Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The synaptic relationships formed by medial lemniscal (ML) or spinothalamic tract (STT) axon terminals with neurons of the somatosensory ventroposterolateral thalamic nucleus of the macaque monkey have been examined quantitatively by electron microscopy. ML and STT axons were labeled by the anterograde axon transport of WGA-HRP following injection of the tracer into the contralateral dorsal column nuclei, or the dorsal horn of the spinal cord, respectively. Thalamic tissue was histochemically reacted for the presence of HRP. Serial thin sections were stained with a gold-labeled antibody to GABA, to determine which neuronal elements exhibited GABA immunoreactivity (GABA-ir). Serially sectioned thalamic structures were recorded in electron micrographs and reconstructed in three dimensions by computer. Individual ML axon terminals form multiple synaptic contacts with segments of the proximal dendritic trees of thalamocortical relay neurons and also synapse upon the dendritic appendages of GABA-ir interneurons (local circuit neurons). These GABA-ir dendritic appendages contain synaptic vesicles and are presynaptic (presynaptic dendrites) to the same segments of relay neuron dendrites that receive ML contacts. When analyzed in serial sections and reconstructed by computer, the ML terminals form triadic relationships (ML, GABA appendage, and relay neuron dendrite) or more complex glomerular arrangements involving multiple appendages, all of which then contact the relay neuron dendritic segment. In contrast, multiple STT terminals make synaptic contacts along segments of projection neuron dendrites and are usually the only type of profile to contact that segment of dendrite. More than 85% of the spinal afferents form simple axodendritic synapses with relay cells and do not contact GABA-ir appendages. The thalamic synaptic relationships of ML terminals are fundamentally different from those formed by the STT. Because STT neurons predominatly transmit information about noxious stimuli, the simple axodendritic circuitry of the majority of these spinal afferents suggests that the transmission of noxious information is probably not subject to GABAergic modulation by thalamic interneurons, in contrast to the GABAergic processing of non-noxious information carried by the ML afferents. The differences in the GABAergic circuits of the thalamus that mediate ML and STT afferent information are believed to underlie differential somatosensory processing in the forebrain. We suggest that changes in thalamic GABAergic dendritic appendages and GABA receptors following CNS injury may play a role in the genesis of some central pain states.
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PMID:Medial lemniscal and spinal projections to the macaque thalamus: an electron microscopic study of differing GABAergic circuitry serving thalamic somatosensory mechanisms. 751 7

Electric stimulation applied to the posterior surface of the spinal cord (SCS) is an established treatment in certain chronic pain syndromes resistant to conventional therapeutic procedures. Despite the clinical value of SCS, the mechanisms behind the efficacy of the method are largely unknown. Several neurotransmitters in the CNS (e.g. opioids, serotonin, noradrenaline, substance P, GABA), have been proposed to be involved in the pain-alleviating effect of SCS. However, as yet there is no evidence that these would be involved in the beneficial effects of SCS. We have studied neurotransmitter release, using microdialysis techniques, in the spinal dorsal horn and the periaqueductal grey substance (PAG) of the rat and the cat, induced by SCS applied with current parameters equivalent to those used clinically in man. Up to now dialysates have been assayed for GABA, serotonin and substance P with highly sensitive methods. Three groups of studies have been carried out: (1) dorsal horn microdialysis in rats under halothane anesthesia during acute SCS; (2) dorsal horn microdialysis in cats under barbiturate anesthesia or following decerebration, and (3) PAG microdialysis in awake, unrestrained rats with chronic SCS. In the dorsal horn studies, microdialysis probes of different sizes were implanted in the lower lumbar dorsal horns. In the PAG studies, rats had guide cannulas for microdialysis stereotactically inserted into the PAG. SCS was applied at a low thoracic level with 50 or 100 Hz; 0.2 ms and an intensity amounting to 2/3 of the motor threshold. The microdialysis probes were perfused with modified Ringer's solution. Fractions of the dialysate were collected at various intervals. GABA and serotonin were assayed by reverse-phase HPLC, while substance P was investigated using a highly sensitive radioimmunoassay. SCS induced a significant release of GABA in the dorsal horn, most marked in the fraction following the stimulation period. In the rats with PAG microdialysis, the GABA level decreased significantly following two stimulation periods, although transitional increases during SCS were noted in some animals. In the decerebrated cat, a significant release of serotonin in the dorsal horn was obtained with SCS, while the levels of the metabolite 5-HIAA were little influenced by stimulation. On the contrary, in the decerebrated preparation there was no release of substance P in the dorsal horn with SCS, although in the intact cat under barbiturate anesthesia a significant release was induced.4+ off
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PMID:Release of neurotransmitters in the CNS by spinal cord stimulation: survey of present state of knowledge and recent experimental studies. 753 60

Thanks largely to the study of the brainstem nuclei that mediate stimulation analgesia, the involvement of the monoamines in the descending control of pain is now well established. The periaqueductal grey, the raphe nuclei (NRM and DRN) and the locus coeruleus are all key brainstem sites for the control of nociceptive transmission in the spinal cord. Although the initial emphasis was on 5-HT as the transmitter mediating this control at spinal levels, it is clear from more recent work that NA has an equally important part to play. How (or even if) the two amines differ in their roles and actions in analgesia is, however, still an open question. The small size and complexity of the brainstem areas from which analgesia may be elicited by electrical stimulation complicates the interpretation of the data. Stimulating currents may spread to surrounding regions mediating opposite effects to that of the main region stimulated. Opiates and GABA are clearly involved in descending control at both brainstem and spinal levels, although the relative roles of the different types of amino-acid and opiate receptors is still hotly debated. Despite the fact that the first report on stimulation analgesia appeared more than a quarter of a century ago in 1969, the precise connections and cord synaptology are still the basis of ongoing research. It is perhaps ironic, in an issue dedicated to new molecules and mechanisms, that those transmitters most involved in descending inhibition should be such old and familiar friends.
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PMID:Descending control of pain. 757 56

Intrathecal (i.t.) administration of the gamma-aminobutyric acidB (GABAB) receptor antagonist CGP 35348 in the rat resulted in a dose-dependent pain-like response (vocalization) to innocuous mechanical stimuli and touch/pressure). The effect was maximally evoked by stimulation applied to a dermatome corresponding to the spinal levels of the i.t. injections. The paw withdrawal threshold to pressure was also moderately decreased after i.t. CGP 35348. In contrast, i.t. CGP 35348 had no effect on the hot plate test. It is suggested that the input of low threshold afferents innervating mechanoceptors is tonically inhibited by the GABA system through B-type receptors, and blockade of this system results in mechanical hypersensitivity that is similar to mechanical allodynia (painful response to innocuous stimulation) observed in humans.
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PMID:Intrathecal gamma-aminobutyric acidB (GABAB) receptor antagonist CGP 35348 induces hypersensitivity to mechanical stimuli in the rat. 771 32

The nucleus paragigantocellularis lateralis (PGi) in the rostral ventral medulla is implicated in several functions including cardiovascular control, respiration, pain and analgesia. More recent studies implicate this region in alertness and attention as well, by virtue of its prominent projections to the nucleus locus coeruleus (LC). To investigate information that is integrated in the PGi, we used tract tracing to examine brain and spinal projections to this region. Afferents to PGi were found to be functionally diverse and topographically organized. Projections to the retrofacial PGi are primarily autonomic in nature. A wider range of inputs were found to target the rostral (juxtafacial) aspect of the PGi, including brain nuclei involved in the processing of somatosensory and auditory stimuli, as well as autonomic areas. Efferent projections to the LC were also examined in detail. Neuropharmacology experiments revealed that the PGi provides a potent excitatory amino acid input to the LC and an inhibitory input acting at alpha 2 receptors on LC neurons. PGi neurons projecting to the LC stained for markers of adrenaline, enkephalin, GABA and corticotropin releasing factor. Finally, some PGi neurons collateralize to innervate both the LC and the spinal cord. These results suggest that the LC may function in parallel to peripheral autonomic systems providing a cognitive complement to sympathetic function, and that the PGi may integrate a wide range of inputs to facilitate adaptive responses to urgent environmental events.
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PMID:Integration in the ventral medulla and coordination of sympathetic, pain and arousal functions. 773 66

The effects of the nucleus central lateralis (CL) on the unit discharges evoked by the splanchnic afferents in the posterior group of thalamic nuclei (PO) were studied with extracellular microelectrode techniques. In 35 cate, 96 units (98%) producing evoked discharges in PO with the latency range of 30-150ms were observed. The evoked discharges of 69 units in PO were depressed by stimulating CL with a short train of electric pulse through a bipolar electrode, but the other 27 units were uninfluenced. The inhibition of CL can be classified into 3 forms: the instant inhibition, the delayed inhibition and the continued inhibition. The injection of picrotoxin (1%, 40 microliters) into lateral ventricles of the brain could invert the inhibitory effects of PO cells caused by stimulating CL. The results suggest that there may be direct nervous pathway from CL to PO and some of these neurons may function with GABA as neurotransmitter. The CL may execute the instant inhibition through the nervous pathway. It is concluded that CL has inhibitory effect on visceral pain and GABA is involved in the inhibitory process.
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PMID:[The effects of nucleus central lateralis on the unit discharges in posterior group of thalamic nuclei evoked by splanchnic afferents in cats]. 775 Jan 72

The number of GABA-like immunoreactive (LI) cells in lamina I-III of the rat spinal cord was significantly decreased bilaterally 48-72 h after photochemical induction of transient spinal cord ischemia compared to sham-operated controls. No significant changes in the number of GABA-LI cells were observed at cervical level. The number of GABA-LI cells was restored 2 weeks after ischemia. These data, together with recent behavioral and electrophysiological findings, suggest that decreased intraneuronal GABA levels after spinal cord ischemia may underlie the development of the temporary pain-like response to innocuous mechanical stimuli (allodynia) in rats after transient spinal cord ischemia.
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PMID:Decreased GABA immunoreactivity in spinal cord dorsal horn neurons after transient spinal cord ischemia in the rat. 780 36

The pre-embedding double immunoreaction method was used to study synaptic relations of enkephalinergic and GABAergic neuronal elements in the ventrolateral part of the periaqueductal gray of the Wistar albino rat. The enkephalin-like neuronal elements were immunoreacted by the silver-gold intensified peroxidase-antiperoxidase method and the GABA-like immunoreactive neurons were immunoreacted by the unintensified peroxidase-antiperoxidase method. GABA-like immunoreactive neuronal somata were post-synaptic to both the enkephalin-like immunoreactive and the non-immunoreactive axon terminals. Enkephalin-like immunoreactive axon terminals were found to make synapses with GABA-like immunoreactive and non-immunoreactive dendrites. The synapses between the two kinds of chemically characterized neurons appeared to be both asymmetrical and symmetrical. Possible functional activity related to pain modulation, and synaptic relations between the enkephalinergic and GABAergic neurons in the periaqueductal gray and the dorsal raphe nucleus, are discussed.
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PMID:Immunoelectron microscopy of enkephalinergic innervation of GABAergic neurons in the periaqueductal gray. 788 16

The phantom-pain syndrome model was used to examine the effects of phenazepam, sydnocarb and their combination in chronic oral administration. Phenazepam was shown to have no effects on the development of the phantom-pain syndrome. Sydnocarb arrested the progression of the pain syndrome, reduced its symptoms, alleviated inflammatory manifestations and extremity edema. The agent increased animals' excitability. When their combination was used, the clinical signs of the pain syndrome developed in the same way as with sydnocarb alone. At the same time phenazepam decreased the animals' aggression and excitability caused by sydnocarb. It is suggested that enhancing the efficiency of inhibitory GABAergic processes may result in lower clinical signs of the phantom-pain syndrome in case of involvement of brain catecholaminergic systems whose activation increases the inhibitory functions of its related GABA. The sympathomimetic action of sydnocarb induces an elevation of norepinephrine concentrations in the nerve endings and postsynaptic receptors, resulting in trophic improvement and restoration of tissue viability.
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PMID:[The effect of fenazepam and sidnocarb in the phantom pain syndrome]. 790 39

The dorsal raphe nucleus (DRN) is an important nucleus in pain modulation. It has abundant 5-HT neurons and many other neurotransmitter and/or neuromodulator containing neurons. Its vast fiber connections to other parts of the central nervous system provide a morphological basis for its pain modulating function. Its descending projections, via the nucleus raphe magnus or directly, modulate the responses caused by noxious stimulation of the spinal dorsal horn neurons. In ascending projections, it directly modulates the responses of pain sensitive neurons in the thalamus. It can also be involved in analgesia effects induced by the arcuate nucleus of the hypothalamus. Neurophysiologic and neuropharmacologic results suggest that 5-HT neurons and ENKergic neurons in the DRN are pain inhibitory, and GABA neurons are the opposite. The studies of the intrinsic synapses between ENKergic neurons, GABAergic neurons, and 5-HT neurons within the DRN throw light on their relations in pain modulation functions, and further explain their functions in pain mediation.
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PMID:The dorsal raphe: an important nucleus in pain modulation. 792 1


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