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

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

Nucleus raphe magnus contains a large population of raphe-spinal serotonergic neurons that are thought to be involved in descending control of pain transmission and the modulation of opioid analgesia. Intracellular recordings were made from nucleus raphe magnus neurons in the slice preparation. Cells were divided into two groups, primary and secondary cells, based on the action potential waveform and response to opioids, as reported previously. In some experiments, cells were filled with biocytin and 5-hydroxytryptamine-containing cells were identified immunohistochemically. Of the primary cells that were filled with biocytin, 93% stained for 5-hydroxytryptamine; 90% of biocytin-filled secondary cells were unlabeled for 5-hydroxytryptamine. Previous studies have shown that primary cells are disinhibited by opioids; the finding that most primary cells are serotonergic suggests that at least some 5-hydroxytryptamine-containing neurons in the nucleus raphe magnus are excited by opioid analgesics. 5-Hydroxytryptamine hyperpolarized cells in both primary and secondary cell groups. The 5-hydroxytryptamine agonists (+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide and 5-carboxamidotryptamine mimicked this action of 5-hydroxytryptamine, indicating that the 5-hydroxytryptamine 1A-subtype mediated this hyperpolarization. The hyperpolarization was mediated by an increase in potassium conductance that rectified inwardly. Local electrical stimulation of afferents evoked an inhibitory postsynaptic potential in primary cells. The inhibitory postsynaptic potential reversed polarity at the potassium equilibrium potential and was blocked by 5-hydroxytryptamine 1A receptor antagonists. It is proposed that the 5-hydroxytrypamine1A receptor on serotonergic primary cells may function as an autoreceptor to regulate the activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation by serotonin of the neurons in rat nucleus raphe magnus in vitro. 810 40

The effects of treatment with para-chloro-phenyl-alanine (PCPA) (100 mg/kg i.p. for 4 days) were studied on the hot-plate test and on brain 5-HT binding in phenazone treated rats. Phenazone per se induces analgesia in the hot-plate test and decreases the number of cortical and pontine 5-HT binding sites A pre-treatment with PCPA prevents both the analgesic effect and the reduction of 5-HT binding sites caused by phenazone. These data suggest that the brain serotonin system may play a role in phenazone-induced antinociception.
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PMID:The role of serotonin brain receptors in the analgesic effect of phenazone. 822 35

Serotonin is one of the many neurotransmitters involved in nociception. Serotonin antagonists may therefore reduce postoperative pain. In the present study we examined whether the new 5-HT3 receptor antagonist GR 38032F (ondansetron) reduced postoperative pain after minor surgery and compared its effectiveness with that of lysin acetyl salicylate (Aspisol). METHODS. A series of 100 patients of both sexes who were undergoing minor surgery were enrolled in this study. Patients who did not need analgesic medication within the first 3 h after surgery were regarded as "dropouts", and the rest were studied for 24 h. In a preliminary study (n = 19) patients received ondansetron i.v. in increasing dosages (6, 12, 24, 48, 96 and 128 micrograms.kg-1) to evaluate the analgesic potency of this drug. In the main double-blind, randomized, study (n = 81), three groups were formed, and patients received 50 micrograms.kg-1 or 100 micrograms.kg-1 ondansetron i.v. or saline only i.v. Analgesia was evaluated by visual analogue (VAS) and verbal rating scales (VRS). If pain persisted patients received 1.8 g lysin acetylsalicylate (LAS) i.v. RESULTS. There were 6 (out of 19) patients in the preliminary study and 36 (out of 81) patients in the main study who were dropouts; that is to say they did not require any analgesic medication within the first 3 h, but 12 of these dropouts needed analgesic medication more than 3 h after end of surgery. Pain was reduced by 82% from baseline in 7 out of 13 patients in the preliminary study (11 men, 2 women). In the main study (n = 45, 28 men, 17 women) 100 micrograms.kg-1 ondansetron did not show a better analgesic effect than 50 micrograms.kg-1, and there was no significant difference between ondansetron and saline. VAS showed a reduction in pain from 6.9 +/- 2.0, 6.8 +/- 1.5 and 6.6 +/- 1.8 to 4.1 +/- 2.4, 3.4 +/- 2.2 and 3.4 +/- 2.1 in the 50 micrograms.kg-1, 100 micrograms.kg-1 and saline groups, respectively, within 60 min after i.v. application. VRS diminished from 2.5 +/- 0.5, 2.5 +/- 0.6 and 2.4 +/- 0.5 to 1.7 +/- 0.7, 1.5 +/- 0.8 and 1.5 +/- 0.7, respectively. There were 26 patients who experienced no pain relief in response to ondansetron or placebo and who therefore received LAS, and 21 of these then experienced significant pain reduction. CONCLUSION. Pain after minor surgery does not appear to be a major problem. For 42 out of 100 patients no analgesics were needed within the first 3 h after end of surgery. Ondansetron was no more effective than placebo in reducing postoperative pain. Lysin acetylsalicylate, however, may be an effective alternative to opioids for the treatment of postoperative pain.
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PMID:[Postoperative pain therapy. The efficacy of a serotonin antagonist (GR 38032F;ondansetron) and the prostaglandin synthesis inhibitor lysin acetylsalicylate (Aspisol)]. 827 93

Leaf and bark extracts of Byrsonima crassifolia displayed concentration-dependent, spasmogenic effects on rat fundus in vitro and biphasic effects on rat jejunum and ileum in vitro. Dose-related in vivo effects in intact rats using hippocratic screening were: decrease in motor activity, mild analgesia, back tonus, enophthalmos, reversible palpebral ptosis, ear blanching, Robichaud positive, catalepsy (awake) and strong hypothermia. Rat fundus in vitro was used as the bioassay to carry out an activity-directed separation. Bioactive material was concentrated in a 2% acetic acid leaf extract (HOAcE). Potency of HOAcE was increased by the presence of pargyline in the bathing solution. HOAcE was antagonized noncompetively by 1(1-naphthyl) piperazine (1-NP) and cyproheptadine and antagonized competitively by atropine (ATR). Cumulative concentration-response curves of HOAcE and serotonin (5-HT) did not show significant departure from parallelism (P > 0.1) and 5-HT potency was 6040 times that of HOAcE (95% confidence limits: 4620-7850). Solvent extraction of HOAcE split the spasmogenic activity of HOAcE into two types: (i) high-efficacy, low-potency, n-butanol-extracted, pargyline- and 1-NP-sensitive, ATR-insensitive activity, and (ii) low-efficacy, high-potency, ethyl acetate-extracted, pargyline-insensitive, ATR- and 1-NP-sensitive activity. HOAcE lacked muscarinic and nicotinic effects on rat jejunum and frog rectus abdominis. Results suggest the presence of more than one spasmogenic compound in the plant.
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PMID:Pharmacological and chemical screening of Byrsonima crassifolia, a medicinal tree from Mexico. Part I. 841 47

Fluoxetine, zimelidine, sertraline, paroxetine, fluvoxamine, indalpine and citalopram are the selective inhibitors of serotonin uptake that have been most widely studied. Some of these compounds are or have been used clinically in the treatment of mental depression, obsessive-compulsive disorder and bulimia, and therapeutic benefit has been claimed in additional diseases as well. By blocking the membrane uptake carrier which transports serotonin from the extracellular space to inside the serotonin nerve terminals, these compounds increase extracellular concentrations of serotonin and amplify signals sent by serotonin neurons. Because serotonin neurons are widespread in the central nervous system, the functional consequences of blocking serotonin uptake are diverse, but are generally subtle. Animals treated with serotonin uptake inhibitors look normal in gross appearance, but effects such as reduced aggressive behavior, decreased food intake and altered food selection, analgesia, anticonvulsant activity, endocrine changes and neurochemical changes have been demonstrated and characterized. Serotonin uptake inhibitors have helped in revealing some dynamics of serotonin neurons; for example, when uptake is inhibited and extracellular serotonin concentration increases, presynaptic as well as postsynaptic receptors for serotonin are activated to a greater degree. A consequence of increased activation of autoreceptors on serotonin cell bodies and nerve terminals is a reduction in firing of serotonin neurons and a decrease in serotonin synthesis and release. The result is a limit on the degree to which extracellular serotonin and serotonergic neurotransmission are increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonin uptake inhibitors: uses in clinical therapy and in laboratory research. 854 37

Results from studies of pharmacotherapies for primary alcoholism are reviewed, including selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (e.g. fluoxetine), opiate antagonists (e.g. naltrexone) and dopamine agonists (e.g. bromocriptine). Because there is considerable comorbidity between alcohol dependence, anxiety, and affective disorders, results from studies of medications used to treat these psychiatric disorders are also reviewed, including the 5-HT agonist buspirone and the noradrenergic agent desipramine. The neurobehavioural model of alcohol dependence implies that combinations of medications may lead to more effective treatment; thus, identifying subtypes of alcoholic patients will be important in determining which therapies or combinations of therapy will be most effective in treating alcohol dependence. For example, in an ongoing study, we are attempting to subtype an alcoholic population for treatment selection by measuring endogenous opioid activity. Because endogenous opioids are involved in analgesia, we exposed male and female subjects with alcoholism [some of whom had post-traumatic stress disorder (PTSD)] to cold-induced pain and measured their response before and after administration of naloxone or placebo. The naloxone injection reduced pain response. In addition, women who have PTSD are much more sensitive to stress, which may be related to levels of brain opioid activity.
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PMID:Neurobehavioural basis for the pharmacotherapy of alcoholism: current and future directions. 873

Tramadol is a cyclohexanol derivative with mu-agonist activity. It has been used as an analgesic for postoperative or chronic pain since the late 1970s, and became one of the most popular analgesics of its class in Germany. International interest has been renewed during the past few years, when it was discovered that tramadol not only acts on opioid receptors, but also inhibits serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (norepinephrine) reuptake. This review aims to provide a risk-benefit assessment of tramadol in the management of acute and chronic pain syndromes. Tramadol has been used intraoperatively as part of balanced anaesthesia. Such use is under discussion, however, as it was associated with a high incidence of intraoperative recall and dreaming, and postoperative respiratory depression has been described after intraoperative administration of high doses. Postoperatively, intravenous and intramuscular tramadol has been used with good efficacy. Analgesic doses were comparable with pethidine (meperidine) and 10 times higher than morphine. Nausea and vomiting were the most frequently reported adverse effects. In controlled studies, haemodynamic and respiratory parameters were only minimally impaired. The risk of severe respiratory depression in typical dosages is negligible in comparison with other opioids used for postoperative pain management. Tramadol has been used with good results for the management of labour pain without respiratory depression of the neonate. It was also effective for the treatment of pain from myocardial ischaemia, ureteric colic and acute trauma. Good results have been published for cancer pain management with tramadol in several studies. The potential for abuse or addiction seems to be minimal, and serious complications have not been reported. For patients with severe pain, the efficacy of morphine is superior, and most patients with adequate analgesia from tramadol had to be changed to a more potent opioid after a few weeks due to increased nociceptive input during tumour progression. Tramadol can be recommended as a safe and efficient drug for step II according to the World Health Organization guidelines for cancer pain management.
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PMID:A risk-benefit assessment of tramadol in the management of pain. 886 61

The effects of drugs selectively effecting central serotonergic systems on immobilization-induced analgesia (SIA) were tested in the rat. The drugs were used in dose ranges previously shown to effect emotional processes. SIA was tested using the tail withdrawal method. It was found that pretreatment of rats with para-chlorophenylalanine (p-CPA), an inhibitor of serotonin synthesis, significantly attenuated SIA, measured immediately after stress session. Ritanserin, a 5-HT2A/2C receptor antagonist, ondansetron, a 5-HT3 receptor antagonist and citalopram, a selective serotonin re-uptake blocker increased the baseline pain threshold, whereas 8-OH-DPAT, a full 5-HT1A receptor agonist and buspirone, a partial 5-HT1A receptor agonist expressing also high affinity towards dopaminergic D2 receptors, were without effect on pain perception and stress induced analgesia. It has been concluded, that modification of SIA by serotonergic drugs probably merely reflects changes in the activity of the 5-HT system on the spinal cord level, with minor, if any, contribution of supraspinal emotional centers.
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PMID:Influence of serotonergic drugs on restraint stress induced analgesia. 886 28

Traditionally, the analgesic action of nonsteroidal anti-inflammatory drugs (NSAIDs) has been explained on the basis of their inhibition of the enzymes that synthesise prostaglandins. However, it is clear that NSAIDs exert their analgesic effect not only through peripheral inhibition of prostaglandin synthesis but also through a variety of other peripheral and central mechanisms. It is now known that there are 2 structurally distinct forms of the cyclo-oxygenase enzyme (COX-1 and COX-2). COX-1 is a constitutive member of normal cells and COX-2 is induced in inflammatory cells. Inhibition of COX-2 activity represent the most likely mechanism of action for NSAID-mediated analgesia, while the ratio of inhibition of COX-1 to COX-2 by NSAIDs should determine the likelihood of adverse effects. In addition, some NSAIDs inhibit the lipoxygenase pathway, which may itself result in the production of algogenic metabolites. Interference with G-protein-mediated signal transduction by NSAIDs may form the basis of an analgesic mechanism unrelated to inhibition of prostaglandin synthesis. These is increasing evidence that NSAIDs have a central mechanism of action that augments the peripheral mechanism. This effect may be the result of interference with the formation of prostaglandins within the CNS. Alternatively, the central action may be mediated by endogenous opioid peptides or blockade of the release of serotonin (5-hydroxytryptamine; 5-HT). A mechanism involving inhibition of excitatory amino acids of N-methyl-D-aspartate receptor activation has also been proposed.
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PMID:The mechanisms of action of NSAIDs in analgesia. 892 54


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