UMLS:C0344307 - FACTA Search

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Query: UMLS:C0344307 (analgesia)
28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The analgesic effect of morphine was antagonized in mice by intracerebroventricular pretreatment with taurine, gamma-aminobutyric acid (GABA) or glycine and was potentiated by ethylene glycol tetra-acetic acid (EGTA) but not altered by L-glutamate or L-aspartate. The potentiation of morphine analgesia by EGTA was reversed by a concentration of taurine that did not alter the tail-flick response. The selective depletion of 45Ca2+ from synaptic vesicles observed with morphine administration was significantly inhibited by taurine injection (1.2 mumol/brain, i.vt.) but was not altered by the same dose of GABA. Inhibition of ATP-dependent 45Ca2+ uptake in synaptosomes by morphine was also completely reversed by taurine (10(-2)M which by itself did not alter 45Ca2+ uptake. These results suggest that antagonism of morphine analgesia by taurine may be caused by blockade of the morphine-induced inhibition of both ATP-dependent synaptosomal 45Ca2+ uptake and changes in synaptic vesicular 45Ca2+ localization, while the antagonism by GABA was not associated with synaptosomal Ca2+.
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PMID:Effects of amino acids, especially taurine and gamma-aminobutyric acid (GABA), on analgesia and calcium depletion induced by morphine in mice. 678 72

Stimulation in the nucleus raphe magnus produces analgesia in behavioral paradigms and inhibits spinal cord nociceptive neurons. Similar effects result from stimulation of the periaqueductal gray (PAG). Such actions may be mediated via a synaptic link between PAG and nucleus raphe magnus or the adjacent reticular formation. In this study we have examined the effects of biogenic amines applied iontophoretically in the vicinity of nucleus raphe magnus neurons that project to the spinal cord in monkeys. Raphe-spinal tract (RST) neurons were identified by antidromic activation after stimulation of the dorsolateral funiculi at an upper lumbar level. The actions of serotonin, quipazine, norepinephrine, dopamine and acetylcholine (ACh) were tested against the background activity, the activity evoked by glutamate pulses or the excitation of RST cells by stimulation in the PAG. Serotonin, quipazine, norepinephrine and dopamine produced a current-dependent inhibition of background activity and the responses to glutamate pulses in all RST cells tested. No cases of excitation were found. By contrast, ACh enhanced activity produced by glutamate pulses in all RST cells observed. ACh also enhanced the background activity of all but one of the RST cells; however, ACh did not activate cells with little or no background discharge. Serotonin and norepinephrine often inhibited PAG excitation of RST cells. No facilitation of PAG excitation was observed. We conclude that the actions of serotonergic and catecholaminergic agonists on raphe-spinal cells are inhibitory whereas the effect of ACh is facilitatory.
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PMID:Effects of biogenic amines on raphe-spinal tract cells. 686 25

These studies were designed to examine the role of the norepinephrine-containing cells comprising the nucleus locus coeruleus (LC) in the mediation of pain perception and morphine-induced antinociception. Nociceptive threshold and morphine-induced analgesia were measured following monosodium-L-glutamate lesions of the LC and adjacent tegmentum (nucleus parabrachialis ventralis; PBV) at 17, 24 and 31 days after surgery. Nociceptive thresholds assessed by the tail flick and hot plate assays were not altered following lesions which included both the LC and PBV (Group 1) or by lesions of the PBV (Group 2) alone. Examination of lesion-induced effects on the capacity of morphine to induce analgesia revealed that damage which included both LC and PBV as well as that confined primarily to the PBV resulted in attenuation of analgesia induced by morphine. Those lesions which involved the LC altered norepinephrine content in the cortex, spinal cord and medial brain stem; however, no correlation could be demonstrated between the attenuation of morphine-induced analgesia and the changes in norepinephrine content of the brain regions examined. Thus, destruction of the LC does not appear to be responsible for the decreased effectiveness of morphine. The only region consistently damaged in both groups 1 and 2 was the ventral parabrachial nucleus. Therefore, we tentatively conclude that destruction of the PBV was responsible for the observed attenuation of morphine analgesia.
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PMID:Effects of locus coeruleus lesions on morphine-induced antinociception. 737 Jul 62

Injection of 0.5 microliter L-sodium glutamate (60 mM) into the periaqueductal gray matter of the rat resulted in a short-lived analgesia as assessed by the tail-flick method. Naloxone (1 mg/kg) attenuated glutamate-induced analgesia when injected 30 min but not 5 min before testing. Paradoxically, a higher dose of naloxone (10 mg/kg) significantly potentiated glutamate analgesia when injected 5 min but not 30 min before testing. Moreover, this higher dose also potentiated analgesia when injected 5 min prior to 12 mM glutamate, a dose of glutamate previously found to be ineffective in causing analgesia. Microinjections of either 60 mM or 1 M KCl failed to elicit analgesia, indicating the specificity of the glutamate effect. Taken together with several other lines of evidence, the present findings suggest that glutamate-induced analgesia may be mediated by processes quite different from those underlying morphine analgesia. It is further suggested that a dose-related naloxone antagonism is not a necessary criterion for assessing endogenous opioid activity.
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PMID:Glutamate-induced analgesia: blockade and potentiation by naloxone. 737 1

These studies examined the role of bulbospinal serotonin-containing neurons found in the nucleus raphe magnus and nucleus raphe pallidus in the mediation of morphine-induced antinociception. Lesions were made using both electrolytic coagulation and the axon-sparing technique of monosodium-L-glutamate injection to ascertain whether the effects following lesions in the area of the medullary raphe nuclei are due to destruction of neuronal perikarya or fibers passing near these nuclei. These studies revealed that lesions of both the raphe magnus and raphe pallidus resulted in decreased nociceptive thresholds and attenuation of morphine-induced analgesia. Such effects were observed regardless of the lesioning method used, which suggests that destruction of neurons in these nuclei was responsible for lesion-induced effects. In addition, lesion-induced changes in spinal cord serotonin content and morphine analgesia were significantly correlated which lends support to the conclusion that the bulbospinal serotonin systems are necessary for the mediation of morphine effects. Furthermore, no correlation was observed between changes in spinal cord norepinephrine content and morphine analgesia. This observation suggests that lesion-induced damage to bulbospinal noradrenergic fibers which pass near the midline does not contribute to the attenuation of morphine analgesia resulting from raphe lesions.
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PMID:Effects of raphe magnus and raphe pallidus lesions on morphine-induced analgesia and spinal cord monoamines. 744 40

In the present investigation we have tested the hypothesis that spinal glutamate release by inflammatory stimuli causes hyperalgesia through sensitization of the primary sensory neurons associated with nociception. In these experiments, the rat paw hyperalgesia pressure test in which inflammatory hyperalgesia is blocked by the intraplantar administration of morphine (MPH) or SNAP, a NO donor was used. Glutamate and glutamatergic ionotropic agonists such as NMDA or AMPA injected intrathecally (i.t.) caused a dose-dependent hyperalgesia. Quisqualate or ACPD, both of which are glutamate metabotropic receptor agonists, had no hyperalgesic effect. The hyperalgesic response to glutamate and NMDA injected i.t. was antagonized by the intraplantar (i.pl.) injection of either MPH or SNAP. This observation indicates that the hyperalgesia induced by glutamate acting through an NMDA pre-synaptic receptor causes sensitization of the primary sensory neurons. Confirming that the analgesia by i.pl. injection of SNAP or MPH was due to an action in primary peripheral sensory neurons, it was shown that pretreatment of the paws with methylene blue (MB, an inhibitor of guanylate cyclase) or with MB and L-NMMA (an inhibitor of NO synthase) abolished their respective analgesic effect. AMPA i.t. induced hyperalgesia was not inhibited by either i.pl. administration of MPH or SNAP, indicating that its hyperalgesic capacity results from an action at a site other than the primary sensory neuron.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glutamate spinal retrograde sensitization of primary sensory neurons associated with nociception. 753 32

Several amino acids including aspartate, glutamate and glycine and the monoamine serotonin were retrieved from the extracellular space of the dorsal horn of the lumbar spinal cord in the alpha-chloralose anesthetized cat in vivo using a transverse microdialysis probe. Neurotransmitter concentrations were determined using high pressure liquid chromatography in combination with fluorescence (amino acid) or electrochemical (serotonin) detection. Intradermal injection of 3% capsaicin into the hindleg either ipsilateral or contralateral to the dialysis probe was used to evoke release. Extracellular concentrations of aspartate, glutamate and serotonin increased significantly following capsaicin injection into the ipsilateral limb. An almost equal increase in serotonin and a less pronounced, but still significant, increase in aspartate accompanied contralateral capsaicin injection. Glutamate concentrations increased in the dialysate during contralateral capsaicin injection in about half of the animals. These data are consistent with the hypothesis that Asp and Glu are both neurotransmitters released from nociceptive primary afferent fibers and/or interneurons activated by these fibers. In addition, Asp is presumed to be released from intrinsic spinal or descending systems following nociceptive stimulation. Bilateral release of 5HT into the dorsal horn most likely results from non-topographic activation of descending endogenous analgesia pathways.
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PMID:Amino acids and serotonin are released into the lumbar spinal cord of the anesthetized cat following intradermal capsaicin injections. 768 45

The present experiments were designed to study the effect of glutamate on cortical somatosensory area II (S II) producing descending modulation of intralaminar nuclei (ILN) via the motor cortex (MCtx) in acupuncture analgesia. The glutamate antagonist glutamate diethylester (GDEE) or saline was topically applied at MCtx in 17 cats. Single unit activities of ILN neurons were extracellularly recorded. The results were as follows: 1. The nociceptive responses of ILN neurons were attenuated by stimulating S II after topical administration of saline at MCtx. However, the inhibitory effect of stimulating S II in the same neurons was reduced after application of GDEE. There was a significant difference at 0'-1' after the stimulation between the two groups (n = 10, P < 0.05). 2. The inhibitory effect of electroacupuncture (EA) on nociceptive responses was reduced after topical application of GDEE, while marked inhibition was shown at 0'-10' after cessation of EA in the saline control group (n = 11, P < 0.05). The results, together with the finding that the majority of S II neurons could be activated by EA, showed that glutamate released from S II to MCtx might be involved in corticofugal modulation of ILN from S II via MCtx in acupuncture analgesia.
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PMID:[Involvement of glutamate in corticofugal modulation of intralaminar nuclei from SII via motor cortex in acupuncture analgesia]. 783 44

We have previously demonstrated that the nucleus raphe magnus (NRM) sends a predominantly inhibitory projection to the lateral reticular nucleus (LRN); however, the pharmacology of this pathway is not known. The purpose of this study was to examine the role of norepinephrine in the NRM-LRN system using both electrophysiological and behavioral techniques. Sixty-nine LRN cells were recorded extracellularly. Cells were tested for their response to noxious and innocuous peripheral stimulation applied to the dorsal body surface. The majority of cells were classified as wide dynamic range, with inhibition being the predominant response; receptive fields were located primarily on the tail and hind limbs. The effect of excitatory amino acid glutamate (GLU) administration into NRM (GLU-NRM) was tested on all 69 cells. GLU-NRM inhibited 55 of 69 LRN cells tested; 7 cells were excited and 7 cells did not respond. Thirty-nine LRN cells were tested for their response to norepinephrine (NE) iontophoretically applied in LRN (NE-LRN). Two distinct types of effects were noted. In 9 cells, both NE-LRN and GLU-NRM produced a strong inhibition, with the magnitude of effect between the 2 drugs significantly correlated. In a second group of cells (n = 12), GLU-NRM produced an inhibitory effect while NE-LRN had no effect on the cells' baseline firing rate. However, when the 2 drugs were applied simultaneously, NE-LRN blocked the inhibitory effects of NRM stimulation. The effect of the alpha 2-receptor antagonist yohimbine (YOH) on NRM-evoked responses was tested in 30 LRN cells. The majority of these cells were inhibited by GLU-NRM. Similar to the dichotomous effect noted by NE-LRN, YOH applied iontophoretically in LRN (YOH-LRN) had two predominant effects on NRM-produced inhibition. In 14 of 27 cells, YOH-LRN significantly potentiated the inhibitory effects of NRM stimulation by increasing the duration of the inhibitory epoch an average of 100 sec. In 7 of 27 cells, YOH directly applied in LRN partially antagonized NRM-evoked inhibition. In a second series of experiments, microinjection cannulas were placed within NRM and LRN in order to determine the effect of blocking alpha 2-receptor activity within LRN on NRM stimulation-produced analgesia in an intact animal. Administration of D,L-homocysteic acid in NRM resulted in a significant increase in baseline tail-flick latency of approximately 140%. Pretreatment with YOH (3 micrograms in 0.5 microliter) in LRN resulted in a significant potentiation of this analgesic effect.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of norepinephrine in the interaction between the lateral reticular nucleus and the nucleus raphe magnus: an electrophysiological and behavioral study. 830 8

Numerous studies have shown that the lateral reticular nucleus (LRN), located in the caudal ventrolateral medulla, is an important nuclear region in the descending analgesia system. Activation of this brainstem region, either electrically or chemically, results in a reduction in nociceptive threshold. In addition, destruction of LRN abolishes the tonic descending inhibition present on dorsal horn neurons. Recent neuroanatomical tracing studies have shown that the nucleus raphe magnus (NRM), long implicated in nociception, sends direct projections to LRN; however, no information exists regarding the physiological characteristics of this pathway, nor its role in the endogenous descending analgesia system. The purpose of this study was to physiologically characterize the synaptic influence(s) of projections from the NRM to the LRN using electrophysiological recording, electrical and chemical stimulation, and iontophoretic techniques. Sixty-one percent of LRN neurons responded to single pulse stimulation of NRM; 52% of the responsive cells were excited and 48% were inhibited. The mean latency to onset of excitation was 4.9 +/- 1.2 ms. High frequency (100 Hz) electrical stimulation of NRM influenced 69/102 neurons; 52% (36/69) were excited, while 48% (33/69) were inhibited. Microinjection of glutamate into NRM significantly modified the discharge of 83% (93/112) of LRN cells tested; of these, 71% were inhibited, while 29% were excited. In 35 cells the effects of the excitatory amino acid antagonist kynurenic acid (KYN) were studied. In 75% of the cells excited by glutamate administration into the NRM (18/24), KYN partially antagonized this response. In 11 LRN cells inhibited by NRM chemical stimulation, KYN had no effect on this inhibition. Overall, 95% of the LRN cells responsive to NRM stimulation were also responsive to noxious peripheral stimulation, indicating that these cells are receiving ascending information from the spinal cord regarding somatosensory stimulation as well as receiving descending input from the NRM. It is concluded that LRN neurons are highly responsive to both noxious peripheral stimulation and NRM efferent activation, and that this region plays a significant role as an integrator for both ascending and descending information.
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PMID:Electrophysiological characterization of the projection from the nucleus raphe magnus to the lateral reticular nucleus: possible role of an excitatory amino acid in synaptic activation. 846 5

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