The role of peripheral vasopressin 1A and oxytocin receptors on the subcutaneous vasopressin antinociceptive effects.

BACKGROUND: Vasopressin (AVP) seems to play a role as an antinociceptive neurohormone, but little is known about the peripheral site of action of its antinociceptive effects. Moreover, AVP can produce motor impairment that could be confused with behavioural antinociception. Finally, it is not clear which receptor is involved in the peripheral antinociceptive AVP effects. METHODS: In anaesthetized rats with end-tidal CO2 monitoring, extracellular unitary recordings were performed, measuring the evoked activity mediated by Aß-, Aδ-, C-fibres and post-discharge. Behavioural nociception and motor impairment were evaluated under subcutaneous AVP (0.1-10 µg) using formalin and rotarod tests. Selective antagonists to vasopressin (V1A R) or oxytocin receptors (OTR) were used. Additionally, vasopressin and oxytocin receptors were explored immunohistochemically in skin tissues. RESULTS: Subcutaneous AVP (1 and 10 µg/paw) induced antinociception and a transitory reduction of the end-tidal CO2 . The neuronal activity associated with Aδ- and C-fibre activation was diminished, but no effect was observed on Aß-fibres. AVP also reduced paw flinches in the formalin test and a transitory locomotor impairment was also found. The AVP-induced antinociception was blocked by the selective antagonist to V1A R (SR49059) or OTR (L368,899). Immunohistochemical evidence of skin VP and OT receptors is given. CONCLUSIONS: Subcutaneous AVP produces antinociception and behavioural analgesia. Both V1a and OTR participate in those effects. Our findings suggest that antinociception could be produced in a local manner using a novel vasopressin receptor located in cutaneous sensorial fibres. Additionally, subcutaneous AVP also produces important systemic effects such as respiratory and locomotor impairment. SIGNIFICANCE: Our findings support that AVP produces peripheral antinociception and behavioural analgesia in a local manner; nevertheless, systemic effects are also presented. Additionally, this is the first detailed electrophysiological analysis of AVP antinociceptive action after subcutaneous administration. The results are reasonably explained by the demonstration of V1A R and OTR in cutaneous fibres.

Axons of Individual Dorsal Horn Neurons Bifurcated to Project in Both the Anterolateral and the Postsynaptic Dorsal Column Systems.

Sensory information stimulates receptors of somatosensory system neurons generating a signal that codifies the characteristics of peripheral stimulation. This information reaches the spinal cord and is relayed to supra-spinal structures through two main systems: the postsynaptic dorsal column-medial lemniscal (DC-ML) and the anterolateral (AL) systems. From the classical point of view, the DC-ML has an ipsilateral ascending pathway to the Gracilis (GRA) or Cuneate (CUN) nuclei and the AL has a contralateral ascending pathway to the ventral posterolateral (VPL) thalamic nucleus. These two systems have been the subject of multiple studies that established their independence and interactions. To analyze the ascending projections of L1-L5 spinal dorsal horn neurons in the rat, two retrograde neuronal tracers were injected into the GRA and the VPL. Additionally, an electrophysiological study was performed by applying electrical stimulation at the GRA or VPL and recording antidromic evoked activity in single unit spinal cord cells. Importantly, a subset of spinal dorsal horn neurons exhibited double staining, indicating that these neurons projected to both the GRA and the VPL. These double-stained neurons were located on both sides of the dorsal horn of the spinal cord. The spinal dorsal horn neurons exhibited antidromic and collision activities in response to both GRA and VPL electrical activation. These results show spinal cord neurons with bifurcated bilateral projections to both the DC-ML and AL systems. Based on these results, we named these neurons bilateral and bifurcated cells.

Prolactin fractions from lactating rats elicit effects upon sensory spinal cord cells of male rats.

Recently it has been suggested that the neurohormone prolactin (PRL) could act on the afferent nociceptive neurons. Indeed, PRL sensitizes transient receptor potential vanilloid 1 (TRPV1) channels present in nociceptive C-fibers and consequently reduces the pain threshold in a model of inflammatory pain. Accordingly, high plasma PRL levels in non-lactating females have been associated with several painful conditions (e.g. migraine). Paradoxically, an increase of PRL secretion during lactation induced a reduction in pain sensitivity. This difference could be attributed to the fact that PRL secreted from the adenopituitary (AP) is transformed into several molecular variants by the suckling stimulation. In order to test this hypothesis, the present study set out to investigate whether PRL from AP of suckled (S) or non-suckled (NS) lactating rats affects the activity of the male Wistar wide dynamic range (WDR) neurons. The WDR neurons are located in the dorsal horn of the spinal cord and receive input from the first-order neurons (Ab-, Ad- and C-fibers). Spinal administration of prolactin variant from NS rats (NS-PRL) or prolactin variant from S rats (S-PRL) had no effect on the neuronal activity of non-nociceptive Ab-fibers. However, the activities of nociceptive Ad-fibers and C-fibers were: (i) increased by NS-PRL and (ii) diminished by S-PRL. Either NS-PRL or S-PRL enhanced the post-discharge activity. Taken together, these results suggest that PRL from S or NS lactating rats could either facilitate or depress the nociceptive responses of spinal dorsal horn cells, depending on the physiological state of the rats.

Spinal LTP induced by sciatic nerve electrical stimulation enhances posterior triangular thalamic nociceptive responses.

Long-term potentiation (LTP) can be induced by electrical stimulation and gives rise to an increase in synaptic strength at the first relay. This phenomenon has been associated with learning and memory and also could be the origin of several pathological states elicited by an initial strong painful stimulus, such as some forms of neuropathic pain. We used high-frequency electrical stimulation of the sciatic nerve in anesthetized rats to produce spinal LTP. To evaluate the effect of spinal LTP on the activity of neurons in the posterior triangular nucleus of the thalamus (PoT), we applied an electrical stimulation (40 stimuli; 1ms; 0.5Hz; 1.5mA) to cutaneous tissues at 10-min intervals during at least 3h. In the majority of cases, PoT cells did not respond to cutaneous stimulation before LTP, but 50min after LTP induction PoT cells progressively began responding to the cutaneous stimulation. Furthermore, after 3h of LTP induction, PoT neurons could respond to cutaneous stimulation applied to different paws. Interestingly, the conduction velocities for the receptive field responses from the paw to the PoT cells were compatible with those of Aδ-fibers. Since PoT cells project to the insular cortex, the progressive increase in PoT activity and also the progressive unmasking of somatic receptive fields in response to LTP, place these cells in a key position to detect pain stimuli following central sensitization.

Identification of oxytocin receptor in the dorsal horn and nociceptive dorsal root ganglion neurons.

Oxytocin (OT) secreted by the hypothalamo-spinal projection exerts antinociceptive effects in the dorsal horn. Electrophysiological evidence indicates that OT could exert these effects by activating OT receptors (OTR) directly on dorsal horn neurons and/or primary nociceptive afferents in the dorsal root ganglia (DRG). However, little is known about the identity of the dorsal horn and DRG neurons that express the OTR. In the dorsal horn, we found that the OTR is expressed principally in neurons cell bodies. However, neither spino-thalamic dorsal horn neurons projecting to the contralateral thalamic ventral posterolateral nucleus (VPL) and posterior nuclear group (Po) nor GABaergic dorsal horn neurons express the OTR. The OTR is not expressed in skin nociceptive terminals or in dorsal horn nociceptive fibers. In the DRG, however, the OTR is expressed predominantly in non-peptidergic C-fiber cell bodies, but not in peptidergic or mechanoreceptor afferents or in skin nociceptive terminals. Our results suggest that the antinociceptive effects of OT are mediated by direct activation of dorsal horn neurons and peripheral actions on nociceptive, non-peptidergic C-afferents in the DRG.

Functional interactions between the paraventricular hypothalamic nucleus and raphe magnus. A comparative study of an integrated homeostatic analgesic mechanism.

This work compares the effects of electrical stimulation of the paraventricular hypothalamic nucleus (PVN) and the raphe magnus nucleus (RMg) on the single-unit response from dorsal spinal cord neurons activated by nociceptive receptive field stimulation. We evaluated the effects of stimulating the PVN or RMg individually or simultaneously, as well as PVN stimulation after RMg electrolytic lesion. PVN or RMg stimulation suppressed the A-delta, C fiber, and postdischarge, and we demonstrated that their simultaneous stimulation increases the duration and intensity of suppressive effects. RMg lesion increased the peripheral responses, but PVN stimulation continued to be suppressive. The intrathecal administration of 20 µl of a 10⁻5 M solution of a specific oxytocin antagonist strongly reduced the PVN effects, and 20 µl of 10⁻6 M naloxone significantly reduced the RMg suppression of receptive field responses. Some spinal cord cells presented a short-latency, evoked action potential (6.8 ms and a variability of ±0.5 ms) produced by the RMg stimulation. This is interpreted as a direct postsynaptic action of the RMg on the spinal cord cells. We never found similar responses produced by the PVN, and therefore, we propose that the PVN effects are presynaptic. Finally, the immunohistochemical experiments confirmed the oxytocinergic and the vasopresinergic innervation used by the PVN projection to the RMg, and they raise the possibility that other neurotransmitters are involved. We conclude that the PVN and the RMg form part of a homeostatic analgesic mechanism acting on the same spinal cord cells to block the noxious information, but using different mechanisms. Both structures, and others, contribute to the homeostatic mechanism of endogenous analgesia.

Sexually dimorphic expression of oxytocin binding sites in forebrain and spinal cord of the rat.

The central actions of oxytocin on reproduction-related functions and behaviors are strongly steroid-dependent and gender specific. This study characterizes sexual differences in the oxytocin binding site expression in forebrain and spinal cord of the rat. Using film autoradiography, we quantified the density of oxytocin binding sites in the ventromedial hypothalamic nucleus, the medial and central nuclei of the amygdala, the medial bed nucleus of the stria terminalis and the spinal cord dorsal horns both in adult male and female rats, and during development. In addition, neonatal castrated males and intact neonatal females treated with a single injection of testosterone (1 mg) were examined. Data showed a sexual dimorphism in the expression of oxytocin binding sites in the spinal cord dorsal horns and in restricted areas of the forebrain that are sensitive to gonadal steroids such as the ventromedial hypothalamic nucleus, but not in gonadal steroid insensitive sites such as the central nucleus of the amygdala. Adult males had higher oxytocin binding site densities in the ventromedial hypothalamic nucleus and dorsal horns than females. In the forebrain, but not in the dorsal horn, this sexual difference required a perinatal exposure to testosterone. Neonatal castration only abolished the sexual difference in the ventromedial hypothalamic nucleus of adults, but not in the dorsal horn. Furthermore, females that received a single injection of testosterone 1 day after birth showed significant increases in the density of oxytocin binding sites in the ventromedial hypothalamic nucleus, medial nucleus of the amygdala and medial bed nucleus of the stria terminalis. In addition, the findings suggest that the sexual difference in the ventromedial hypothalamic nucleus also requires gonadal hormones in adulthood. Our data support the hypothesis that sexually dimorphic oxytocin binding sites may contribute to the regulatory central actions of oxytocin in gender specific functions and behaviors such as nociception and reproduction.

Different wheat germ agglutinin-horseradish peroxidase labeling in structures related to the development of amygdaline kindling in the rat.

The anterior commissure, medial and lateral bed nuclei of the stria terminalis and both sides of the medial prefrontal cortex showed a progressive increasing of wheat germ agglutinin-horseradish peroxidase labeling (WGA-HRP) in successive stages of amygdaline kindling, after 48 h of a right amygdala WGA-HRP injection. In contrast, during the first stages the number of labeled cells in the contralateral amygdala was reduced, reaching control values after the first generalized seizure. The present paper indicates that these structures are involved in the propagation and generalization of the epileptic activity. Our findings show that both sides of the medial prefrontal cortex can be activated before the contralateral amygdaloid complex, during the development of the amygdaline electrical kindling in the rat.

Brain somatic representation of phantom and intact limb: a fMRI study case report.

Reports on phantom limb patients concerning neuronal reorganization using non-invasive methods have focused mainly on the cortical regions and suggest the presence of pain as the cause of this reorganization. The phantom limb, however, includes other somatic and motor sensations other than pain. Here we describe the results of non-painful stimulation in cortical and subcortical lateralization and reorganization and also examine the involvement of subcortical structures in phantom limb telescoping perception. We describe an enlarged contralateral cortical representation of the stump, a cortical and thalamic bilateral representation of the remaining leg, and a neuronal correlate of a telescoping perception of the phantom limb. The missing leg produces an enlarged cortical representation due to abnormal information and the remaining leg has a bilateral SII representation, which could be related to new, compensatory functions. The telescoping perception of a phantom limb by the stimulation of misallocation points was correlated with lenticular nuclei, thalamic and cingulate gyrus activation. We therefore propose that the reorganization concept of a phantom limb, applied mainly to the cortex, must extend to the thalamic and the somatosensory and motor systems (pathways and relay nuclei).

Effects of kindling in wheat germ agglutinin-horseradish peroxidase [corrected] labeling in neurons of the interamygdaloid pathway in rats.

This paper describes in kindled rats an increment in wheat germ agglutinin-horseradish peroxidase labeling in anterior commissure, bed nuclei of stria terminalis and amygdala. Three groups of animals were analyzed: control, sham-operated and kindled animals with ten convulsive generalized seizures. Results show that kindled animals have an increase in fiber labeling in anterior commissure and in the bed nuclei of stria terminalis, as well as a greater number of labeled neurons in amygdala. This label enhancement is related to the hyperexcitability of neurons produced by epilepsy, and could be associated to the propagation and formation of secondary foci and related plastic changes occurring during kindling.

Effects of cypermethrin on the electroencephalographic activity of the rat: a model of chemically induced seizures.

Cypermethrin is a potent representative member of the type II pyrethroid insecticides. This pyrethroid is used worldwide and has become a part of our environment. Until the present study, little information about its toxic effects in the central nervous system (CNS) was available. The aim of this study was, then, to determine the effects of repeated exposure to cypermethrin by means of assessing the electroencephalographic (EEG) activity in the rat. Cypermethrin was administered daily in a 300 mg/kg i.p. dose, below the LD50 value. After daily administration, the EEG activity was recorded and evaluated for 30 min. Paroxysmal epileptic activity appeared after the first and second days of cypermethrin administration. Frequency and numbers of bursts of epileptic activity also increased throughout the days of exposure to cypermethrin. Some of the paroxysmal events were present with behavioral anomalies, such as generalized tonic-clonic seizures. These effects are important because they could be related to the incidence of epileptic activity in humans chronically exposed to cypermethrin.

Perinatal administration of testosterone induces hypertrophy of the anterior commissure in adult male and female rats.

A possible sex difference in the mean sagittal area of the anterior commissure (AC) was investigated in normal, newborn-castrated, and perinatally-androgenized rats. A second experiment included castrated adult rats from each sex exposed to testosterone twelve days before sacrifice. In normal rats, as well as in those exposed to testosterone as adults, no quantitative difference was found in the AC. However, perinatal exposure to testosterone induced a 20-25% increase in the mean area of the AC of rats from each sex. It is proposed that gonadal sex steroids may have a reciprocal influence upon the structure of central olfactory pathways, due to the influences of the main olfactory system upon gonadotropin secretion.

Different direct pathways of locus coeruleus to medial prefrontal cortex and centrolateral thalamic nucleus: electrical stimulation effects on the evoked responses to nociceptive peripheral stimulation.

Projections from the locus coeruleus (LC) to the centrolateral thalamus (Cl) and the medial prefrontal cortex (PfCx) were studied using orthodromic and antidromic stimulation techniques. The LC is a major noradrenergic source in the central nervous system, and its descending projections provide an important source of pain suppression at spinal level. Previously, the author has described a cortico-thalamic loop involved in pain modulation. The present paper reports on a study of the participation of LC as part of an ascending pain-control system acting on the cortico-thalamic loop.Rats were anaesthetized with halothane, and single unit recordings were made in LC using glass micropipettes. Stainless steel electrodes were placed in cortex and thalamus for electrical stimulation.Stimulation in PfCx or Cl produces antidromic responses in neurons in LC. The latencies, conduction velocity and location of neurons in LC projecting to PfCx or Cl structures are described. Separate projections to both structures have significantly different conducting velocities, arriving earlier at Cl (mean conduction velocities 0.27 and standard deviation +/-0.06 m/s) and then at PfCx (mean conduction velocities 0.20+/- 0.04 m/s). The presence of orthodromic responses suggests reciprocal connections. The paper also describes the suppression of spontaneous and nociceptive-evoked activity in the PfCx and Cl following electrical stimulation in LC.It is proposed that the LC innervation could be associated with an ascending noradrenergic system acting upon a Cl-PfCx pain-modulation mechanism. Copyright 1998 European Federation of Chapters of the International Association for the Study of Pain.

NADPH-diaphorase-stained neurons after experimental epilepsy in rats.

The aim of this study was to determine the neuronal participation of nitric oxide (NO) in experimental epilepsy. To reach this objective, we established the amount of cells presenting nitric oxide synthase (NOS) and the amygdaline concentrations in the L-arginine-nitric oxide synthesis pathway. A group of fully epileptic rats, induced by the kindling procedure and that had reached at least 10 generalized seizures, was studied. We evaluated behavioral stages, electroencephalographic activities, and histochemical NOS-positive cells and carried out high-pressure liquid chromatography (HPLC) determinations of arginine, citrulline, and glutamic acid. Our results showed that behavioral and electrographic frequency, and duration of epileptic activities, were increased during the kindling process. Image processing system of NOS cells showed two types of intensities in cell stains in hippocampus, caudate-putamen, and amygdala. When we independently counted the two types of NOS stain cells, a selective increase in the number and density of weak-stained cells was observed, while dark-stained cells did not change in the studied structures. Additionally, arginine, citrulline, and glutamic acid concentrations in amygdala increased in kindled animals. The differential and specific increase in the stained cells expressing the nitric oxide synthase, as well as the increase in concentrations of the L-arginine-nitric oxide pathway in amygdala, suggested a relationship with the progressive augmentation in the electrophysiological hyperactivity characteristic of generalized epilepsy.

Cortical facilitatory action on centralis lateralis thalamic activity during the development of carrageenin-produced inflammation.

In order to understand the neuronal mechanisms involved in acute and chronic pain, we studied the thalamic and cortical control action, which allows the suppression of the neuronal responses to noxious stimulation. As an experimental pain model we used carrageenin injected in the paw of male Wistar rats. The tonic facilitatory cortical control on centralis lateralis thalamic nuclei (CL) activity is described at different times after carrageenin-produced inflammation. Simultaneous extracellular unit recordings were carried out at CL and medial prefrontal cortex (PCx) cells in anesthetized male Wistar rats. The PCx control was tested by blocking in a transient and reversible manner, using the cortical spreading depression (CSD). Carrageenin injection (1%; 0.2 ml) into the plantar surface of the right hind paw, and the influence of Lidocaine (2%; 0.2 ml) applied in the inflamed paw, was tested on unit activity in PCx and CL cells. Thalamic cells recorded in acute and subacute stages (24-72 h after carrageenin administration) were activated by tactile, light pressure and joint movement stimulation yielded before the injection. After carrageenin, the thalamic cells displayed spontaneous high frequency burst discharges, also presenting a progressive and significant increase (p < 0.001, ANOVA test) of their spontaneous firing rate when compared with control cell activity. Lidocaine reduced the enhanced activity induced by carrageenin in thalamic neurones (p < 0.001, Student t test). In PCx neurones were also recorded in acute and subacute stages. Cortical cells from acute and subacute group were activated by nociceptive and non-nociceptive stimulation. In acute stage, cortical cells increased their firing rate after carrageenin and we could not observe modifications upon their firing rate due to Lidocaine. The CSD blocked all cortical activity in acute and subacute stages. During the CSDs, overall thalamic activity was suppressed in neurones from acute (91%) and subacute (87%) stages. The blockage was observed when the propagated wave produced by CSD arrived into the medial prefrontal cortex. The CSD also suppressed the PCx and the CL noxious responses evoked by pressure in the receptive field. This study shows the tonic facilitatory control of the PCx upon intralaminar thalamic noxious responses, during acute and subacute stages of carrageenin produced-inflammation. In the literature, it has been proposed that the CL thalamic nuclei and the prefrontal cortex are involved in processing the affective component of pain. It may be possible to suppress the thalamic activity during chronic pain, using the transient and reversible blockage of CSD, giving rise to a reduction in the affective reactions to pain. This could also be a therapeutic alternative in chronic pain treatment.

Actions of sciatic nerve ligature on sexual behavior of sexually experienced and inexperienced male rats: effects of frontal pole decortication.

The action of the hyperalgesia produced by the loose ligature of the sciatic nerve on the sexual behavior of two groups of sexually experienced and inexperienced male rats was studied. The putative changes in the behavior induced by this manipulation were attempted to be counteracted by the removal of the anterior frontal cortex. Independently of the sexual experience, the ligature of the sciatic nerve did not modify any parameter of the sexual behavior, except for a slight prolongation of the intromission latency. Surprisingly, the removal of the cortical frontal pole resulted in drastic changes in the sexual behavior of sexually inexperienced male rats such as an increase in the intromission and ejaculation latencies and the postejaculatory interval. These changes were not observed in the sexually experienced group. Interestingly, the sciatic nerve ligature prevented the changes in the copulatory behavior produced by the frontal cortex removal. These results suggest that the hyperalgesia induced by the sciatic nerve ligature was unable to alter the sexual behavior. By contrast, the frontal cortex removal produced important changes in the sexual behavior that depend upon the previous sexual experience. All results are discussed on the bases of the neural control underlying the possible relationships between algesia and male sexual behavior.

Correlation between oxytocin neuronal sensitivity and oxytocin-binding sites in the amygdala of the rat: electrophysiological and histoautoradiographic study.

Central nucleus (Ce), basomedial and medial nuclei of the amygdala (AMG), and some parts of the striato-pallidal system, present high densities of oxytocin (OT)-binding sites. In order to examine whether these OT-binding sites are functional receptors, the OT neuronal sensitivity and the presence of OT-binding sites were investigated using electrophysiological and autoradiographical techniques. To identify the AMG cells, electrical stimulation of the oval subnucleus of the bed nucleus of the stria terminalis (Ov) and of the parabrachial nucleus (Pb) were performed. Somatic and auditory sensory stimulations were also tested. OT was applied by iontophoresis during extracellular single unit recordings of cells which were localized in frontal brain sections subsequently used for histoautoradiographic detection of OT-binding sites. Cells responding to Ov nucleus stimulation were located in the AMG, mainly in the Ce nucleus, whereas those responding to Pb nucleus stimulation were distributed in the Ce nucleus and in the postero lateral part of the caudate putamen. Iontophoretic OT application excited 45% of the recorded cells (43/96) among which OT alone activated spontaneous firing rate of 30 and potentiated the L-Glutamate (GLU)-induced activation on 13. These OT-sensitive neurons were located mainly in the AMG and caudate putamen areas containing OT-binding sites. These results strongly suggest that OT-binding sites found in the AMG are functional receptors upon which OT could act as a neurotransmitter and as a neuromodulator to regulate autonomic functions.

Further evidence for the involvement of SmI cortical neurons in nociception: their responsiveness at 24 hr after carrageenin-induced hyperalgesic inflammation in the rat.

In this electrophysiological study, the responsiveness of neurons in the primary somatosensory cortex (SmI) was analyzed in rats with carrageenin-induced hyperalgesia for 24 hr. The functional implication of some changes in neuronal activity was improved in a few cases by a pharmacological test with Xylocaine injection in or close to the neuronal receptive field (RF), or with systemic aspirin. Unit recordings were performed alternately in the SmI cortex contralateral (Cc) or ipsilateral (Ci) to the inflamed hindpaw. In 29 rats with hyperalgesia tested prior to the recording session, 218 cells (128 in the Cc, 90 in the Ci) were tested with mechanical stimuli. In each SmI cortex, about 50% of them were driven by the stimulus. The "nonresponsive" neurons exhibited a higher firing rate in the Cc than in the Ci. The "responsive" (i.e., the somatosensory) neurons were classified according to their response to light touch, pinch, or joint movement. There was a highly significant difference between the two cortices, essentially because of the high proportion of "joint" Cc neurons (27 of 73 [37%] of the somatosensory neurons in the Cc, vs. only 8 of 47 [17%] in the Ci). "Light touch" neurons (41 of 73 [56%] in the Cc, vs. 35 of 47 [74.5%] in the Ci) had small RFs contralateral to the recording site. Of the 41 Cc cells of this type, 23 did not exhibit the classical characteristics of "light touch" cells; in particular, they exhibited striking discharges triggered by the stimulus but outlasting the stimulus duration, or occurring without intentional stimulation. These abnormal discharges were depressed or suppressed by injection of a local anesthetic (Xylocaine) in or close to the neuronal RF. "Pinch" neurons were very rare (5 of 73 [7%] in the Cc, vs. 4 of 47 [8.5%] in the Ci). Responses elicited from the inflamed paw were more pronounced than those from the noninflamed paw. "Joint" neurons were more numerous in the Cc than in the Ci. In addition, their responses obtained from contralateral RFs, and therefore from the inflamed paw, were more sustained than Ci responses elicited from the noninflamed paw. Afterdischarges of Ce neuronal responses and spontaneous paroxysmal activity were common on this side and were depressed by local anesthetic (Xylocaine) in their RFs or by systemic aspirin. These electrophysiological data emphasize the implication of SmI cortex in inflammatory hyperalgesia and more generally in pain processing.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain Na+/K(+)-ATPase regulation by serotonin and norepinephrine in normal and kindled rats.

In this work we confirmed the activation of rat brain Na+/K(+)-ATPase by norepinephrine (NE) and observed a variable response of the enzyme according to the brain region considered. In isolated neuronal or glial fractions from normal cerebral cortices, we studied the response of the enzyme to increasing concentrations of serotonin (5-HT) (10(-9)-10(-3) M). A dose-dependent response over basal values was present in glial fractions, beginning at 10(-6) M. No such response was obtained in the neuronal fractions. In amygdaloid kindled brains, the pattern of activation by NE was different than in controls: less pronounced (cortex, brainstem, and diencephalon), inhibition-activation (cerebellum), or no change (striatum). The activation of Na+/K(+)-ATPase by 5-HT observed in the control glial fraction was not present in the kindled glial fraction. In conclusion, 5-HT seems to activate Na+/K(+)-ATPase preferentially in glial cells, and the kindling process markedly modifies this regulation. The normal response to NE in brain homogenates is less altered by kindling than is the response to 5-HT in the same regions.

Facilitating action of medial prefrontal cortex upon the noxious thermally-evoked responses in thalamic centralis lateralis nucleus.

This paper shows a medial prefrontal cortex (CxAP9) facilitating influence upon the unit activity of the centralis lateralis (Cl) nucleus of the thalamus, in rats anesthetized with urethane. Cortical influences were studied using both cortical cooling and cortical spreading depression (CSD) procedures. Both spontaneous and noxious thermally evoked activities were considered. When CSD was propagated and affected the CxAP9, as well as during the cooling of this area, both spontaneous activity and the responses evoked in Cl cells by noxious stimulation were blocked. This effect was interpreted as a cortical disfacilitation upon Cl cells. During the cortical silent period we tested the excitability of a few Cl cells, provoking their activation by passing electrical current across the same Cl recording electrode. No changes were observed in their excitable response threshold during CSD or cortical cooling. Our results are in agreement with the proposition of a tonic cortical facilitatory action upon the spontaneous and noxious-evoked responses recorded in the Cl cells.