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

The responses of primate spinothalamic tract (STT) neurons to innocuous and noxious mechanical stimuli applied to the skin can be enhanced for more than an hour following prolonged noxious stimulation. This increased responsiveness is thought to reflect sensitization of dorsal horn neurons and may help account for secondary hyperalgesia and mechanical allodynia. The proposal that central sensitization is due to the activation of second messenger system was tested in this study by examining the effect of trans-ACPD (trans-D,L-1-amino-1,3-cyclopentanedicarboxylic acid), an agonist of metabotropic excitatory amino acid (EAA) receptors, introduced into the dorsal horn by microdialysis. A low dose of trans-ACPD resulted in an increase in the responses of STT cells to an innocuous mechanical stimulus (BRUSH), but no increase in the responses to noxious mechanical and thermal stimuli or in the excitation produced by iontophoretically applied EAAs. A high dose of trans-ACPD caused a transient increase in background activity, but no change in the responsiveness of spinothalamic cells to any of the test stimuli. It is concluded that low doses of trans-ACPD can selectively enhance transmission through interneuronal pathways mediating tactile inputs to spinothalamic cells.
Pain 1994 Mar
PMID:The effect of trans-ACPD, a metabotropic excitatory amino acid receptor agonist, on the responses of primate spinothalamic tract neurons. 802 20

The present study examined the role of mGluRs in nociceptive responses of male Long-Evans rats following a subcutaneous (s.c.) injection of 1% (30 microliters) or 2.5% (50 microliters) formalin to the plantar surface of the hindpaw. Intrathecal (i.t.) administration of the mGluR4/mGluR6-mGluR8 agonist, L(+)-2-amino-4-phosphonobutyric acid (L-AP4), the mGluR1/mGluR5 antagonists. (S)-4-carboxyphenylglycine ((S)-4CPG) or (S)-4-carboxy-3-hydroxyphenylglycine ((S)-4C3HPG), but not the non-selective antagonist, (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG), to the lumbar spinal cord slightly reduced second phase nociceptive responses. An i.t. injection of the mGluR1/mGluR5 agonist, (RS)-3,5-dihydroxyphenylglycine ((RS)-DHPG) or the mGluR2/mGluR3 agonist, (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3S)-ACPD), but not (2S,1'R,2'R,3'R)-2-(2'3-dicarboxy-cyclopropyl)-glycine (DCG-IV), dose-dependently enhanced formalin-induced nociception in the second phase. In addition, the facilitation of nociceptive responses induced by (1S,3S)-ACPD or (RS)-DHPG was reduced by prior i.t. administration of the mGluR antagonists, (+)-MCPG or (S)-4C3HPG, respectively, as well as by the N-Methyl-D-aspartate (NMDA) receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid (D-AP5). These results indicate that although mGluRs may play a minor role in formalin-induced nociception, mGluR agonist-related facilitation of formalin scores may reflect an interaction with the NMDA receptor.
Pain 1996 Dec
PMID:The contribution of metabotropic glutamate receptors (mGluRs) to formalin-induced nociception. 912 12

We examined the pharmacological profile of 1-aminoindan-1,5-dicarboxylic acid (AIDA), a rigid (carboxyphenyl)glycine derivative acting on metabotropic glutamate receptors (mGluRs). In cells transfected with mGluR1a, AIDA competitively antagonized the stimulatory responses of glutamate and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD] on phosphoinositide hydrolysis (pA2 = 4.21). In cells transfected with mGluR5a, AIDA displayed a much weaker antagonist effect. In transfected cells expressing mGluR2, AIDA (< or = 1 mM) did not affect the inhibition of forskolin-stimulated adenylate cyclase activity induced by (1S,3R)-ACPD, but at large concentrations, it displayed a modest agonist activity. In rat hippocampal or striatal slices, AIDA (0.1-1 mM) reduced the effects of (1S,3R)-ACPD on phospholipase C but not on adenylate cyclase responses, whereas (+)-alpha-methyl-4-carboxyphenylglycine (0.3-1 mM) was an antagonist on both transduction systems. In addition, AIDA (0.3-1 mM) had no effect on mGluRs coupled to phospholipase D, whereas (+)-alpha-methyl-4-carboxy-phenylglycine (0.5-1 mM) acted as an agonist with low intrinsic activity. In rat cortical slices, AIDA antagonized the stimulatory (mGluR1-mediated) effect of (1S,3R)-ACPD on the depolarization-induced outflow of D-[3H]aspartate, disclosing an inhibitory effect ascribable to (1S,3R)-ACPD activating mGluR2 and/or mGluR4. Finally, mice treated with AIDA (0.1-10 nmol i.c.v.) had an increased pain threshold and difficulties in initiating a normal ambulatory behavior. Taken together, these data suggest that AIDA is a potent, selective and competitive mGluR1 a antagonist.
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PMID:Pharmacological characterization of 1-aminoindan-1,5-dicarboxylic acid, a potent mGluR1 antagonist. 915 78

Processing of nociceptive information can be modulated at various levels in spinal cord that may range from changes of neurotransmitter release from primary afferent Adelta- or C-fibres to excitability changes of spinal interneurones or motoneurones. The site and mechanism of action of spinal analgesics has been assessed with a number of in vivo and in vitro methods with sometimes conflicting results. Here, we have used transverse spinal cord slices with attached dorsal roots to simultaneously record mono- and polysynaptic Adelta-fibre-evoked field potentials in superficial spinal dorsal horn. Two classical spinal analgesics, morphine and clonidine, and the metabotropic glutamate receptor agonist (IS,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD) differentially affected mono- and polysynaptic Adelta-fibre-evoked transmission in spinal dorsal horn. Polysynaptic responses were dose-dependently inhibited while the monosynaptic response remained unaffected. These results suggest that spinal analgesics may preferentially affect polysynaptic but not monosynaptic Adelta-fibre-evoked responses in superficial spinal dorsal horn.
Pain 2000 Oct
PMID:Differential actions of spinal analgesics on mono-versus polysynaptic Adelta-fibre-evoked field potentials in superficial spinal dorsal horn in vitro. 1109 4

Drimanial, a new sesquiterpene isolated from the barks of the plant Drimys winteri (Winteraceae), given systemically, intraplantarly, or by spinal or supraspinal routes, produced pronounced antinociception against both phases of formalin-induced licking. The systemic injection of drimanial also inhibited, in a graded manner, the pain-related behaviours induced by intraplantar or intrathecal (i.t.) administration of glutamate. Moreover, drimanial also caused marked inhibition of the nociception induced by i.t. administration of a metabotropic glutamate agonist (1S,3R)-ACPD, without affecting nociceptive responses induced by ionotropic agonists (NMDA, kainate, AMPA) or by substance P. The antinociception caused by drimanial was not influenced by naloxone, nor did it interfere with the motor coordination of animals in the rota-rod test. Furthermore, drimanial caused graded inhibition of [(3)H]glutamate binding in cerebral cortical membranes from mice, with an IC(50) value of 4.39 micro M. Together, these results provide strong evidence indicating that the sesquiterpene drimanial produces antinociception in mice at peripheral, spinal and supraspinal sites. An interaction with metabotropic glutamate receptors seems to contribute to the mechanisms underlying its antinociceptive action.
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PMID:Evidence for the involvement of glutamatergic receptors in the antinociception caused in mice by the sesquiterpene drimanial. 1224 63

This study aimed to investigate further the mechanisms involved in the antinociception caused by dipyrone, given by intraperitoneal (i.p.) or intrathecal (i.t.) routes. The intraperitoneal administration of dipyrone to mice 30 min prior resulted in a significant and dose-related inhibition of the biting responses induced by i.t. injection of glutamate, trans-ACPD or substance P (SP). In addition, dipyrone given by i.t. route, 15 min before glutamate, trans-ACPD or SP, also produced a significant reduction in their nociceptive effects. In addition, dipyrone given by i.t. route, 15 min before glutamate, trans-ACPD or SP, also produced a significant reduction in their nociceptive effects. Dipyrone, given either systemically (i.p.) or by i.t. route also caused a dose-dependent inhibition of phorbol myristate acetate (PMA)-induced nociception. Given by systemic route, dipyrone inhibited PMA-induced paw oedema formation. Collectively, these results extend previous data from our group indicating that glutamatergic-mediated pain responses, specifically those mediated by metabotropic receptor subtype, together with inhibition of neurokinin NK(1)-mediated response, account for the antinociceptive action of dipyrone in mice. Furthermore, we have also produced experimental evidence indicating that the activation of the protein kinase C-dependent pathway plays a role in the dipyrone antinociceptive action.
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PMID:Evidence for the involvement of metabotropic glutamatergic, neurokinin 1 receptor pathways and protein kinase C in the antinociceptive effect of dipyrone in mice. 1501 64

The present study was designed to investigate further the mechanisms involved in the antinociception caused by diphenyl diselenide in behavioral model of pain in mice. Diphenyl diselenide (1-100 mg/kg), given orally, produced significant inhibition of the biting behavior induced by intrathecal (i.t.) injection of glutamate (175 nmol/site) and N-methyl-d-aspartate (NMDA; 450 pmol/site), with mean ID(50) values of 45.92 (39.74-60.4) and 55.77 (36.52-77.5) mg/kg respectively. However, diphenyl diselenide completely failed to affect the nociception induced by alpha-amino-3-hydroxy-5-mehtyl-4-isoxazolepropionic acid (AMPA; 135 pmol/site), (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD; 50 nmol/site) and kainate (110 pmol/site). This compound also reduced the nociceptive response induced by substance P (SP) (135 ng/site, i.t.), interleukin 1beta (IL-1beta; 1 pg/site), tumor necrosis factor-alpha (TNF-alpha; 0.1 pg/site), bradykinin (BK; 0.1 microg/site) and capsaicin (30 ng/site) with mean ID(50) values of 16.22, 7.06, 6.06, 4.18 and 7.90 mg/kg, respectively. Together, these results indicate that diphenyl diselenide produced antinociception at spinal sites, with a possible interaction with glutamatergic pathways, more specifically via interaction with NMDA receptors, peptidergic or vanilloid systems.
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PMID:Spinal mechanisms of antinociceptive action caused by diphenyl diselenide. 1761 8

Humirianthera ampla Miers is a member of the Icacinaceae family and presents great amounts of di and triterpenoids. These chemical constituents in roots of Humirianthera ampla sustain not only the ethnopharmacological use against snake venom, but also some anti-inflammatory and analgesic properties of the plant. In this study we investigated the antinociceptive action of the ethanolic extract (EE) from roots of the Humirianthera ampla in chemical and thermal models of pain in mice. The oral treatment with ethanolic extract dose-dependently inhibited glutamate-, capsaicin- and formalin-induced licking. However, it did not prevent the nociception caused by radiant heat on the tail-flick test. The ethanolic extract (30 mg/kg) caused marked inhibition of the nociceptive biting response induced by glutamate, (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD), N-methyl-d-aspartate (NMDA) and substance P. The antinociception caused by ethanolic extract was significantly attenuated by naloxone, l-arginine, WAY100635, ondansetron or ketanserin, but not by caffeine or naloxone methiodide. In conclusion, the ethanolic extract from roots of Humirianthera ampla produces antinociception against neurogenic and inflammatory models of nociception. The mechanisms of antinociception involve nitric oxide, opioid, serotonin and glutamate pathways. Therefore, our results support the ethnopharmacological use of the Humirianthera ampla against inflammatory and painful process caused by snake venom.
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PMID:Antinociceptive action of ethanolic extract obtained from roots of Humirianthera ampla Miers. 1790 Aug 39

(-)-Linalool is a monoterpene alcohol which is present in the essential oils of several aromatic plants. Recent studies suggest that (-)-linalool has anti-inflammatory, antihyperalgesic and antinociceptive properties in different animal models. The present study investigated the contribution of glutamatergic system in the antinociception elicited by (-)-linalool in mice. Nociceptive response was characterized by the time that the animal spent licking the injected hind paw or biting the target organ following glutamate receptor agonist injections. (-)-Linalool administered by intraperitoneal (i.p., 10-200 mg/kg), oral (p.o., 5-100 mg/kg) or intrathecal (i.t., 0.1-3 microg/site) routes dose-dependently inhibited glutamate-induced nociception (20 micromol/paw, pH 7.4) with ID(50) values of 139.1 mg/kg; 34.6 mg/kg; and 0.9 microg/site, with inhibitions of 70+/-4; 72+/-7 and 74+/-8%, respectively. However, the intraplantar injection of (-)-linalool partially (49+/-9%) inhibited glutamate-induced nociception. Furthermore, (-)-linalool (200 mg/kg) given i.p. also reduced significantly the biting response caused by intrathecal injection of glutamate (30 microg/site), AMPA (25 ng/site), SP (135 ng/site), NMDA (25 ng/site) and kainate (23.5 ng/site), with inhibitions of 89+/-6%, 73+/-11%, 85+/-4%, 98+/-2% and 52+/-15%, respectively. However, (-)-linalool did not inhibit nociception induced by intrathecal injection of trans-ACPD (8.6 microg/site). Taken together, these results provide experimental evidences indicating that (-)-linalool produce marked antinociception against glutamate induced pain in mice, possible due mechanisms operated by ionotropic glutamate receptors, namely AMPA, NMDA and kainate.
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PMID:Evidence for the involvement of ionotropic glutamatergic receptors on the antinociceptive effect of (-)-linalool in mice. 1857 2

The present study was designed to investigate further the mechanisms involved in the antinociception caused by bis-selenide in behavioral model of pain in mice. Bis-selenide (5-50 mg/kg), given orally, produced significant inhibition of the antinociceptive behavior induced by intrathecal (i.t.) injection of glutamate (175 nmol/site), kainate (110 pmol/site) and (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD; 50 nmol/site) and the maximal inhibitions observed were 57+/-5, 46+/-7 and 73+/-3%, respectively. Bis-selenide failed to affect the nociception induced by alpha-amino-3-hydroxy-5-mehtyl-4-isoxazolepropionic acid (AMPA; 135 pmol/site) and N-methyl-d-aspartate (NMDA; 450 pmol/site). This compound also reduced the nociceptive response induced by tumor necrosis factor-alpha (TNF-alpha; 0.1 pg/site), interleukin-1beta (IL-1beta; 1 pg/site), substance P (SP) (135 ng/site, i.t.) and capsaicin (30 ng/site) and the inhibitions observed were 81+/-3%, 88+/-1%, 77+/-3 and 67+/-3, respectively. The oral administration of bis-selenide (25-50 mg/kg) in mice caused a significant increase in the reaction time to thermal stimuli in the hot plate test and the mean ID(50) value (and the 95% confidence limits) was 20.37 (15.00-25.74) mg/kg. The antinociceptive effect caused by bis-selenide (50 mg/kg, p.o.) on the hot plate test in mice was reversed by intrathecal (i.t.) injection of some K(+) channel blockers such as tetraethylammonium (TEA, non-selective voltage-dependent K(+) channel inhibitor) and glibenclamide (ATP-sensitive K(+) channel inhibitor), but not apamin and charybdotoxin (large- and small-conductance Ca(2+)-activated K(+) channel inhibitors, respectively). Together, these results indicate that bis-selenide produces antinociception at spinal sites through the activation of ATP-sensitive and voltage-gated K(+) channels and interaction with kainate and trans-ACDP receptors as well as vanilloid and neuropeptide receptors and pro-inflammatory cytokines.
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PMID:Spinal mechanisms of antinociceptive effect caused by oral administration of bis-selenide in mice. 1868 Jul 35


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