Biomedical subjects

D Lima

Publications and source records attributed to D Lima.

At least 19 recordsLinked to original sources

PubMed2007

Orbitofrontal cortex lesions disrupt risk assessment in a novel serial decision-making task for rats.

Neurobiological mechanisms of decision-making have been shown to be modulated by a number of frontal brain regions. Among those areas, the orbitofrontal cortex (OFC) is thought to play an important role in the decision of behavioral actions when faced with alternative options of ambiguous outcome. Here we present a novel neurobehavioral task to study affective decision-making in the rat, based on evaluation of consecutive choices between two levers associated with rewards of different value and probability. Two groups of animals were studied; a sham control group (n=6) and an OFC-lesioned group (n=7). In the first 30 trials both groups had similar preference patterns but at the end of the 90 trials of the task both groups developed specific preferences. The control group systematically preferred the lever associated with smaller but more reliable rewards (low risk lever) while the OFC lesion group preferred the high risk lever (index of preference of 0.21+/-0.21 vs. -0.45+/-0.10; t-test, P<0.05). Analysis of choice persistence (i.e. choosing the same lever in consecutive trials) suggests that the OFC-lesioned group became less sensitive to risk, seeking large rewards irrespective of their success probability.

Analysis of Variance↗

PubMed2006

Secondary hyperalgesia in the monoarthritic rat is mediated by GABAB and NK1 receptors of spinal dorsal horn neurons: a behavior and c-fos study.

Secondary hyperalgesia in the monoarthritic rat is accompanied by a decrease in nociceptive activation of spinal neurons expressing GABA(B) receptors and by the opposite effect in the cells expressing neurokinin 1 (NK1)-receptors. In order to ascertain the relative role of each receptor, the effects of intrathecal administration of SP-saporin (SP-SAP), baclofen or both were evaluated, using a model of secondary hyperalgesia that consists of mechanical stimulation of the hindlimb skin close to an inflamed joint. Four days after the induction of monoarthritis by intraarticular injection of Complete Freund's Adjuvant (CFA), a cannula was implanted at T(13)-L(1) level and 10 microl of saline or SP-SAP (10(-6) M) were intrathecally (i.t.) injected. Fourteen days after CFA-injection, half of the animals from each group received i.t. injections of 10 microl saline and the remainder were injected with the same volume of baclofen (1 microg). Ten minutes later, the animals were behaviorally evaluated by the von Frey test or submitted to noxious mechanical stimulation to analyze c-fos expression. The von Frey thresholds increased after the treatments, but more pronouncedly after baclofen or SP-SAP plus baclofen. In segments L(2)-L(3), the spinal area that receives input from the stimulated skin close to the inflamed joint, the numbers of Fos-immunoreactive neurons were reduced after the three treatments both in the superficial and deep dorsal horn. In segments T(13)-L(1), the numbers of Fos-immunoreactive neurons were significantly reduced after treatment with SP-SAP plus baclofen in both dorsal horn regions, and in the deep dorsal horn after baclofen treatment. We conclude that both GABA(B) and NK1 receptors of spinal dorsal horn neurons participate in secondary hyperalgesia in the monoarthritic rat, although the decrease in GABA inhibition appears to play a more important role than the increase in SP-mediated effects.

Animals↗

PubMed2006

Nonlinear fingering dynamics of reaction-diffusion acidity fronts: self-similar scaling and influence of differential diffusion.

Nonlinear interactions between chemical reactions and buoyancy-driven Rayleigh-Taylor instability of reaction-diffusion acidity fronts of the chlorite-tetrathionate (CT) reaction are studied theoretically in a vertical Hele-Shaw cell or a porous medium. To do so, we perform a numerical integration of a two-variable reaction-diffusion model of the CT system coupled through an advection term to Darcy's law ruling the evolution of the velocity field of the fluid. The fingering dynamics of these chemical fronts is characterized by the appearance of several fingers at onset. These fingers then undergo coarsening and eventually merge to form one single symmetric finger. We study this asymptotic dynamics as a function of the three dimensionless parameters of the problem, i.e., the Damkohler number Da, the diffusivity ratio delta of the two chemical species, and the Rayleigh number Ra constructed here on the basis of the width L(y) of the system. For moderate values of Ra, the asymptotic single finger is shown to have self-similar scaling properties while above a given value of Ra, which depends on the other values of the parameters, tip splitting comes into play. Increasing the difference of diffusivities of the two chemical species (i.e., increasing delta) leads to more efficient coarsening and smaller asymptotic fingers. Experimental procedures to verify our predictions are proposed.

Journal Article↗

PubMed2005

Differential expression of NK1 and GABAB receptors in spinal neurones projecting to antinociceptive or pronociceptive medullary centres.

The balance between excitatory and inhibitory input exerted upon spinal cord neurones that belong to spinofugal pathways determines the ultimate type of information transmitted to the brain. We compared the relative expression of NK1 and GABAB receptors in two spinomedullary pathways targeting an antinociceptive area and a pronociceptive centre, respectively, the lateral part of the caudal ventrolateral medulla (VLMlat) and the dorsal reticular nucleus (DRt). Spinal cord sections of rats injected in the VLMlat or DRt with the retrograde tracer cholera toxin subunit B were triple-immunoreacted for the tracer, NK1 receptors and GABAB receptors. The dorsal horn neurones labelled from the VLMlat mainly co-localized the two receptors while those labelled from the DRt mainly expressed GABAB receptors, which was particularly evident in neurones of laminae IV-V. The morphological classification of lamina I neurones projecting to the VLMlat showed that fusiform, flattened and pyramidal cells mainly co-localized NK1 and GABAB receptors. As to lamina I neurones projecting to the DRt, multipolar neurones mainly expressed GABAB receptors while the majority of flattened and pyramidal neurones co-localized NK1 and GABAB receptors. The present results suggest that the expression of NK1 and GABAB receptors varies in neurones participating to different spinofugal pathways. The importance of the present findings in the knowledge of the endogenous supraspinal pain control system is discussed.

Animals↗

PubMed2005

Imbalance between the expression of NK1 and GABAB receptors in nociceptive spinal neurons during secondary hyperalgesia: a c-Fos study in the monoarthritic rat.

The neurochemical changes that operate in nociceptive spinal cord circuits during secondary hyperalgesia are largely unknown, in particular with respect to the balance between excitatory and inhibitory neurotransmission. In this study we evaluated the expression of NK1 and GABA(B) receptors in nociceptive spinal neurons in a model of secondary hyperalgesia consisting of noxious mechanical stimulation of the hindlimb skin close to a joint chronically inflamed by complete Freund's adjuvant. In spinal segments receiving input from that skin area, Fos-immunodetection was combined with immunocytochemistry for NK1 receptors, GABA(B) receptors or both receptors. In control and monoarthritic animals, neurons double-labeled for Fos and each receptor occurred mainly in laminae I and IV-V. In lamina I, the percentage of NK1 neurons expressing Fos was higher in monoarthritics while lower percentages of GABA(B) neurons expressed Fos. The percentage of Fos-positive cells expressing NK1 immunoreaction did not change in monoarthritics but that of Fos cells with GABA(B) immunoreaction was lower in these animals. In laminae IV-V, a large increase in Fos expression was detected in monoarthritic rats but the relative proportions of Fos-positive neurons expressing each receptor were similar in the two groups. Co-localization of NK1 and GABA(B) receptors occurred only in lamina I neurons in both experimental groups with no differences between control and monoarthritic animals in the percentages of Fos-positive neurons that expressed the receptors. Considering the participation of lamina I neurons bearing NK1 and GABA(B) receptors in several spinofugal systems, it is possible that the imbalance between excitatory and inhibitory actions exerted, respectively, by substance P and GABA may subserve secondary hyperalgesia by increasing ascending transmission of nociceptive input.

Animals↗

PubMed2004

Convective instability in protein crystal growth.

The conditions for the onset of convection during protein crystalization from a solution are studied theoretically on the basis of diffusion-convection evolution equations for the concentrations coupled to the Navier-Stokes equation describing the flow velocity. We consider that the density of the solution depends on the concentration of two species, namely, a protein and a precipitating agent, a salt. While the protein is crystallized at the crystal/solution interface, the salt is rejected, and these mechanisms are described by means of boundary conditions for the interface. We find the base profiles for both protein and salt concentrations and perform a linear stability analysis of this basic state with regard to buoyancy induced perturbations. This gives information on the critical diameter of capillaries above which convection may be observed, as well as on the influence of the speed of growth V of the crystal interface on the stability of the system. Numerical integration of the model shows good agreement with the predictions of the linear stability analysis.

Animals↗

PubMed2004

Alternative splicing of parathyroid hormone-related protein mRNA: expression and stability.

Parathyroid hormone-related protein (PTHrP) is a multifunctional protein that is often dysregulated in cancer. The human PTHrP gene is alternatively spliced into three isoforms, each with a unique 3'-untranslated region (3'-UTR), encoding 139, 173 and 141 amino acid proteins. The regulation of PTHrP mRNA isoform expression has not been completely elucidated, but it may be affected by transforming growth factor-beta1 (TGF-beta1). In this study, we examined differences in the PTHrP mRNA isoform expression in two squamous carcinoma cell lines (SCC2/88 and HARA), an immortalized keratinocyte cell line (HaCaT), and spontaneous human lung cancer with adjacent normal tissue. In addition, the effect of TGF-beta1 on PTHrP mRNA isoform expression and stability was examined. Cell-type specific expression of PTHrP mRNA isoforms occurred between the various cell lines, normal human lung, and immortalized human keratinocytes (HaCaT). PTHrP isoform expression pattern was significantly altered between normal lung tissue and the adjacent lung cancer. In vitro studies revealed that TGF-beta1 differentially altered the mRNA steady-state levels and mRNA stability of the PTHrP isoforms. Protein-RNA binding studies identified different proteins binding to the 3'-UTR of the PTHrP isoforms (139) and (141), which may be important in the differential mRNA stability and response to cytokines between the PTHrP isoforms. The data demonstrate that there is cell-type specific expression of PTHrP mRNA isoforms, and disruption of the normal regulation during cancer progression may in part be associated with TGF-beta1-induced changes in PTHrP mRNA isoform expression and stability.

3' Untranslated Regions↗

PubMed2003

Brain afferents to the lateral caudal ventrolateral medulla: a retrograde and anterograde tracing study in the rat.

The ventrolateral medulla (VLM) modulates autonomic functions, motor reactions and pain responses. The lateralmost part of the caudal VLM (VLMlat) was recently shown to be the VLM area responsible for pain modulation. In the present study, the brain sources of VLMlat afferent fibers were determined by tract-tracing techniques. Following injection of cholera toxin subunit B into the VLMlat, retrogradely labeled neurons in the forebrain occurred at the somatosensory, insular, motor, limbic and infralimbic cortices, and at the central amygdaloid nucleus. Retrogradely labeled neurons in diencephalic regions were observed in the lateral hypothalamus, posterior hypothalamus and paraventricular nucleus. In the brainstem, retrograde labeling occurred at the periaqueductal gray, red nucleus, parabrachial area, nucleus raphe magnus, nucleus tractus solitarii, lateral reticular nucleus and dorsal and ventral medullary reticular formation. In the cerebellum, retrogradely labeled neurons occurred at the lateral nucleus. Following injections of the anterograde tracer biotinylated dextran amine (BDA) into the lateral hypothalamus or paraventricular nucleus, anterogradely labeled fibers were mainly observed in the VLMlat. Injections of BDA into the periaqueductal gray, red nucleus or lateral nucleus of the cerebellum resulted in anterograde labeling in the VLMlat and lateral reticular nucleus. The present study gives an account of the brain regions putatively involved in triggering the modulatory actions elicited from the VLMlat. These include areas committed to somatosensory processing, autonomic control, somatic and visceral motor activity and affective reactions. The findings suggest that the VLMlat may play a major homeostatic role in the integration of nociception with other brain functions.

Adjuvants, Immunologic↗

PubMed2001

Projection sites of superficial and deep spinal dorsal horn cells in the nucleus tractus solitarii of the rat.

By using anterograde transport of biotin dextran amine injected into the cervical spinal dorsal horn, we have shown that fibres from superficial and deep dorsal horn project to the nucleus tractus solitarii via two distinct pathways. Afferent fibres from the superficial lamina (I-III) were found to course in the dorsal funiculus and terminate bilaterally in the caudal zone of the nucleus tractus solitarii (NTS), mainly within the commissural subnucleus. In contrast, afferents from the deeper dorsal horn laminae (IV-V) were found to course in the dorsolateral fasciculus and terminate ipsilaterally, mostly in the lateral areas of the caudal nucleus tractus solitarii. Similar, but more extensive patterns of labelled fibres were produced by injections into the white matter of the dorsal funiculus and dorsolateral fasciculus, respectively. These observations suggest that the caudal NTS not only serves as a location of visceral afferent convergence and integration, but may also be a receptive area for monosynaptic projections from dorsal horn neurons receiving sensory afferent inputs. Such projections may represent pathways through which NTS neurons are influenced by nociceptive and non-nociceptive information from the dorsal horn and thereby can co-ordinate the appropriate autonomic response, including adjustments in cardiorespiratory reflex output.

Afferent Pathways↗

PubMed2001

The paired homeodomain protein DRG11 is required for the projection of cutaneous sensory afferent fibers to the dorsal spinal cord.

Cutaneous sensory neurons that detect noxious stimuli project to the dorsal horn of the spinal cord, while those innervating muscle stretch receptors project to the ventral horn. DRG11, a paired homeodomain transcription factor, is expressed in both the developing dorsal horn and in sensory neurons, but not in the ventral spinal cord. Mouse embryos deficient in DRG11 display abnormalities in the spatio-temporal patterning of cutaneous sensory afferent fiber projections to the dorsal, but not the ventral spinal cord, as well as defects in dorsal horn morphogenesis. These early developmental abnormalities lead, in adults, to significantly attenuated sensitivity to noxious stimuli. In contrast, locomotion and sensori-motor functions appear normal. Drg11 is thus required for the formation of spatio-temporally appropriate projections from nociceptive sensory neurons to their central targets in the dorsal horn of the spinal cord.

Afferent Pathways↗

PubMed2001

Immunohistochemical profiles of spinal lamina I neurones retrogradely labelled from the nucleus tractus solitarii in rat suggest excitatory projections.

Three morphologically distinct types of lamina I neurones, fusiform, flattened and pyramidal, project from the spinal cord to the caudal part of the nucleus tractus solitarii in the rat, and may represent a pathway whereby peripheral stimuli can modify autonomic functions. The neurochemistry of these three types of projection neurones was investigated using retrograde neuronal tracing with cholera toxin B-subunit combined with dual and triple immunofluorescence labelling for different neuroactive substances. None of the lamina I neurones with immunoreactivity for GABA or glycine were found to project to the nucleus tractus solitarii, whereas high levels of glutamate immunoreactivity, which may indicate a glutamatergic phenotype, were found in 18.4% of fusiform, 9.6% of pyramidal and 2.1% of flattened projection neurones. Immunoreactivity for calbindin-D28K was present in 34.9% of fusiform cells, 18.3% of pyramidal cells and 10.5% of flattened cells, and nitric oxide synthase immunoreactivity was detected in 13.8% of fusiform cells, 1.1% of pyramidal cells and 4.2% of flattened cells that had projections to the nucleus tractus solitarii. Calbindin immunoreactivity was co-localised in major subpopulations of projection neurones of each morphological type that contained glutamate immunoreactivity, whereas co-localisation of nitric oxide synthase immunoreactivity in these neurones was relatively uncommon. The pyramidal cell was the only retrogradely labelled cell type found to be immunoreactive for substance P, but few (<5%) of these neurones were immunolabelled. These data are consistent with the hypothesis that lamina I neurones projecting to the dorsal vagal complex are not inhibitory, and that some of them, belonging mostly to the fusiform and pyramidal types, may exert excitatory, glutamate- or substance P-mediated effects upon inhibitory interneurones in the nucleus tractus solitarii. Such excitatory pathways could be involved in the attenuation of the reflex control of blood pressure by both painful and innocuous peripheral stimuli, such as those arising in injury and exercise.

Afferent Pathways↗

PubMed2001

Neurochemistry of superficial spinal neurones projecting to nucleus of the solitary tract that express c-fos on chemical somatic and visceral nociceptive input in the rat.

We have investigated the presence of three neurochemical markers, glutamate, calbindin-D28k, and nitric oxide synthase, in spinal neurones that transmit chemical noxious inputs from both the skin and the viscera, by combining retrograde labelling with the fluorescent tracer Fluorogold with dual labelling immunohistochemistry. Neurones projecting to the nucleus of the solitary tract (NTS) that expressed Fos protein in response to cutaneous or visceral noxious stimulation were concentrated in lamina I of the cervical and lumbosacral segments, respectively. Although both labelled neuronal populations were numerous, the spino-solitary cells that transmit visceral nociceptive input predominated over those transmitting cutaneous nociceptive input. Calbindin-D28k-immunoreactivity was observed in neurones of three morphological types (fusiform, flattened, and pyramidal) projecting to the NTS that were activated by somatic or visceral nociceptive neurones. Nitric oxide synthase and glutamate immunoreactivities were present only in viscerally activated nociceptive neurones projecting to the NTS. Glutamate-immunopositive NTS-projecting cells were exclusively of the flattened type, and the nitric oxide synthase-immunolabelled NTS-projecting cells comprised 75%/fusiform cells and 25% flattened cells. These data suggest that the involvement of excitatory spinal lamina I projection neurones in the transmission of peripheral chemical nociceptive inputs to the NTS may be restricted to information of visceral origin.

Afferent Pathways↗

PubMed2000

Spinomedullary pathways in the pigeon (Columba livia): differential involvement of lamina I cells.

The lamina I (marginal zone) of the spinal cord dorsal horn is an important site for pain processing. In mammals, lamina I neurons have been shown to constitute a heterogeneous population made up of four morphological groups with particular neurochemical nature, supraspinal connection patterns, and nociceptive response properties. In order to obtain a comparative view of the mechanisms of nociceptive processing, the analysis of the structural morphology and supraspinal connectivity of lamina I neurons was, in this study, extended to the avian family. Cholera toxin subunit B (CTb) was injected in the nucleus tractus solitarius (NTS), nucleus centralis medullae pars dorsalis (Cnd), and the dorsolateral portion of the nucleus reticularis lateralis (RLlat) of the pigeon (Columba livia), areas equivalent to the rat caudal medulla oblongata lamina I targets, which have been shown to receive differential projections from all cell groups present in lamina I of mammals. In the pigeon, lamina I cells project to the three medullary regions and present the same morphology of spinomedullary lamina I cells of mammals: the spinal-NTS and the spinal-RLlat pathways originated from fusiform, pyramidal, and flattened neurons, and the spinal-Cnd pathway from multipolar, pyramidal, and flattened neurons. Furthermore, the relative participation of each lamina I cell type in each pathway was found to be similar to that previously observed in the rat. The observed similarities on the anatomical organization of lamina I neurons in mammalian and avian species can be taken as a phylogenetic indication of the importance of the nociceptive circuitry centered in lamina I.

Animals↗

PubMed2000

Reciprocal connections between the medullary dorsal reticular nucleus and the spinal dorsal horn in the rat.

The synaptic architecture of spinal afferents of the dorsal portion (DRtd) of the medullary dorsal reticular nucleus (DRt) is studied. After iontophoretic injections of cholera toxin subunit B (CTb) into the superficial (laminae I-II), deep (laminae IV-V) or entire (laminae I-V) dorso-ventral extent of the spinal dorsal horn at the cervico-thoracic or lumbo-sacral levels, axonal boutons of two distinct types were labelled in the DRtd. Type A boutons (82% after cervico-thoracic injections and 92% after lumbo-sacral injections) were roundish, small and presented few mitochondria and small, round synaptic vesicles. Type B boutons (18% after cervico-thoracic injections and 8% after lumbo-sacral injections) were elongated, two to three times larger, and exhibited numerous mitochondria and larger round vesicles. Both types of bouton established asymmetrical synaptic contacts with small dendritic profiles and, less frequently, with dendritic trunks and perikarya. Retrograde labelling occurred in the postsynaptic profile of 15-18% type A boutons labelled from any injection site. Taken together with previous data on DRt-spinal synaptic contacts at the superficial dorsal horn, the present results point to the occurrence of a reciprocal excitatory loop connecting the dorsal DRt and lamina I, which may be at the basis of the DRt-mediated pain-facilitating effects described recently.

Afferent Pathways↗

PubMed1999

Structural characterization of marginal (lamina I) spinal cord neurons in the cat: a Golgi study.

The neuronal population of the spinal cord lamina I (marginal zone) was structurally characterized, in the cat, by the use of the Golgi method complemented by multivariate analysis of morphometric data. Four cell types were identified, two of them including two subtypes. Fusiform cells accounted for 43% of impregnated cells and presented flame-shaped rostrocaudally elongated perikarya and bipolar, either strictly longitudinal (fusiform A; 37%) or longitudinal and ventral (fusiform B; 6%) dendritic arbors with numerous short-pedicled spines. Fusiform cells preferentially occupied the lateral one-third of lamina I. Multipolar cells (22%) had ovoid perikarya with bulging surfaces and numerous primary dendritic trunks. Two subtypes could be distinguished: multipolar A cells (12%) with highly ramified dendrites covered with variably shaped spines and multipolar B cells (10%) with looser and less spiny dendritic arbors expanded for longer distances. Multipolar cells were more commonly found in the medial half of lamina I. Flattened cells (16%) possessed discoid perikarya flattened across the dorsoventral axis and aspiny, scarcely ramified dendritic arbors distributed horizontally within lamina I. They predominated in the intermediate one-third of the lamina. Pyramidal cells had triangular prismatic perikarya partially encased in the white matter overlying lamina I. They represented 19% of the impregnated neurons and were located along the entire lateromedial extent of the lamina. Each neuronal type included a few cells with perikarya and dendritic arbors three times larger than the rest. These so-called giant cells amounted to 6% of the entire lamina I neuronal population. According to the present data, the neuronal population of the spinal cord lamina I of the cat strongly resembles that of the rat (Lima and Coimbra, J. Comp. Neurol. 244:53-71, 1986), which strengthens the functional relevance of this structural classification.

Animals↗

PubMed1999

The medullary dorsal reticular nucleus facilitates pain behaviour induced by formalin in the rat.

The influence of the dorsal reticular nucleus (DRt) on pain behaviour during the formalin test was studied in the rat by lesioning the nucleus through local application of electrical current or quinolinic acid. Animals in which the DRt was lesioned ipsilaterally to the paw injected with formalin spent less time in focused (licking, biting or scratching the injected paw) and total (focused pain behaviour plus protection of the injected paw during movements) pain behaviour, and showed paw-jerks less frequently than non-lesioned animals in both phases 1 and 2 of the test. Animals in which the DRt was lesioned contralaterally to the injected paw presented a decrease in total pain behaviour and number of paw-jerks only during phase 2. The number of superficial (laminae I-II) and deep (laminae III-VI) spinal dorsal horn cells expressing the c-fos proto-oncogene 2 h after subcutaneous injection of formalin was reduced by 34% and 50%, respectively, in animals with an ipsilateral DRt lesion as compared to non-lesioned rats. No differences in c-fos expression were observed after lesioning the DRt contralateral to the formalin injection. The results indicate that the DRt is involved in the facilitation of nociception during the formalin test by enhancing the response capacity of dorsal horn neurons to noxious stimulation. It is suggested that the pronociceptive action of the DRt is mediated by the reciprocal connections it establishes with the spinal dorsal horn.

Animals↗

PubMed1998

Anatomical basis for the dynamic processing of nociceptive input.

The involvement of the lamina I, or marginal zone, of the spinal cord dorsal horn in pain processing has been extensively demonstrated. Its neuronal population comprises four structurally distinct neuronal groups, which were shown to be present in species as different as the rat, cat and pigeon. In the rat, each neuronal type presents a particular neurochemical nature and supraspinal projection pattern. In addition, there is recent evidence that supraspinal modulatory actions may affect differentially cells of different types. By combining retrograde tracing with noxious-evoked induction of the c fos proto-oncogene, it was verified that activation of different neuronal groups varies as a function of the brain site they target and the nature of the stimulus. These data suggest that the responsiveness of lamina I neurones is under controlling mechanisms which reflect the stimulus characteristics. Accordingly, both the spinal GABAergic and opioidergic anti-nociceptive actions appear to differ when different kinds df input are being processed. Moreover, supraspinal pain-modulatory circuits are also likely to control the excitability of each cell group. Not only reciprocal connections between the spinal cord and various pain-control centres have been identified, but also a correlation between the number of cfos positive projecting cells and the pain-inhibitory or facilitating role of their target has been observed. It is proposed that the compound nature of the nociceptive system serves a dynamic interplay between the spinal cord and the brain, which, by controlling the activation of distinct projection neurones, modulates the nociceptive signal while integrating nociceptive processing with several brain functions.

Journal Article↗

PubMed1997

Lesions of the caudal ventrolateral medulla block the hypertension-induced inhibition of noxious-evoked c-fos expression in the rat spinal cord.

The effect of lesioning the lateral portion of the caudal ventrolateral medullary reticular formation (VLMIat) on the noxious-evoked expression of the c-fos proto-oncogene in spinal neurons, was studied in short-term hypertensive rats. Occlusion of the renal artery for 96 h in unlesioned animals induced a 52% increase in blood pressure (BP) and a 66% decrease in the number of Fos-immunoreactive (Fos-IR) spinal cells following noxious cutaneous stimulation, as compared to values in normotensive controls. Lesioning the VLMIat in hypertensive rats by unilateral quinolinic acid (QA) injection (0.3 microl of a 180 nmol/microl solution) 24 h before noxious stimulation, prevented the Fos-IR cell decrease. In normotensive rats, lesioning the VLMIat produced no changes in c-fos expression. To investigate the role played by the VLMIat in cardiovascular control, BP and heart rate (HR) were measured during local injections of QA or glutamate (0.5 microl of a 100 nmol/microl solution) to normotensive animals. Injections of QA produced an immediate rise in BP and HR which reached maximal values (18 and 14% increase, respectively) 5 min after the administration onset, then returning gradually to baseline levels. Glutamate injections resulted in an immediate decrease of the same values, which reached 29 and 39%, respectively, 4 min after the beginning of injection, after which they decreased to baseline levels. These results suggest that VLMIat neurons inhibit nociceptive spinal neurons in response to rises in blood pressure, while exerting negative control of cardiovascular parameters. It is suggested that the VLMIat is involved in the genesis of hypoalgesia during hypertension.

Journal Article↗