Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Potent analgesia is elicited by electrical stimulation of the periaqueductal gray (PAG), dorsal raphe nucleus (DRN) and intralaminar thalamus. Horseradish peroxidase conjugated wheat germ agglutinin (HRP-WGA) was stereotaxically pressure injected into the parafascicular (PF) or central medial (CM) nucleus to identify brainstem afferents to the intralaminar thalamus. WGA-immunoreactive (-ir) neurons were identified in the DRN, PAG and lateral dorsal tegmentum (LDTg) after PF and CM injections. Many retrogradely labeled cells in the DRN and ventral PAG were also serotonin-ir, and a portion of WGA-ir cells in the LDTg were substance P-ir. These results substantiate previous studies implicating the intralaminar thalamus and periaqueductal region, as well as serotonin and substance P, in antinociception.
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PMID:Serotonin and substance P afferents to parafascicular and central medial nuclei. 132 Feb 63

The midbrain periaqueductal gray (PAG) participates in diverse functions such as analgesia, autonomic regulation, sexual behavior, and defense/escape responses. Anatomical studies of the circuits involved in such functions have largely focused on the connections of PAG with the medulla. Projections to PAG from forebrain structures are extensive, but their organization has received little attention. Previous anatomic studies indicate that the medial preoptic area (MPO), involved in a variety of physiological and behavioral functions, is a major source of afferent input to the periaqueductal gray. Here, we have examined the topography of reciprocal connections between these two structures in the rat by using wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) and Phaseolus vulgaris leucoagglutinin (PHA-L). Multiple WGA-HRP injections at several rostrocaudal levels of PAG retrogradely labeled large numbers of neurons in the medial preoptic area; labeled cells were primarily located in the medial preoptic nucleus, the median preoptic nucleus, and the region lateral to the medial preoptic nucleus. The distribution of labeled cells shifted medially to laterally along the rostral to caudal axis of the medial preoptic area. Rostrally, there was selective retrograde labeling in the central and lateral divisions of medial preoptic nucleus, whereas caudally, labeled cells were primarily located only in the lateral subdivision of medial preoptic nucleus. Tracer injections in PAG also produced strong anterograde labeling in MPO. WGA-HRP and PHA-L injections in the medial preoptic area resulted in dense anterograde labeling along the entire rostrocaudal axis of PAG. The terminal labeling in PAG from the medial preoptic area was not uniformly distributed throughout PAG, however. Instead, this projection formed one or two rostrocaudally oriented longitudinal columns that terminated in different subregions of PAG along the entire rostrocaudal axis of this structure. Rostrally, inputs from the medial preoptic area project heavily to dorsomedial PAG, and at mid-PAG levels, the projection becomes distinctly bipartite with two discrete longitudinal terminal columns in dorsomedial and lateral PAG; caudally, the heaviest labeling is in ventrolateral PAG. The projection also exhibited a central to peripheral (radial) gradient; labelled fibers and terminals were heaviest near the aqueduct and much lower in the peripheral parts of PAG. WGA-HRP injections in MPO also produced retrograde labeling of neurons at all rostrocaudal levels of PAG; more neurons were labeled in the rostral than the caudal half of PAG. The majority of labeled cells were located in dorsomedial and ventral/ventrolateral parts of PAG; only a few neurons in the dorsal raphe region appear to project to MPO.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Reciprocal connections between the medial preoptic area and the midbrain periaqueductal gray in rat: a WGA-HRP and PHA-L study. 137 79

Previous studies using a pharmacological approach suggested a neural pathway emanating from the periaqueductal gray (PAG) to the nucleus accumbens relevant to antinociception. This was investigated with neurochemical and histochemical methods in the present study. Push-pull perfusion and radioimmunoassay were used to measure the release of immunoreactive-(ir) enkephalin (ir-ENK) and ir-beta-endorphin (ir-beta-EP) in the nucleus accumbens after microinjection of morphine into the PAG and the nucleus raphe dorsalis (NRD) of the rabbit. Morphine administration elicited an increase in ir-ENK and ir-beta-EP in the nucleus accumbens. Horseradish peroxidase (HRP) retrograde tracing in combination with 5-hydroxytryptamine (5-HT) immunocytochemistry revealed a serotonergic projection from the NRD and ventral PAG to the nucleus accumbens in the rabbit. About 7% of the serotonin-positive cells in the NRD and ventral PAG send fibers directly to the nucleus accumbens, with an ipsilateral dominance. These results indicate the existence of a serotonergic pathway from the NRD to the N. accumbens involved in opioid analgesia.
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PMID:Neurochemical and morphological evidence of an antinociceptive neural pathway from nucleus raphe dorsalis to nucleus accumbens in the rabbit. 163 20

Conjugate of horseradish peroxidase and wheat germ agglutinin (HRP-WGA conjugate) was injected into the midbrain central gray (MCG) of three adult rats. Frontal sections of the diencephalon were first treated with diaminobenzidine and hydrogen peroxide to detect the retrogradely transported conjugate. They were then stained immunohistochemically to detect pro-opiomelanocortin (POMC)-derived peptides (ACTH, beta-endorphin and alpha-MSH). The coexistence of the three POMC-derived peptides was confirmed by the immunohistochemistry of three consecutive sections stained with antiserum specific to each peptide. Some of the neuronal perikarya distributed in and around the arcuate nucleus were positive to the immunohistochemical stain for POMC-derived peptides, and, concomitantly, were labeled with HRP-WGA conjugate, which indicated that they projected to the MCG. They were mostly concentrated in the rostral three-fifths of the arcuate nucleus. The finding that some of the POMC neurons in the arcuate nucleus project to the midbrain central gray deserves interest, because the central gray is involved in analgesia induced by opioid peptides.
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PMID:Projection of pro-opiomelanocortin neurons from the rat arcuate nucleus to the midbrain central gray as demonstrated by double staining with retrograde labeling and immunohistochemistry. 245 87

Afferent projections to the nucleus raphe magnus (NRM) and dorsal raphe nucleus (DRN) were identified using retrograde transport of horseradish peroxidase conjugated wheat germ agglutinin (HRP-WGA). Neurons were labeled in important nociceptive regions including periaqueductal gray (PAG), arcuate nucleus, lateral hypothalamus and medial thalamic nuclei following both injections. We have immunocytochemically identified opiocortin/WGA neurons in the arcuate nucleus following NRM and DRN injections. Dual stained catecholamine/WGA perikarya were found in zona incerta, locus coeruleus, substantia nigra, nucleus tractus solitarius and adjacent A2, C2 and C3, lateral paragigantocellular reticular nucleus/C1 and lateral reticular nucleus/A1 following DRN injections and in zona incerta, substantia nigra, nucleus tractus solitarius/A2 and lateral reticular nucleus/A1 after NRM injections. These results provide further evidence for opiocortin and catecholamine modulation of analgesia.
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PMID:Opiocortin and catecholamine projections to raphe nuclei. 260 53

The transplantation of peripheral neural tissue into the CNS has been shown to alter blood-brain barrier (BBB) permeability to intravascularly injected proteins such as horseradish peroxidase. The pharmacological consequences of such BBB alterations following the transplantation of adrenal medullary tissue, isolated bovine chromaffin cell suspensions, or PC12 cell suspensions into the pain modulatory regions of the periaqueductal gray (PAG) or subarachnoid space of the lumbar spinal cord were studied using agents that normally do or do not readily pass the BBB. The injection of nicotine in animals with adrenal medullary or chromaffin cell transplants produces potent analgesia, most likely due to the stimulated release of opioid peptides and catecholamines from the transplanted cells. This analgesia could be blocked by nicotinic antagonist mecamylamine, which normally passes the BBB, but not by nicotinic antagonist hexamethonium, which normally does not readily pass the BBB. Furthermore, quaternary nicotinic agonists tetramethylammonium and 1,1-dimethyl-phenyl-piperazinium had no effect on pain sensitivity in animals with adrenal medullary implants. The Met-enkephalin peptide analog, D-Ala-Met-enkephalinamide, which normally does not alter pain sensitivity when injected systemically due to limited penetration to the CNS, produced analgesia in animals with adrenal medullary, bovine chromaffin cell, and PC12 cell implants in the PAG, but not in control gelfoam-implanted animals. This analgesia, as well as analgesia induced by nicotine, was completely blocked by naloxone pretreatment, but not by naloxone methobromide, a quaternary derivative of naloxone that does not normally pass the BBB.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacologic consequences of the vascular permeability of chromaffin cell transplants in CNS pain modulatory regions. 290 75

Small volumes (5-40 nl) of an aqueous solution of wheat-germ-agglutinin-conjugated horseradish peroxidase (WGA-HRP) were injected unilaterally into midbrain structures of 18 adult, albino rats. In 17 of these preparations cells of many types were found to be retrogradely labeled in cervical and lumbar spinal cord segments. The data reported here concern the number and location of labeled cells from injection sites in the midbrain that affected two distinct cell populations: neurons within the marginal layer (lamina I cells) and neurons of the nucleus of the dorsolateral funiculus (NDLF cells). In ten of the preparations, only nine of which are reported in detail here, a total of 1,831 labeled lamina I cells were identified. In the lumbar enlargement they reached a density of more than 60 cells/mm. Of these, 85% projected to medial portions of the caudal, contralateral midbrain. Injection sites that were centered in the caudal periaqueductal gray (PAG) and/or in the immediately adjacent region of nucleus cuneiformis labeled the largest numbers of lamina I cells. Cells of the NDLF were retrogradely labeled in all preparations in which lamina I cells were labeled but they were also observed in five cases in which lamina I cells were not labeled. A total of 1,914 NDLF cells were labeled from all injection sites. These cells were found to have essentially a bilateral distribution with 57% of the cells located in the contralateral DLF. Although there is substantial overlap between the terminal fields of lamina I and NDLF cells within the midbrain, NDLF cells had a more diffuse target area encompassing the reticular core of the midbrain and PAG, bilaterally, while the target area for lamina I cells was comparatively discrete, being largely restricted to the more medially situated midbrain structures, contralaterally. Whether the terminations of lamina I cells in and near the PAG are from collaterals of spinothalamic neurons originating in lamina I, or a subclass of lamina I neurons that project exclusively to the midbrain, is not known. It is significant, however, that lamina I cells, known to be activated by noxious stimuli to the skin, should project to a region of the brain stem from which analgesia can be produced by electrical stimulation or by local application of opiates.
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PMID:Long ascending projections to the midbrain from cells of lamina I and nucleus of the dorsolateral funiculus of the rat spinal cord. 384 Jan 82

The distribution of corticotropin releasing factor (CRF)-immunoreactive structures in the rat thalamus was studied after treatment with high doses of colchicine (100 micrograms/100 g b.wt.) with peroxidase-antiperoxidase (PAP) immunocytochemistry in vibratome sections. CRF-immunopositive perikarya were found in the 'posteromedial complex' of the thalamus, including the ventromedial, paracentral, mediodorsal, rhomboid, parafascicular nuclei, centrum medianum and ventromedial portion of the posterolateral nucleus. In addition, CRF-containing perikarya were observed in the pretectal and subthalamic nuclei. CRF-immunoreactive processes were seen in most of the medial nuclei of the thalamus. The presence of CRF-immunopositive structures in the thalamus suggests that CRF not only functions as a hypophysiotropic hormone regulating the release of ACTH and beta-endorphin from the pituitary, but also as a neurotransmitter or neuromodulator, playing an important role in nociception and analgesia.
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PMID:Immunocytochemical localization of corticotropin releasing factor (CRF)-like immunoreactivity in the thalamus of the rat. 615 62

Both systemic and intrathecal capsaicin release and deplete substance P from primary sensory afferents and induce prolonged chemical and thermal analgesia. Given the existence of efferents containing substance P together with a pain-inhibitory serotoninergic pathway, the present study investigated the effects of intraventricular capsaicin upon basal nociception, analgesic responsivity to opiates and substance P immunoreactivity. Following treatment with capsaicin at doses of 25, 50 and 100 micrograms or with vehicle, alterations in basal rodent flinch-jump thresholds as well as analgesic responses to 5 and 2.5 mg/kg of morphine were measured over a post-injection time course. Tissues were then processed for immunocytochemistry for substance P according to the unlabelled antibody peroxidase antiperoxidase procedure. Decreases were noted in jump thresholds only at 72 h following capsaicin. Moreover, morphine analgesia at both doses was attenuated in dose-dependent fashion following capsaicin with the highest dose (100 micrograms) producing a significant decrease in analgesic efficacy. Substance P-like immunoreactivity in capsaicin-treated rats was not appreciably depleted compared with vehicle controls in the substantia gelatinosa of the spinal cord and V cranial nerve, the raphe magnus and periaqueductal gray, the medullary, pontine and mesencephalic reticular formation, the substantia nigra, the corpus striatum and the central nucleus of the amygdala. By contrast, substance P-like immunoreactivity appeared to increase in the medial nucleus of the amygdala. In the absence of depletion of substance P immunoreactivity by the intraventricular capsaicin, the observed alterations in opiate analgesic responses may possibly be due to alterations in other transmitters or peptide systems.
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PMID:Intraventricular capsaicin: alterations in analgesic responsivity without depletion of substance P. 617 20

The combined horseradish peroxidase retrograde transport-peroxidase-antiperoxidase immunohistochemical procedure was utilized in the present study to ascertain the sites of origin of serotonin and neurotensin projections to the rodent nucleus raphe magnus. The major serotonin inputs to the raphe magnus arise from the B-8 and B-9 groups of Dahlstrom and Fuxe (Dahlstrom, A., and K. Fuxe (1964) Acta Physiol. Scand. Suppl. 232 62: 1-55), the nucleus reticularis paragigantocellularis, and the nucleus reticularis gigantocellularis pars alpha. Neurotensinergic projections to the raphe magnus originate predominantly from the periaqueductal gray, the nucleus solitarius, the dorsal and ventral parabrachial nuclei, and the nucleus cuneiformis. The periaqueductal gray and the nucleus paragigantocellularis were found to provide both a neurotensin and a serotonin projection to this raphe nucleus. The present results indicate that several brain stem nuclei, which have been implicated previously in endogenous analgesia mechanisms, provide serotonergic and neurotensinergic input to the nucleus raphe magnus.
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PMID:The sites of origin brain stem neurotensin and serotonin projections to the rodent nucleus raphe magnus. 617 7


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