Systemic changes following carrageenan-induced paw inflammation in rats.

OBJECTIVE AND DESIGN: Carrageenan-induced paw edema has been described as a local and acute inflammatory process. In fact, little is known about the time course and systemic changes following a carrageenan injection. In this study, we examine the systemic changes that follow carrageenan injection in the paw. METHODS: Acute inflammation was produced by subplantar injection of carrageenan in a hind paw of Sprague-Dawley rats. Saline was used in control rats. Paw volume was measured with a plethysmometer. The hot plate latency test was used to quantify antinociception. C-reactive protein (CRP) levels were measured with a sandwich enzyme immunoassay. Fibrinogen concentration was measured using the gravimetric method. Lung morphometric analysis was performed using an image processing package. Lungs and paws were also examined for tissue factor (TF) and proinflammatory cytokines expression by immunohistochemistry. RESULTS: We found diverse systemic changes including increased levels of acute phase proteins, such as CRP and fibrinogen, and a lung inflammatory process characterized by lung edema, fibrin deposition, and leukocyte infiltration. An elevated expression of TF, IL-6, IL-1ß, and TNFα, was observed in paw and lung tissue sections by immunohistochemical methods. CONCLUSION: This study provides new evidence that a local carrageenan injection induces a systemic response.

Antinociceptive effect of systemically administered dipyrone (metamizol), magnesium chloride or both in a murine model of cancer.

BACKGROUND: Opioid effectiveness to treat cancer pain is often compromised by the development of tolerance and the occurrence of undesirable side effects, particularly during long-term treatment. Hence, the search for more efficient analgesics remains a necessity. The main goal of this study was to relieve neuropathic symptoms associated with tumour growth by administering the non-opioid analgesic dipyrone (DIP) alone or in combination with magnesium chloride (MgCl2 ), an adjuvant that blocks the NMDA receptor channel. METHODS: Mice were inoculated with a melanoma cell line (B16-BL6) in the left thigh and two protocols were used to evaluate the effect of DIP (270 mg/kg), MgCl2 (200 mg/kg), or the combination DIP-MgCl2 . In the therapeutic protocol the drugs, alone or combined, were administered once tumour had promoted increased nociception. In the preventive protocol, drugs were administered prior to the appearance of the primary tumour. Tumour growth was assessed with a caliper and nociception was determined using behavioural tests. RESULTS: DIP promoted antinociception only at the beginning of both protocols due to the development of tolerance. The combination DIP-MgCl2 improved the antinociceptive effect, avoiding tolerance and reducing tumour growth in the preventive treatment, more efficiently than each compound alone. CONCLUSIONS: These results suggest that DIP-MgCl2 may represent a safe, affordable and accessible option to reduce tumour growth and to treat cancer pain avoiding the risk of tolerance, without the typical complications of opioids agents, particularly when long-term treatment is required. SIGNIFICANCE: This study shows a non-opioid analgesic combined with an adjuvant as a therapeutic option to treat cancer pain. The avoidance of antinociceptive tolerance when repeated administration is required, as well as tumor growth reduction, are additional advantages to be considered.

Prostaglandins and cyclooxygenases [correction of cycloxygenases] in the spinal cord.

The spinal cord is one of the sites where non-steroidal anti-inflammatory drugs (NSAIDs) act to produce analgesia and antinociception. Expression of cyclooxygenase(COX)-1 and COX-2 in the spinal cord and primary afferents suggests that NSAIDs act here by inhibiting the synthesis of prostaglandins (PGs). Basal release of PGD(2), PGE(2), PGF(2alpha) and PGI(2) occurs in the spinal cord and dorsal root ganglia. Prostaglandins then bind to G-protein-coupled receptors located in intrinsic spinal neurons (receptor types DP and EP2) and primary afferent neurons (EP1, EP3, EP4 and IP). Acute and chronic peripheral inflammation, interleukins and spinal cord injury increase the expression of COX-2 and release of PGE(2) and PGI(2). By activating the cAMP and protein kinase A pathway, PGs enhance tetrodotoxin-resistant sodium currents, inhibit voltage-dependent potassium currents and increase voltage-dependent calcium inflow in nociceptive afferents. This decreases firing threshold, increases firing rate and induces release of excitatory amino acids, substance P, calcitonin gene-related peptide (CGRP) and nitric oxide. Conversely, glutamate, substance P and CGRP increase PG release. Prostaglandins also facilitate membrane currents and release of substance P and CGRP induced by low pH, bradykinin and capsaicin. All this should enhance elicitation and synaptic transfer of pain signals in the spinal cord. Direct administration of PGs to the spinal cord causes hyperalgesia and allodynia, and some studies have shown an association between induction of COX-2, increased PG release and enhanced nociception. NSAIDs diminish both basal and enhanced PG release in the spinal cord. Correspondingly, spinal application of NSAIDs generally diminishes neuronal and behavioral responses to acute nociceptive stimulation, and always attenuates behavioral responses to persistent nociception. Spinal application of specific COX-2 inhibitors sometimes diminishes behavioral responses to persistent nociception.

Spinal prostaglandins are involved in the development but not the maintenance of inflammation-induced spinal hyperexcitability.

Prostaglandins (PGs) are local mediators of several functions in the CNS. Both primary afferent neurons and intrinsic cells in the spinal cord produce PGs, with a marked upregulation during peripheral inflammation. Therefore, the significance of spinal PGs in the neuronal processing of mechanosensory information was herein investigated. In anesthetized rats, the discharges of spinal nociceptive neurons with input from the knee joint were extracellularly recorded. Topical administration of prostaglandin E(2) (PGE(2)) to the spinal cord facilitated the discharges and expanded the receptive field of dorsal horn neurons to innocuous and noxious pressure applied to the knee joint, the ankle, and the paw, thus mimicking inflammation-induced central sensitization. Conversely, topical administration of the PG synthesis inhibitor indomethacin to the spinal cord before and during development of knee joint inflammation attenuated the generation of inflammation-induced spinal neuronal hyperexcitability. However, after development of inflammation, the responses of spinal neurons to mechanical stimuli were only reduced by systemic indomethacin but not by indomethacin applied to the spinal cord. Thus, spinal PG synthesis is important for the induction and initial expression but not for the maintenance of spinal cord hyperexcitability. Spinal PGE(2) application facilitated dorsal horn neuronal firing elicited by ionophoretic delivery of NMDA, suggesting that an interaction of PGs and NMDA receptors may contribute to inflammation-induced central sensitization. However, after development of inflammation, spinal indomethacin failed to reduce responses to ionophoretic delivery of NMDA or AMPA, suggesting that such an interaction is not required for the maintenance of central sensitization.

The projection from the lateral geniculate nucleus onto the visual cortex in the cat. A quantitative study with horseradish-peroxidase.

Horseradish-peroxidase (HRP) was injected (9-18 microng in 0.03-0.06 micronl) into cortical areas 17, 18 or 19 of 11 adult cats. After survival times of 17 hours to 7 days, the thalamus was examined for retrogradely HRP labelled nerve cells in serial transverse sections. From these sections, the percentage of labelled cells occurring in each subdivision of the dorsal lateral geniculate nucleus (LGNd) was calculated for each animal. One case each for injections in areas 17, 18, and 19 was then chosen for nerve cell size measurements in each LGNd subdivision. The perikaryal area of each labelled cell (N=689), and of representative samples of unlabelled cells (N=1137), was measured by planimetry. Size distribution histograms, mean values, standard deviation, and statistical significance levels were obtained by computer. It was found that area 17 receives a projection almost exclusively from laminae A and Al, and that the projecting cells belong to all cell size classes. Area 18 receives a projection mainly from laminae C and Al, and from the medial interlaminar nucleus (MIN). The projecting cells belong mainly to the large cell size classes. Area 19 receives a projection largely from MIN, and also from the C-laminae and extrageniculate cell groups. The projecting cells belong to all cell size classes, with some emphasis on the large cells of lamina C. A significant projection was found to exist from the parvocellular laminae of LGNd onto area 19 and, to a lesser degree, area 18. In conclusion, as one goes from area 17 and 18 and to 19 the projection source shifts from the A-lamine through the C-laminae on to MIN and extrageniculate cell groups. The cells which project to area 18 are on the whole larger than those which project to areas 17 and 19. A significant proportion of the contralateral visual input to area 18 is relayed via lamina C. These results provide a quantitative confirmation and extension of previous anatomical findings, and are in close relationship with physiological results regarding parallel channel processing in the visual system.

Cytoarchitecture and ultrastructure of nucleus prethalamicus, with special reference to degenerating afferents from optic tectum and telencephalon, in a teleost (Holocentrus ascensionis).

Histological structure and neuronal geometry of the nucleus prethalamicus of holocentrid teleosts, which is homologous to the nucleus rotundus of reptiles and birds and to the nucleus lateralis posterior-pulvinar complex of mammals, were studied by means of the Bodian, Nissl, toluidine blue, and Golgi methods. Synaptic terminals were classified electron microscopically, and terminal types originating from the telencephalon and the optic tectum were determined by electron microscopy in degeneration experiments. The nucleus prethalamicus is composed of four layers, in the following order from medial to lateral: a small-cell layer, a plexiform layer, a large-cell layer, and a marginal layer. Six types of terminals (U, L, Sp, Sd, F, and P) were distinguished in the nucleus, and the distribution pattern for each type of terminal was determined by counting its relative number in each layer. Sp terminals make synaptic contacts with small-cell dendrites or somata in the small-cell layer, and degenerate after telencephalic ablations. Sd terminals synapse exclusively with spines of large-cell dendrites in both marginal and large-cell layers, and degenerate after tectal ablations. Because only large neurons have been labeled after HRP injections into the telencephalon (Ito et al., '80, '82; Ebbesson, '80; Murakami et al., '83), it is considered that these neurons relay visual information from the optic tectum onto the telencephalon. It is hypothesized that the small neurons in the nucleus, which receive telencephalic input, might modulate the large neurons' relay function.

Cytoarchitecture of the tectum mesencephali in two types of siluroid teleosts.

The cytoarchitecture of the tectum mesencephali in the siluroid teleosts Bagrus and Ictalurus was studied by means of the Golgi method. These animals are known to have a restricted visual system and it seemed important to study whether this fact would affect the existence or the shape of the main neuron types which have been described for highly visual teleosts. It had been shown for a variety of teleosts that the retinotectal axons and terminals occupy almost exclusively the stratum opticum and the stratum fibrosum et griseum superficiale. The thickness of these strata in Bagrus and Ictalurus was found to be reduced. However, the main types of especially the vertically oriented neurons, such as the pyramidal, fusiform, large pyriform and periventricular neurons which have been described for highly visual species of teleosts, were also found in Bagrus and Ictalurus. Although their shape was somewhat distorted, these neurons, nevertheless, showed processes distributed to the same tectal layers as in highly visual teleosts and are accessible to horizontally distributed fiber systems such as marginal, telencephalotectal and commissural tectal fibers, as well as the retinotectal fibers. Nonvisual inputs appear to be considerably involved in the maintenance of the main neuron types in the siluroid tectum. For example, the pyramidal neuron's apical dendritic tree, which receives the excitatory input from the marginal fibers, is as well developed in siluroids as in highly visual teleosts.

Telencephalic projections in two teleost species.

The efferent pathways of the telencephalon were investigated in the percomorph Eugerres and the berycomorph Holocentrus. One telencephalic hemisphere was resected by suction and the animals were perfused 7-35 days thereafter. The brains were processed according to a modification (Method 7 in Ebbesson, '70) of the Fink-Heimer ('67) technique for selective silver impregnation of degenerating axons and terminals. Some fibers emerging from the lesioned telencephalic hemisphere terminate upon the contralateral hemisphere. The large bulk of efferent fibers, however, descends into the ipsilateral diencephalon and gives off the so-called strio-tectal bundle (STB) as well as the medial forebrain bundle (MFB). The remaining contingent eventually splits into the so-called strio-lobar bundle (SLB) and the lateral forebrain (LFB), but, previous to splitting, it contributes most of the telencephalic projection to the optic tectum in Eugerres, and gives abundant terminals to the ipsilateral nucleus rotundus or prethalamicus in both Eugerres and Holocentrus. The STB conveys all telencephalo-tectal fibers in Holocentrus, and some of them in Eugerres. Telencephalic efferents teminate ipsilaterally in the middle level of the tectum's stratum griseum centrale; in Holocentrus there is also a small projection to the stratum opticum. The MFB terminates at the caudal hypothalamus and gives terminals all along its course. The LFB also gives terminals all along its course and terminates upon a nucleus located between the midline and the corpus glomerulosum. The SLB spreads out and terminates in the inferior lobe of the hypothalamus.

Projections of the optic tectum in two teleost species.

The efferent pathways of the optic tectum have been investigated in the percomorph Eugerres and the berycomorph Holocentrus. A portion of the dorsal-dorsolateral region of the optic tectum was unilaterally resected by suction. The animals were perfused 6-30 days thereafter, and the brains were processed according to a modification (Method 7 in Ebbesson, '70) of the Fink-Heimer ('67) technique for the selective silver impregnation of degenerating axons and terminals. Three groups of fibers emerge from the lesioned region (a) a medial group, which runs towards the midline and terminates in the ipsilateral torus longitudinalis and the contralateral tectum; (b) an ascending group, which enters the dorsocaudal region of the diencephalon and terminates in pretectal cell groups, in the dorsomedial optic thalamic nucleus, and in the nucleus rotundus or prethalamicus; and (c) a descending group, which funnels down into the midbrain tegmentum. Here abundant terminals are given to dorsolateral cell groups and to the nucleus isthmi. A recurrent fascicle leaves the mainstream and ascends to terminate in scattered diencephalic cell groups, in the nucleus geniculatus posterior pars ventralis, and in the nucleus rotundus or prethalamicus. The bulk of descending fibers then forms an ipsilateral bundle, which gives terminals to the lateral reticular formation of mesencephalon and rhombencephalon, and a contralateral (i.e., the predorsal) bundle, which terminates in the medial reticular formation of mesencephalon and rhombencephalon.

Diameters and terminal patterns of retinofugal axons in their target areas: an HRP study in two teleosts (Sebastiscus and Navodon).

Studies in various vertebrate classes, particularly amphibians and mammals, have revealed that retinal ganglion cells with different functional properties project by means of axons of correspondingly different diameters onto specific target regions. Whether a similar pattern exists in teleosts is partly investigated in the present study. HRP was injected into the optic nerve of Sebastiscus and Navodon. The calibers of intraretinal HRP-labeled axons were classed as fine (ca. 0.8 micron), medium (ca. 1.3 micron), and coarse (ca. 2.5 microns). The calibers of HRP-labeled retinofugal axons were then determined in their target areas, and these can be summarized as follows: Optic hypothalamus: fine, medium. Lateral geniculate nucleus: fine. Dorsolateral thalamic nucleus: fine, medium. Area pretectalis: fine. Nucleus of the posterior commissure: fine, medium. Area ventralis lateralis, contralateral: fine, medium, coarse; ipsilateral: coarse. Optic tectum, stratum opticum: fine, medium; stratum fibrosum et griseum superficiale: fine, medium, coarse, segregated in sublayers; stratum album centrale: fine, medium, coarse. Therefore, fine fibers were found to reach all target areas except the ipsilateral area ventralis lateralis, and these were the only fibers found in the lateral geniculate nucleus, area pretectalis, and stratum griseum centrale of the optic tectum. Coarse fibers, on the other hand, were found only in the area ventralis lateralis and the optic tectum (stratum fibrosum et griseum superficiale and stratum album centrale). Terminal patterns of these fibers were also studied. Most fine fibers take tortuous courses giving off a few branches and terminate with many varicosities, and medium and coarse fibers give off several finer branches and terminate with bulbous swellings. The physiological significance of these findings is discussed. In addition, retrogradely labeled (retinopetal) cells were found in the olfactory bulb and the area ventralis pars ventralis of the telencephalon, as well as in the preoptic area and the dorsolateral thalamic nucleus.

Cytoarchitecture of the optic tectum of the squirrelfish, Holocentrus.

The Holocentrus has large eyes and a well-developed optic tectum. Nissl and fibers stains and various Golgi techniques show that the optic tectum of Holocentrus has six strata which can be subdivided into 14 alternating cell and fiber layers, some of which have additional organization. The stratum marginale (SM) is especially impressive in this fish and contains dendrites of pyramidal neurons, marginal fibers from torus longitudinalis, and axon-like processes (the SM ascending axons) from cells located in the stratum griseum centrale (SGC). Stratum opticum (SO) and stratum fibrosum et griseum superficiale (SFGS) have many small neurons with limited dendritic fields. The large, so-called pyramidal cell of SFGS has an extensive dendritic tree in SM and descending dendrites and axon to SGC. The latter has a variety of neurons with large dendritic fields in various layers of the tectum; the most distinctive, however, is the large fusiform neuron with its shepherd's crook axon. This stratum also has a dense layer of neuropil, the internal plexiform layer. Stratum album centrale (SAC) is primarily a fibrous layer, and stratum periventriculare (SPV) is a dense cellular area with the upper portion containing neuronal types also found in SGC and different from the typical neurons found in SPV. The latter have a major ascending branch with various dendritic patterns, and often do not have an identifiable axon; however, some of these cells have extensive branches throughout SFGS with an axon-like appearance. Some general conclusions were made about the functional significance of the various tectal layers and cell types.

Effects of antagonists to high-threshold calcium channels upon spinal mechanisms of pain, hyperalgesia and allodynia.

High-threshold voltage-dependent calcium channels enable calcium ions to enter neurons upon depolarization and thereby influence synaptic mediator/receptor systems, membrane excitability levels, second and third messenger concentration, and gene expression. These phenomena underlie several processes including those of normal nociception and of hyperalgesia and allodynia. The present article deals with the role of spinal L-, N- and P/Q-type calcium channels in short-lasting nociception as well as in the hyperalgesia and allodynia elicited by chemical irritants of peripheral nociceptors, inflammatory and mechanical lesions of peripheral tissues, and lesions of peripheral nerves. The studies summarized herein are based on the spinal delivery of specific antagonists to high-threshold calcium channels, and reveal that blockade of L-type, P/Q-type and, particularly, N-type channels can prevent, attenuate, or both, subjective pain as well as primary and/or secondary hyperalgesia and allodynia in a variety of experimental and clinical conditions.

Tolerance to repeated microinjection of morphine into the periaqueductal gray is associated with changes in the behavior of off- and on-cells in the rostral ventromedial medulla of rats.

Although the administration of opioids is the most effective treatment for pain, their efficacy is limited by the development of tolerance. The midbrain periaqueductal gray matter (PAG) participates in opioid analgesia and tolerance. Microinjection of morphine into PAG produces antinociception, probably through neurons in the rostral ventromedial medulla (RVM), namely through the activation of off-cells, which inhibit nociception, and the inhibition of on-cells, which facilitate nociception. After its repeated microinjection into the PAG morphine loses effectiveness. The present study sought to determine whether tolerance to PAG morphine administration is associated with changes in the behavior of RVM neurons. Morphine (0.5 microg/0.4 microl) or saline (0.4 microl) was microinjected into the ventrolateral PAG twice daily. Initially morphine caused a latency increase in the hot plate test (antinociception) but this effect disappeared by day 3 (tolerance). On day 4, each rat was anesthetized with halothane and recordings were made from off- and on-cells in the RVM, i.e. from neurons that decrease or increase their firing, respectively, just before a heat-elicited tail flick. In contrast to saline-pretreated rats, PAG microinjection of morphine in tolerant animals did not change the baseline activity of off- or on-cells, did not prevent the off-cell pause or the on-cell activation upon tail heating, and did not lengthen the tail flick latency. However, microinjection of kainic acid into the PAG (1) caused off-cells to become continuously active and on-cells to become silent, and (2) prevented the tail flick, i.e. exactly what morphine did before tolerance developed. These results demonstrate a correspondence between neuronal and behavioral measures of tolerance to PAG opioid administration, and suggest that tolerance is mediated by a change in opioid-sensitive neurons within the PAG.

Visual (optokinetic), somesthetic and vestibular inputs to the frog cerebellum.

Unitary response to visual (optokinetic), somesthetic (neck and limb) and vestibular stimulation were recorded from the Purkinje cell layer throughout most of the dorsal surface of the frog cerebellum. Simple spike activity in Purkinje cells and activity from cells without complex spikes were considered. Optokinetic responses (types I-III) were restricted to the dorsal rim and auricular lobes. Units were sensitive to very small velocity of optokinetic cylinder rotation (0.02-0.03 degrees/s) with peak sensitivity at about 1 degree/s. On the average an approximately linear relation of response amplitude to stimulus velocity was observed from 0.02 to 1 degree/s. The response progressively diminished above 1 degree/s to become very small at 30 degrees/s. Asymmetric response and silencing of firing during part of the cycle were nonlinearities observed with sinusoidal optokinetic stimulation in the range of 0.02-1 Hz, +/- 5-10 degrees (peak velocities 0.8-30 degrees/s). Somesthetic responses were recorded throughout most of the corpus cerebelli proper but the strongest input was to rostral regions. No somatotopic arrangement was found. Rather, convergence from more than one limb and neck was relatively common. Adaptation to successive cycles of stimulation was characteristic of somesthetic responses. Vestibular responses (type I-IV) were recorded throughout most of the explored area but the strongest input was to the dorsal rim and auricular lobes. From the analysis of unitary activity, the dorsal rim and auricular lobes are shown to be functionally linked to the vestibular and optokinetic systems whereas the explored part of the corpus is linked to the somesthetic and vestibular systems.

Visual (optokinetic) and somesthetic inputs to the cerebellum of bilaterally labyrinthectomized frogs.

Unitary responses to visual (optokinetic) and somesthetic (cutaneous and propioceptive ) stimulation were recorded from the Purkinje cell layer of the cerebellum of acute (up to 30 h) and chronic (30-90 days) bilaterially labyrinthectomized frogs. Simple spikes from Purkinje cells as well as activity from cells without complex spikes were considered in this paper. The properties of the response and the distribution (restricted to the dorsal rim and auricular lobes) of the units sensitive to optokinetic stimulation of labyrinthectomized frogs, both acute and chronic, were similar to those previously reported for normal animals. The properties of the responses to somesthetic neck and limb stimulation remained similar to those of normal animals. However, there was an increase in the number of units responsive to somesthetic stimulation within the dorsal half of the corpus cerebelli (including the dorsal rim), a region experimentally deprived of vestibular afferents, neck responsive units were 33% of the total in acutely and 61% in chronically labyrinthectomized animals (compared to 5% in normal). Limb responsive units were 49% in acute and 65% in chronic animals (compared to 12% in normal). A consequence of the increase in somesthetic input was convergence of optokinetic and somesthetic inputs at the level of single units within the dorsal rim, totally absent before the lesion. The results suggest that the somesthetic spinal input might substitute for at least some features of the vestibular input to the cerebellum in bilaterally labyrinthectomized frogs.

Differential effects of calcitonin gene-related peptide and calcitonin gene-related peptide 8-37 upon responses to N-methyl-D-aspartate or (R, S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate in spinal nociceptive neurons with knee joint input in the rat.

Calcitonin gene-related peptide is involved in the spinal processing of nociceptive input from the knee joint and in the generation and maintenance of joint inflammation-evoked hyperexcitability of spinal cord neurons. The present study examined whether this peptide influences the excitation of nociceptive spinal cord neurons by agonists at the N-methyl-D-aspartate and the non-N-methyl-D-aspartate [(R, S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate] receptors, both of which are essential for the excitation and hyperexcitability of spinal cord neurons. In anaesthetized rats extracellular recordings were made from dorsal horn neurons with knee input, and compounds were administered ionophoretically close to the neurons recorded. When calcitonin gene-related peptide was administered the responses of the neurons to the application of both N-methyl-D-aspartate and AMPA were increased. The coadministration of the antagonist calcitonin gene-related peptide 8-37 had no effect on the responses to N-methyl-D-aspartate, but it prevented the enhancement of the responses to N-methyl-D-aspartate by calcitonin gene-related peptide. By contrast, the administration of calcitonin gene-related peptide 8-37 enhanced the responses of the neurons to AMPA, and it did not antagonize but rather increased the effects of calcitonin gene-related peptide on these responses. The data suggest that the facilitatory role of calcitonin gene-related peptide on the development and maintenance of inflammation-evoked hyperexcitability is caused at least in part by the modulation of the activation of the dorsal horn neurons through their N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors. The different effects of calcitonin gene-related peptide 8-37 on the respones to N-methyl-D-aspartate and AMPA suggest that different intracellular pathways may facilitate the activation of N-methyl-D-aspartate and ionotropic non-N-methyl-D-aspartate receptors.

Visual receptive thalamopetal neurons in the optic tectum of teleosts (Holocentridae).

Tectal neurons previously known to receive retinofugal input were herein shown to project to the nucleus prethalamicus. Following HRP injections into the nucleus prethalamicus, pyriform neurons in the stratum periventriculare and stratum album centrale, and fusiform neurons in the stratum griseum centrale, were retrogradely labeled. Because the labeled types of neurons have been characterized as the main visual receptive neurons of the optic tectum, and because the nucleus prethalamicus of teleosts projects to the telencephalon, this nucleus can now be considered homologous to the nucleus rotundus of reptiles and birds and to the nucleus lateralis posterior-pulvinar complex of mammals, that is, it provides a relay for retinotectal visual input to the telencephalon. Orthogradely labeled terminals as well as retrogradely labeled neurons were also found in the dorsal area of the telencephalon. The tecto-prethalamotelencephalic projections are only ipsilateral.

The antinociceptive effect of PAG-microinjected dipyrone in rats is mediated by endogenous opioids of the rostral ventromedical medulla.

Microinjection of non-opioid analgesics, such as dipyrone (DIP), into the periaqueductal gray matter (PAG) in rats causes an inhibition of nociceptive circuits in the spinal cord. We have herein investigated whether this effect is mediated by opioidergic mechanisms in the rostral ventromedial medulla (RVM), which is an important relay between the PAG and the spinal cord. The responses of spinal wide-dynamic-range neurons to noxious stimulation of their receptive field (RF) were inhibited by microinjection of DIP (100 microg/0.5 microl) into PAG. Subsequent microinjection of naloxone (NAL; 0.5 microg/0.5 microl) into RVM reversed this inhibition. The present and previous results suggest that non-opioid analgesics, as well as opiates, inhibit nociception by activating descending opioidergic mechanisms in PAG and RVM.

Antinociception induced by PAG-microinjected dipyrone (metamizol) in rats: involvement of spinal endogenous opioids.

Dipyrone microinjection into the periaqueductal gray matter (PAG) elicits antinociception in rats by activating endogenous opioidergic circuits in PAG and the rostral ventromedial medulla. We have now found that endogenous opioids in the spinal cord are also involved. Responses of dorsal spinal neurons to noxious stimulation of a hindpaw were diminished (to 38-44%) by dipyrone microinjection (100 microg/0.5 microl) into the PAG. This was abolished by application of naloxone (50 microg/50 microl) to the spinal cord. The fact that dipyrone, a non-opioid analgesic, activates opioidergic circuits may be clinically important.

Morphological aspects of the teleostean visual system: a review.

This review is concerned with results of research carried out in the last two decades regarding visual pathways and centers in teleosts. It covers neither morphology of the retina nor development and plasticity. The optic nerve is considered in terms of axonal composition and retinotopic organization. The connections to the retina and from the retina are subsequently reviewed, and a general scheme is proposed for the retinofugal targets in thalamus and pretectum. The tectum opticum is then reviewed as regards its afferent connections from retina, telencephalon, diencephalon, mesencephalon and brainstem, with details on distribution of terminals, cell types contacted and synaptic structure. The efferent tectal connections are reviewed next, including their plausible cells of origin. Finally, a general diagram of the teleostean visual system is presented, and several circuits within this diagram are emphasized and discussed.