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BACKGROUND: Pain is a dynamic phenomenon resulting from the activity of both excitatory (e.g. sensitization) and inhibitory endogenous modulation systems. Preliminary experimental studies have shown diminished pain sensitivity in schizophrenia patients. The objective of the study was to investigate the role of excitatory and inhibitory systems on pain perception in schizophrenia. METHODS: Participants were 23 patients with a schizophrenia-spectrum disorder (DSM-IV criteria) and 29 healthy volunteers, who did not differ in age, sex or ethnicity. Excitatory and inhibitory systems were elicited using a temporal summation test (Peltier thermode) administered before and after activation of the diffuse noxious inhibitory control (DNIC) by means of a cold-pressor test. RESULTS: Time was a significant predictor of pain scores in controls, but not in patients. That is, pain ratings increased during the tonic thermal stimulation among controls but not in schizophrenia patients. When correlation coefficients (between time and pain ratings) for patients and controls were compared, the correlation coefficient emerged as significantly weaker in the schizophrenia group (Z=12.04; p=0.0001), suggesting a lack of sensitization in schizophrenia. DNIC was similar in magnitude in both patients and controls. CONCLUSIONS: Diminished pain sensitivity in schizophrenia may be related to abnormal excitatory mechanisms, but not to DNIC. More studies are needed to better characterize the neurophysiological and neurochemical mechanisms involved in the lack of sensitization in schizophrenia.  相似文献
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Although electrical stimulation of supraspinal structures and local large fibres is known to inhibit the responses of nociceptive neurones, comparable studies on thermoreceptive cells have not been made. We have studied the effects of nucleus raphe magnus (NRM) and segmental stimulation on cold and warm responsive neurones in trigeminal nucleus caudalis of both the rat and cat. All 48 neurones (46 cold and 2 warm) tested in the cat and 24 cold neurones in the rat were unaffected by the NRM at a variety of stimulation parameters. However, segmental stimulation inhibited420 neurones in the cat and1126 cells in the rat. The results show the selectivity of the inhibition following NRM stimulation.  相似文献
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The effect of exogenous opiates upon diffuse noxious inhibitory controls (DNIC) was investigated in intact anaesthetized rats. 58 convergent neurones, responding to both noxious and innocuous stimuli applied to their cutaneous receptive fields, were recorded at the lumbar level. These cells received A- and C-peripheral fibre inputs as shown by electrical stimulation of their receptive fields and were mainly located in the medial part of the dorsal horn.The immersion of the distal two-thirds of the tail in hot water (52 °C) induced strong inhibition of the responses to both A-(23%) and C-(69%) fibres. Post-effects of long duration were commonly observed after cessation of the conditioning stimulus.While systematic injection of morphine at a low dose-range (0.1–1 mg/kg) did not significantly affect the unconditioned responses, the DNIC-mediated inhibitions were profoundly altered.(a) DNIC of responses to C fibres were dose-dependently (P < 0.01) lifted by morphine: (b) the post-effects observed after cessation of conditioning stimuli were dose-dependently (P < 0.01) diminished; (c) DNIC of responses to A-fibre were similarly altered but this effect was less significant (P < 0.05); (d) DNIC of responses to sustained moderate pressure were greatly diminished by morphine (P < 0.01); and (e) these effects were specific since they were antagonized by the opiate antagonist, naloxone. In addition, they were shown to be stereospecific since while the dextrogyre stereoisomer, dextrorphan, was ineffective the levogyre derivative, levorphanol, induced a significant lifting of DNIC.It is concluded that morphine decreases the supraspinal inhibitory controls of dorsal horn convergent neurones, at least when these controls are triggered by noxious stimuli. Assuming that a basic somatosensory background activity (noise) is transmitted to higher centres by dorsal horn convergent neurones, and that the pain-signalling message is the contrast between the activity of the segmental pool of neurones induced by the noxious stimulus and the DNIC-mediated silence of the remaining neuronal population, it is proposed that, by a reduction in DNIC, low-dose morphine could restore the initial level of background activity, the final result being analgesia.  相似文献
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In rats and cats anaesthetized with urethane a comparison was made of the inhibitory effects of raphe magnus (NRM) and segmental (facial skin) stimulation on neurones in nucleus caudalis excited by tooth pulp stimulation. The upper and lower ipsilateral incisor teeth were used in rats (176 neurones) and the corresponding canine teeth in cats (34 neurones). The recording sites were located in all layer of nucleus caudalis and in the underlying reticular formation. Both the evoked responses and the conditioning effects were similar in the two species. Both forms of conditioning inhibited about half the neurones tested but only a small proportion was influenced from both sources. NRM stimulation had almost identical effects on neurones driven from upper teeth or from lower teeth and tended to act on those cells with longer latencies. Segmental stimulation influenced the majority of shorter latency cells and produced greater inhibitions of upper tooth pulp neurones. Diffuse noxious inhibitory controls were also observed for certain neurones.  相似文献
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Diffuse Noxious Inhibitory Controls (DNIC) were investigated in anaesthetized intact rats, with or without p-chlorophenylalanin (pCPA) pretreatment. Dorsal horn convergent neurones responding to both noxious and non-noxious stimuli applied to their excitatory receptive field located on the distal part of the hindlimb, were recorded in the lumbar spinal cord. These cells received Aα and C fibre inputs as shown by electrical stimulation of their receptive field.In control animals, the evoked responses to C fibre inputs coulb be strongly inhibited by various noxious stimuli applied to widespread areas of the body: the inhibitory effects induced by intraperitoneal administration of bradykinin, pinch applied to the tail or muzzle and noxious heat applied to the tail were of 77%, 87%, 83% and 61% respectively. Long-lasting post-effects were seen in most cases after cessation of the application of the conditioning stimulus.Pretreatment with pCPA (300 mg/kg, i.p., 3 days) resulted in a strong reduction of DNIC. The inhibitory effects induced by intraperitoneal administration of bradykinin, pinch applied to the tail or muzzle and noxious heat applied to the tail were reduced by 47%, 63%, 87% and 63%, respectively. The post-effects were also reduced both in terms of magnitude and duration.These results strongly suggest that serotonergic pathways are partially involved in  相似文献
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The involvement of serotonergic mechanisms in diffuse noxious inhibitory controls (DNIC) acting on dorsal horn convergent neurones has been studied in the anaesthetized rat. 35 neurones activated by transcutaneous electrical stimulation of their hindpaw receptive fields giving clear large A-fibre and C-fibre responses were recorded. These activities were conditioned by DNIC, evoked by either noxious heat applied to the tail or noxious pinch of the nose. Cinanserin (4 mg/kg i.v.) and metergoline (5 mg/kg i.v.), serotonin (5-HT) receptor blockers, strongly reduced the inhibitory effects of DNIC whilst having no significant effect on the non-conditioned responses. 5-Hydroxytryptophan, a precursor for 5-HT synthesis, significantly potentiated the effect of DNIC. These results indicate an important role for descending serotonergic pathways in DNIC. The functional role of this system is discussed.  相似文献
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Extracellular single unit recordings were obtained from spinal cord dorsal horn neurons in halothane-anesthetized rats. Inhibitory effects induced by noxious mechanical or electrical stimuli applied to a remote area of the body surface were assessed on the spontaneous or evoked activity of these cells. Noxious mechanical stimulation inhibited 59% of the cells receiving nociceptive inputs (wide dynamic range and nociceptive specific) but only 5% of the other cell types. Inhibition produced by mechanical stimulation lasted for the full duration of stimulus application (up to 30 s) whereas inhibition produced by electrical stimulation lasted less than 500 ms. Increasing the depth of anesthesia was found to depress or abolish the inhibition.  相似文献
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Activity produced by direct microelectrophoretic application of glutamate onto 19 convergent neurones in trigeminal nucleus caudalis, was strongly depressed during and after the application of heterotopic noxious conditioning stimuli: noxious heat (52 °C) applied to the tail, noxious pinches applied to the tail or hindpaws and intraperitoneal injections of bradykinin produced mean reductions in activity of 80–90%. The same noxious conditioning stimuli had no effect on the activities of any of 5 noxious-only or 5-non-noxious-only neurones. These effects were similar to those previously reported to influence peripherally evoked activities of nucleus caudalis convergent neurones and which have been termed diffuse noxious inhibitory controls (DNIC). It is therefore proposed that DNIC act on nucleus caudalis convergent neurones by a final post-synaptic inhibitory mechanism involving hyperpolarisation of the neuronal membrane. Consistent with this hypothesis, it was also found that the noxious conditioning stimuli could restore firing of convergent neurones which had been excessively depolarized by large doses of glutamate.  相似文献
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