Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study examined patterns of analgesia by intracerebroventricular (i.c.v.) or intrathecal (i.t.) administration of the serotonin 5-HT3 receptor agonist, 2-methylserotonin (1-100 micrograms) against acute thermal, mechanical or formalin-induced chemo-inflammatory pain in male rats. Neither i.c.v. or i.t. 2-methylserotonin produced motoric, sedative or respiratory effects. I.c.v. 2-methylserotonin was not analgesic at any dose in the pain assays employed. I.t. 2-methylserotonin produced dose-related analgesia in the formalin test with significant effects at 20-100 micrograms doses. In contrast, only the 100 micrograms dose of 2-methylserotonin produced analgesia against thermal pain, and analgesia was not observed at any dose in the mechanical pain test. The effects of 2-methylserotonin (100 micrograms) in the formalin test were attenuated by pretreatment (10 micrograms i.t.) with the 5-HT3 receptor antagonist MDL-72222, opioid antagonist naloxone or GABA antagonist bicuculline; the 5-HT2-receptor antagonist ketanserin or 5-HT1 receptor antagonist mianserin did not affect 2-methylserotonin-induced analgesia. In the thermal test, i.t. pretreatment with MDL-72222, ketanserin, naloxone or bicuculline, but not mianserin, reduced analgesic effects of 2-methylserotonin (100 micrograms i.t.). These findings suggest that spinal 5-HT3, opioid and GABA receptor systems interact to mediate acute chemo-inflammatory pain, and implicate the interaction of these systems with 5-HT2 receptor substrates in analgesia against acute thermal nociception.
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PMID:Analgesic profile of centrally administered 2-methylserotonin against acute pain in rats. 195 80

The serotonin-containing raphe-spinal pathway has been implicated as playing an important role in analgesia. Several studies, however, have reported the inefficacy of traditional serotonin receptor antagonists at reversing the antinociceptive action of electrical stimulation in the raphe. In the light of recent reports on the existence of several types of 5-HT receptors in rat spinal cord, the present study investigated the ability of two antagonists, selective for two different 5-HT receptors to reverse the effects of focal electrical stimulation of the raphe magnus nucleus in the rat. Electrical stimulation of this nucleus resulted in selective antinociceptive as well as non-selective inhibitory effects on dorsal horn neurones. Both these effects were blocked by the ionophoretic application of a 5-HT1, but not a 5-HT2 receptor antagonist. The study presents data supporting the role of a spinal 5-HT receptor in mediating stimulation-produced analgesia from the nucleus raphe magnus and further, furnishes evidence that the 5-HT1 receptor is involved in antinociception at the spinal level.
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PMID:A 5-HT1-type receptor mediates the antinociceptive effect of nucleus raphe magnus stimulation in the rat. 220 94

beta-Endorphin administered intrathecally (i.t.) in rats produced a dose-dependent elevation in tail-flick latency. Naltrexone administered i.t. as a pretreatment reversed the spinal antinociceptive action of beta-endorphin, suggesting that the opioid interacts directly with spinal opiate receptors. Spinal administration of the alpha 1-adrenoceptor antagonist WB-4101 failed to alter the analgesic effects of the opioid, whereas the alpha 2-adrenoceptor antagonist yohimbine completely blocked beta-endorphin-induced elevations in tail-flick latency. Thus, there is an apparent specificity for the alpha 2-adrenoceptor to mediate the spinal action of beta-endorphin. The 5-HT1 and 5-HT3 receptor antagonists (spiroxatrine and ICS 205-930, respectively) also reversed the analgesic effects of the opioid, while the 5-HT2 receptor antagonist ritanserin only partially blocked beta-endorphin-induced elevations in tail-flick latency. The present results suggest that beta-endorphin produces analgesia at the spinal level via an opiate receptor-mediated interaction with spinal monoaminergic nerve terminals.
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PMID:Spinal beta-endorphin analgesia involves an interaction with local monoaminergic systems. 256 5

Acute exposure to continuous (CCWS) or intermittent (ICWS) cold-water swims elicits non-opioid and opioid forms of analgesia respectively. Intrathecal administration of methysergide blocks ICWS, but not CCWS analgesia. The present study evaluated the role of serotonin (5-HT) receptor subtypes in the mediation of CCWS and ICWS analgesia on the tail-flick and jump tests following administration of methysergide, a non-specific 5-HT antagonist and pirenpirone and ketanserin, two 5-HT2 receptor subtype antagonists. Systemic methysergide was more effective in reducing CCWS analgesia (50-58%, 0.1-1.0 mg/kg) than ICWS analgesia (21%, 5 mg/kg) on both pain tests. Systemic pirenpirone (0.04-0.2 mg/kg) and ketanserin (1-5 mg/kg) were also more effective in reducing CCWS analgesia (43-57%) on both tests than ICWS analgesia (pirenpirone: 0.4 mg/kg, 34%; ketanserin: 5 mg/kg, 21%) on the tail-flick test. Indeed, both 5-HT2 receptor antagonists potentiated ICWS analgesia on the jump test. While serotonin antagonist effects upon hypothermia could not account for CCWS analgesia effects, similar potentiations in ICWS analgesia and hypothermia were observed following pirenpirone and ketanserin. Finally, both 5-HT2 receptor antagonists differentially reduced CCWS hypothermia and potentiated ICWS hypothermia. These data suggest differential serotonergic modulation of the two forms of swim analgesia with opioid-mediated ICWS analgesia acting through spinal 5-HT1 receptors and non-opioid-mediated CCWS analgesia acting through supraspinal 5-HT2 receptors.
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PMID:Reduction in opioid and non-opioid forms of swim analgesia by 5-HT2 receptor antagonists. 260 92

Pirenperone, a new serotonin antagonist with a selective affinity for the 5-HT2 receptor, was administered in conjunction with tests for the antinociceptive effects of morphine sulphate and electrical brain-stimulation at sites in the periaqueductal gray (PAG) and nucleus raphe magnus (NRM). Nociception was assessed by tail-flick latencies in a warm water bath and pirenperone (0.04-0.16 mg/kg) had no effect on baseline scores. When administered prior to morphine, pirenperone (0.16 mg/kg) caused significant attenuation of analgesia induced by morphine. Comparable effects of pirenperone were observed when analgesia was produced by electrical stimulation of the NRM. In contrast, pirenperone had no effect on the analgesic effects of PAG stimulation. This pattern of results suggests that a system involving supraspinal 5-HT2 receptors may modulate some of the antinociceptive effects of morphine and stimulation of the NRM. The differential effects of pirenperone on stimulation-produced analgesia at sites in the NRM and PAG is consistent with separate neural substrates for the analgesia observed from stimulation of these two brain regions.
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PMID:Selective effects of pirenperone on analgesia produced by morphine or electrical stimulation at sites in the nucleus raphe magnus and periaqueductal gray. 308 29

Intracerebroventricular (i.c.v.) injection of highly selective mu opioid receptor agonist ohmefentanyl (OMF) to rats produced dose-dependent antinociception as assessed with the tail flick test. This analgesia could be blocked by intrathecal (i.t.) injection of the 5-HT1A receptor antagonist spiperone or the 5-HT1C/2 receptor antagonist mianserin, but not by the 5-HT2 receptor antagonist 1-NP or the 5-HT3 receptor antagonist ICS 205-930. The results suggest that the descending 5-HT system is involved in mediating spinal mu opioid analgesia via spinal 5-HT1A and 5-HT1C/2 receptors.
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PMID:Spinal serotonin IA and IC/2 receptors mediate supraspinal mu opioid-induced analgesia. 769 28

Besides the important role of emotional factors in the production of psychological-stress-induced analgesia (PSY-SIA), recent attention to the participation of serotonergic (5-HTnergic) neurons in the fear- and anxiety-evoking mechanism led us to examine the effects of 5-HTnergic ligands on PSY-SIA. Pretreatment of mice with 2.0 to 10 mg/kg of methysergide, a 5-HT receptor antagonist, or 1.0 to 10 mg/kg of buspirone, a 5-HT1A receptor partial agonist, dose-dependently suppressed the production of PSY-SIA. Ritanserin, a 5-HT2 receptor antagonist, 1.0 to 5.0 mg/kg, or Y-25,130, a 5-HT3 receptor antagonist, 0.03 and 0.1 mg/kg, also inhibited PSY-SIA dose-dependently, while (+/-)pindolol, a 5-HT1A/1B receptor antagonist, was ineffective at doses up to 3.0 mg/kg. Furthermore, the suppressive effect of PSY-stress on the development of antinociceptive tolerance to morphine was also antagonized by methysergide, buspirone, ritanserin and Y-25,130, but not by (+/-)pindolol. These results suggest that 5-HT receptor (5-HT1A, 5-HT2 and 5-HT3 but not 5-HT1B)-mediated mechanisms play an important role in the production of PSY-SIA.
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PMID:Involvement of serotonergic receptor subtypes in the production of antinociception by psychological stress in mice. 848 1

Risperidone is a novel atypical neuroleptic with a favorable profile of side effects due to its unique pharmacological activity: it exhibits both potent dopamine D2 and 5-HT2 receptor blocking activity, as well as high affinity for alpha1 and alpha2 adrenergic receptors and histamine H1 receptor. We found that risperidone has a potent antinociceptive effect in the tailflick assay with an ED50 of 26.4 mg/kg. This effect of risperidone was antagonized by naloxone (P < 0.05). This sensitivity to naloxone indicates that at least some of the analgesic effects of risperidone are mediated by an opioid mechanism of action. beta-FNA (mu1 mu2-antagonist), naloxonazine (mu1-antagonist) and norbinaltorphamine (nor-BNI; kappa1-analgesia) reversed risperidone antinociceptive effect (P < 0.05). Naltrindole (delta-antagonist) only partially reversed risperidone antinociceptive effect. We found that the sensitivity of risperidone antinociceptive effect to selective antagonists implies involvement of mu1-, mu2- and kappa1-opioid and to a lesser extent delta-opioid mechanisms. These results suggest a possible role for risperidone both in the management of pain and in the management of opiate withdrawal and detoxification.
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PMID:Augmentation of opioid induced antinociception by the atypical antipsychotic drug risperidone in mice. 919 79

The effect of 5-HT2 receptor blocker ritanserine on the analgesic effect of morphine was studied in experiments on mice. A single simultaneous injection of ritanserine (10 mg/kg) and morphine (1, 10, and 20 mg/kg) prolonged the duration of analgesia in the tail clip test. Combined subchronic (6 days) injection of morphine and ritanserine (1, 5, and 10 mg/kg) twice a day delayed the development of tolerance to the opiate analgesic effect in the hot plate and tail clip tests.
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PMID:[Ritanserin prolongs the analgesic effect of morphine and slows the development of tolerance]. 920 58

5-hydroxytryptamine (5-HT) has been reported to modulate analgesia produced by opioids or electrical stimulation of the periaqueductal gray (PAG). 5-HT increases K+ conductance and inhibits the firing activity of the PAG neurons. We examined the electrophysiological and pharmacological characteristics of the K+ current involved in 5-HT-induced hyperpolarization of dissociated rat PAG neurons. Among the neurons tested, 5-HT activated inward K+ currents in 30-40%, whilst the remaining 60-70% did not respond to 5-HT. 5-HT activated an inwardly rectifying K+ current (I5-HT) in a concentration- and voltage-dependent manner. I5-HT was mimicked by a 5-HT1A receptor selective agonist, 8-OH-DPAT, and was reversibly blocked by a 5-HT1A receptor antagonist, piperazine maleate, but not by a 5-HT2 receptor antagonist, ketanserin. I5-HT was sensitive to K+ channel blockers such as quinine and Ba2+, but insensitive to 4-aminopyridine, Cs+ and tetraethylammonium. I5-HT was inhibited by GDP(beta)s and was irreversibly activated by GTP(gamma)s. I5-HT was significantly suppressed by N-ethylmaleimide and pertussis toxin, but not by cholera toxin. Second messenger modulators such as staurosporin, forskolin, and phorbol-12-myristate-13-acetate did not alter I5-HT. The present study indicates that 5-HT-induced hyperpolarization of the PAG neurons results from activation of the pertussis toxin-sensitive G-protein-coupled inwardly rectifying K+ currents through 5-HT1A receptors.
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PMID:5-HT1A receptor-mediated activation of G-protein-gated inwardly rectifying K+ current in rat periaqueductal gray neurons. 1148 54


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