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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anatomical and electrophysiological studies have demonstrated that enkephalinergic, noradrenergic, and serotonergic pathways projecting from the brain-stem to the dorsal horn inhibit nociceptive transmission at the spinal level. Previous attempts to delineate interactions between opioids, norepinephrine (NE), and serotonin (5-HT) in the production of spinal analgesia have produced conflicting results. The present study determined the effect of intrathecal (i.t.) pretreatment with opioid, NE, and 5-HT antagonists upon i.t. monoamine- and morphine-induced antinociception as assessed with the rat tail-flick model. Naloxone, at a dose which antagonized i.t. morphine analgesia, had no effect upon i.t. NE but inhibited i.t. 5-HT antinociception. Corynanthine or yohimbine (NE antagonists) reduced analgesia elicited by i.t. NE but not morphine, while pretreatment with methysergide or ketanserin (5-HT antagonists) attenuated both i.t. 5-HT- and morphine-induced antinociception. These results suggest that (1) an opioid link mediates spinal 5-HT but not NE antinociception, and (2) 5-HT but not NE participates in spinal morphine analgesia.
Pain 1988 Jul
PMID:Opioid-monoamine interactions in spinal antinociception: evidence for serotonin but not norepinephrine reciprocity. 284 36

The effects of the alpha-adrenoceptor antagonists prazosin, phentolamine and yohimbine upon 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)-induced analgesia were tested in the hot-plate, tail-flick and shock-titration tests of nociception with rats. Intrathecally injected yohimbine and phentolamine blocked or attenuated the analgesia produced by systemic administration of 5-MeODMT in all three nociceptive tests. Intrathecally administered prazosin attenuated the analgesic effects of 5-MeODMT in the hot-plate and tail-flick tests, but not in the shock titration test. Intrathecal yohimbine showed a dose-related lowering of pain thresholds in saline and 5-MeODMT-treated animals. Phentolamine and prazosin produced normal dose-related curves in the hot-plate test and biphasic effects in the shock titration and tail-flick tests. These results demonstrate a functional interaction between alpha 2-adrenoceptors and 5-HT agonist-induced analgesia at a spinal level in rats.
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PMID:5-Methoxy-N,N-dimethyltryptamine-induced analgesia is blocked by alpha-adrenoceptor antagonists in rats. 287 97

The antinociceptive role of spinal serotonin (5-HT) neurons descending from 5-HT cells near the ventrolateral surface of the medulla oblongata was investigated by stimulating these cells in normal rats, in rats with generalized or selective chemical ablation of 5-HT nerves, and in rats with postsynaptic blockade of 5-HT receptors. Electrical stimulation of the lateral medulla elicited analgesia in normal rats; the increase in pain threshold was proportional to the intensity and to the frequency of stimulation. In addition, microinjection of kainic acid or L-glutamate at the same sites also produced analgesia. However, generalized destruction of CNS 5-HT nerves produced by intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) or selective destruction of spinal 5-HT nerves produced by intraspinal injection of 5,7-DHT reduced the magnitude of the antinociceptive responses to electrical stimulation. Postsynaptic blockade of CNS 5-HT receptors produced by intraventricular injection of cyproheptadine also reduced the stimulation-produced analgesia. The specificity of the lesions for 5-HT nerves is demonstrated by the lack of effect on the levels of noradrenaline in the same brain regions. The results indicate that the activity of 5-HT nerve cells adjacent to the ventrolateral surface of the medulla oblongata and projecting to the spinal cord serves to elevate pain threshold.
Pain 1988 Apr
PMID:The antinociceptive role of a bulbospinal serotonergic pathway in the rat brain. 289 26

The effect of ICS 205-930 (ICS), a specific 5-HT3 antagonist, was studied on carrageenan (CAR)-induced rat paw inflammation to assess the involvement of endogenous released serotonin (5-HT) in the observed hyperalgesia. Studies were performed using a behavioural test, measuring the threshold stimulus necessary to elicit vocalization by gradually increasing pressure applied to the paw. When administered (s.c., in the CAR-injected paw) either 20 min before, simultaneously or 20 min after CAR, ICS (10(-11) mol/kg, i.e., 3.2 ng/kg) completely prevented the hyperalgesia in both the injected and non-injected hind paws. This effect was prolonged for 90 min, equivalent to the effect on CAR on 5-HT release. Moreover, ICS increased the vocalization threshold over the pre-drug values in normal and CAR-treated rats when injected both 20 min before and simultaneously with the polysaccharide. On the contrary, it did not reduce the hyperalgesia, when injected 2 h after CAR. ICS had no effect at any time of administration on paw oedema. These results suggest that the early inflammatory sensitization of peripheral nociceptors is mainly dependent on the release of serotonin and that the hyperalgesic effect of the monoamine involves 5-HT3(M) receptors which do not seem to be involved in the early development of oedema.
Pain 1989 Feb
PMID:Influence of a specific 5-HT3 antagonist on carrageenan-induced hyperalgesia in rats. 291 5

The tail flick assay was used to evaluate pain perception in mice treated acutely with either of the two classical antidepressant drugs (AD) imipramine or amitriptyline, or the atypical antidepressant iprindole. A sustained hypoalgesic effect, sensitive to the opiate antagonist naloxone, was detected for the AD used in this study. Administration of the aminopeptidase inhibitor bestatin or the enkephalinase blocker thiorphan made subeffective doses of AD hypoalgesic. This synergistic effect was reversed by naloxone. The antinociceptive action of the AD wore off in mice rendered tolerant to morphine by subcutaneous implantation of a pellet of the opiate. Subchronic treatment with p-chlorophenylalanine did not alter the effect of AD on pain perception, but in animals whose serotonin (5-HT) receptors were blocked by methysergide AD did not produce any change in pain threshold. It was concluded on the basis of these findings that short-chain opioids and 5-HT appear to have a role in the hypoalgesic effect of either classical or atypical AD.
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PMID:Hypoalgesia induced by antidepressants in mice: a case for opioids and serotonin. 294 98

The tail-flick and increasing temperature hot-plate tests were employed to study the effects of acute or chronic treatment with zimelidine, alaproclate or chlorimipramine on nociception and response to 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) in mice. A single dose of the serotonin (5-HT) uptake inhibitors produced antinociception in the hot-plate test but not in the tail-flick test. After chronic administration, reduced tail-flick latencies were demonstrated 24, 48, 72 and 144 h after withdrawal of zimelidine treatment, 48 h after withdrawal of alaproclate and 48 and 96 h after withdrawal of chlorimipramine treatment. The hot-plate response temperatures were slightly lowered after chronic zimelidine treatment but not after treatment with alaproclate or chlorimipramine. The response to 5-MeODMT was not altered by a single dose of the 5-HT uptake inhibitors, however, after withdrawal of chronic treatment this response was increased in the tail-flick test but not in the hot-plate test. It was concluded that acute and chronic treatment with 5-HT uptake inhibitors modulate nociception differently, and that chronic treatment induces supersensitivity of spinal postsynaptic 5-HT receptors. Different modulation of different 5-HT receptor subpopulations by these compounds may possibly contribute to the test-dependent results.
Pain 1988 Mar
PMID:Acute and chronic treatment with selective serotonin uptake inhibitors in mice: effects on nociceptive sensitivity and response to 5-methoxy-N,N-dimethyltryptamine. 296 34

Numerous anatomical, pharmacological and electrophysiological data described in the literature indicate that spinal enkephalinergic and serotoninergic systems are probably involved in the control of nociceptive inputs from the periphery to the cerebral cortex. However, reported evidence was generally indirect and did not provide a real demonstration of the physiological participation of these neurones in pain control. This led us to select appropriate experimental approaches for studying directly the activity of spinal enkephalinergic and serotoninergic systems in animals (rat, cat) submitted to noxious stimuli. Owing to two catheters introduced into the subarachnoidal space of anesthetized rats, it was possible to perfuse the whole spinal cord with an artificial cerebro-spinal fluid and thus collect the neuroactive compounds released by spinal neurones (at least those in superficial layers) under various experimental conditions. Using this technique, we observed that some (but not all) nociceptive stimuli such as intense pinching of the muzzle, intraperitoneal injection of acetic acid or noxious heat applied to the muzzle or the tail induced a significant increase in met-enkephalin release from the spinal cord (see fig. 2). Similar effects were observed following the blockade of enkephalin catabolism by thiorphan and bestatin (see fig. 1) indicating that they were not due to some alteration of peptidase activities but really involved the activation of spinal enkephalinergic systems. Since cervical cord transection suppressed the stimulatory action of noxious stimuli on spinal met-enkephalin release, it could be proposed that the mechanisms involved were not limited to the cord but depended on supraspinal structures. Bulbo-mesencephalic serotoninergic neurones projecting to the spinal cord might well correspond to such structures (or at least to some of them) since nociceptive stimuli (such as noxious heat applied to the tail) also evoked a marked increase of serotonin (5-HT) release at the spinal level (fig. 3). Such observations together with indirect evidence reported in the literature suggested therefore that the activation of spinal enkephalinergic systems triggered by noxious stimuli might result from excitatory influence due to descending serotoninergic projections. However, in vitro studies using slices of the dorsal zone of the rat lumbar cord did not reveal any stimulatory effect of 5-HT on the spontaneous or K+-evoked release of met-enkephalin (fig. 4).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[The spinal enkephalinergic and serotoninergic systems in the control of transmission of nociceptive messages]. 299 51

In anaesthetised rats, 63 raphe-spinal units in nucleus raphe magnus (NRM) have been identified by means of electrophysiological methods and further classified into serotonergic (5-HT) and non-5-HT units according to their conduction velocity and spontaneous discharge rate. All units, except one, showed either excitatory (n = 39) or inhibitory (n = 23) responses to noxious heating of the tail with hot water at 52 degrees C. The threshold temperature was around 44 degrees C and both types of responses increased with stepwise increases in temperature. The excitatory or inhibitory responses of raphe-spinal units induced by noxious heating of the tail correlated well with those elicited by noxious pinching, but did not correlate with the different transmitter populations (5-HT or non-5-HT) of the NRM unit. The effects of morphine or Fentanyl administration on the heat-induced responses of NRM units was observed. The possible involvement of NRM raphe-spinal units in 'diffuse noxious inhibitory controls' (DNICs) was discussed, particularly in relation to the 'lifting of DNICs' produced by morphine.
Pain 1986 Aug
PMID:The modification by systemic morphine of the responses of serotonergic and non-serotonergic neurons in nucleus raphe magnus to heating the tail. 302 Apr 87

Experiments performed in our laboratory, using electrical stimulation combined with microinjection of drugs in the dorsal midbrain central grey (CG) of the rat, evidenced that direct stimulation of GABA receptors with locally administered gamma-aminobutyric acid (GABA) or the GABAA receptor agonists 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol, isoguvacine and muscimol raised the aversive threshold, defined as the lowest electrical current intensity inducing flight or escape behaviour when applied to the dorsal CG. The GABAB receptor agonist baclofen was ineffective. Also, enhancement of endogenous GABA action through local injection of the benzodiazepines chlordiazepoxide and midazolam or of pentobarbital resulted in anti-aversive effects. Ro 15-1788 antagonized both chlordiazepoxide and midazolam, suggesting benzodiazepine receptor mediation. In contrast to pro-GABAergic drugs, microinjection of the GABA antagonists bicuculline and picrotoxin into the CG elicited flight behaviour, like the electrical stimulation. Similar experiments with drugs influencing serotonergic neurotransmission evidenced that intra-CG microinjection of serotonin (5-HT) or of the direct 5-HT receptor agonist 5-methoxy-N,N-dimethyltryptamine increased the aversive threshold. The anti-aversive effect of 5-HT was potentiated by the selective inhibitor of 5-HT neuronal uptake, zimelidine. Also, the latter drug increased the aversive threshold when given alone. The anti-aversive effect of 5-HT was antagonized by local pretreatment with either metergoline or ketanserin, the latter being a selective blocker of 5-HT2 receptors. In contrast to the GABA antagonists mentioned above, the 5-HT receptor blockers did not evoke aversive behaviour per se. Therefore, both GABAergic and serotonergic mechanisms are likely to play an inhibitory role in the dorsal CG integrating aversive behaviour. The former seem to act tonically, whereas 5-HT would act in a phasic way. The implications of these results for the pathophysiology and drug treatment of chronic anxiety, panic states and pain disorders are briefly discussed.
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PMID:Modulation of the brain aversive system by GABAergic and serotonergic mechanisms. 302 64

The effects of changes in central serotoninergic transmission on clonidine analgesia were assessed in monkeys. The minimum electrical current required for producing jaw opening is referred to as the pain threshold. Pain was induced by electrical stimulation of tooth pulp afferents. In the first series of studies, intracerebroventricular administration of clonidine (5-30 micrograms) produced dose-dependent analgesia in monkeys. The clonidine-induced analgesia was abolished or attenuated by prior injection of the animals with p-chlorophenylalanine or 5,7-dihydroxytryptamine into the third cerebral ventricle. On the other hand, pretreatment of the animals by injecting 5-HT or its precursor 5-hydroxytryptophan into the cerebral ventricle potentiated the clonidine-induced analgesia in monkeys. In the second series of experiments, administration of clonidine (1-10 micrograms) into the diencephalic periventricular gray (of the anterior hypothalamic portion), the periaqueductal gray, or the dorsal raphe nuclei also produced dose-dependent analgesia in monkeys. The analgesia induced by clonidine injection into the diencephalic periventricular gray or the periaqueductal gray was effectively antagonized by pretreatment of the animals by injecting two 5-HT receptor antagonists (such as ketanserine and methysergide) into the diencephalic periventricular gray or the periaqueductal gray. The clonidine-induced analgesia in monkeys was not affected by pretreatment of the animals with injections of either ketanserine or methysergide into the dorsal raphe nuclei. The results suggest that the functional activity of central 5-HT neurons correlate well with the analgesic sensitivity of clonidine microinjected centrally. In addition, the analgesia induced by clonidine microinjected into the diencephalic periventricular gray or the periaqueductal gray was mediated by the 5-HT receptors at the site of injection.
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PMID:Changes in central serotoninergic transmission affect clonidine analgesia in monkeys. 303 80


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