projections to the cingulate gyrus from the thalamic region lying just ventrally to the ventral border of the ventrobasal complex (VB) were found in the cat by two sets of experiments that used WGA-HRP (wheat germ agglutinin-horseradish peroxidase conjugate). In the first set of experiments, WGA-HRP was injected into the thalamic region around the ventral border of the VB. When the site of injection involved the thalamic region lying ventrally to the ventral border of the VB at the levels of the caudal two thirds of the VB, the cerebral cortex in the rostral part of the cingulate gyrus ipsilateral to the WGA-HRP injection contained fine HRP-positive granules, which indicated anterograde labeling of axon terminals. These labeled presumed axon terminals were mainly distributed to the superficial part of layer I, deep part of layer II, layer IV, and the most superficial part of layer V in the cingulate cortex. In the second set of experiments, WGA-HRP was injected into the cerebral cortex of the rostral part of the cingulate gyrus. When the site of injection involved the region of the cingulate gyrus, where presumed axon terminals had been labeled in the first set of experiments, the thalamic region just ventral to the ventral margin of the caudal two-thirds of the VB ipsilateral to the WGA-HRP injection contained neuronal cell bodies labeled retrogradely. The results indicate that some neurons that are located in the thalamic region just ventral to the ventral border of the caudal two-thirds of the VB send their axons to the cerebral cortex in the rostral part of the cingulate gyrus. The possible significance of the thalamocingulate projection found in the present study is discussed with relation to nociceptive behavior and function.     

Responses of thalamic and hypothalamic neurons to scrotal warming in rats: Non-specific responses?

Activities of thalamic and hypothalamic neurons in response to scrotal temperature change were investigated in urethanized (1.2-1.5 g/kg) rats with special attention to changes in cortical electroencephalogram (EEG). Somatosensory relay neurons were identified electrophysiologically in the ventrobasal complex (VB) of the thalamus. These neurons had tactile receptive fields in areas outside the scrotum. Forty out of 44 of these neurons responded to scrotal warming by increase in firing rate. The responses occurred abruptly at threshold temperatures ranging from 31 to 40 degrees C (switching response) with simultaneous changes in EEG from high to low voltages (desynchronization). In both the thalamus and the hypothalamus, neurons excited or inhibited by scrotal warming were also excited or inhibited, respectively, by noxious stimulation that produced EEG desynchronization. Neurons showing no response to scrotal warming were not affected by noxious stimulation. In deeply anesthetized (2.5 g/kg urethane) rats, VB relay neurons responded to tactile stimulation of their receptive fields, but scrotal warming produced no change in either EEG or activities of thalamic and hypothalamic neurons. These facts suggest that the responses of thalamic and hypothalamic neurons to scrotal warming may be 'non-specific'. Most thalamic and hypothalamic neurons showing switching responses did not appear to mediate specific information concerning scrotal skin temperature.     

Differential depressive action of two μ and δ opioid ligands on neuronal responses to noxious stimuli in the thalamic ventrobasal complex of rat

In the present investigation the effects of selective agonists for μ (Tyr- -Ala-Me-Phe-Gly-ol (DAGO)) and δ (Tyr- -Thr-Gly-Phe-Leu-Thr (DTLET)) opioid receptors on neuronal activities induced by noxious cutaneous stimuli in the rat ventrobasal (VB) thalamus were analyzed. The two agonists produced a clear depressive action on thermal as well as mechanical noxious stimuli. The depressive action of DTLET (3 mg/kg i.v.) was lower and of shorter duration than that of DAGO (2 mg/kg i.v.). However, this effect is unambiguously related to the selective stimulation of opioid receptors since a consistent effect was also observed for a dose as low as 1.5 mg/kg i.v. of DTLET. Moreover, DTLET effect needs a high concentration of naloxone (0.5 mg/kg i.v.) to be reversed, while DAGO effect is totally reversed with 0.1 mg/kg i.v.     

Deformed dendrites and reduced spine numbers on ectopic neurones in the hippocampus of rats exposed to methylazoxymethanol-acetate

Summary Clusters of ectopic neurones appeared in the hippocampus of rat offspring which were exposed to the alkylating neurotoxin methylazoxymethanolacetate (MAMac) during foetal development. The offspring were 30 and 60 days old when their brains were removed and prepared by the Golgi-Cox procedure outlined by Sholl (1953). Reductions in the number of dendritic branches, changes in apical dendritic lengths, abnormalities in the shapes of the dendritic shafts, and significant diminution in spine numbers were observed in ectopic neurones. The significance of these pathological alterations in dendritic morphology is discussed with special reference to the findings of an earlier study which revealed that afferent axons terminate upon ectopic neurones in an abnormal way.Aided by the N.H. and M.R.C. of Australia     

Dose-dependent analgesic and hyperalgesic effects of systemic naloxone in arthritic rats

The effects of various i.v. naloxone doses (10 μg, 300 μg, 600 μg, 1 mg/kg) were studied upon vocalization threshold to foot-pressure in 30 normal rats and 70 rats with Freund's adjuvant-induced arthritis.In arthritic rats, the lowest naloxone doses yielded a clear increase in pressure required to trigger vocalization (i.e. were analgesic) while the highest dose (1 mg/kg) was hyperalgesic.In normal rats, naloxone never induced significant changes in the vocalization threshold.