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Discovery of non-peptide, small molecule antagonists of α9α10 nicotinic acetylcholine receptors as novel analgesics for the treatment of neuropathic and tonic inflammatory pain.

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A series of azaaromatic quaternary ammonium analogs has been discovered as potent and selective α9α10 nicotinic acetylcholine receptor (nAChR) antagonists. The preliminary structure-activity relationships of these analogs suggest that increased rigidity in the linker units results in higher potency

Physiological relevance and time course of a tonic endogenous opioid modulation of nociceptive messages, based on the effects of naloxone in a rat model of localized hyperalgesic inflammation.

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In a rat model of localized hyperalgesic inflammation induced by intraplantar injection of carrageenin, the effect of a relatively high dose of naloxone (1 mg/kg i.v.) was investigated using the measure of the vocalization threshold as a nociceptive test, on both the inflamed and non-inflamed paws.

mGluR activation reveals a tonic NMDA component in inflammatory hyperalgesia.

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Metabotropic glutamate receptors (mGluRs) have been shown to contribute to nociceptive processing in the spinal cord. We have investigated the pharmacology of the mGluR agonist (1S,3R)-ACPD during inflammatory hyperalgesia in an in vitro preparation of the juvenile rat hemisected spinal cord.

Tonic stimulation of the pharyngeal mucosa causes pain and a reversible increase of inflammatory mediators.

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OBJECTIVE To develop a model of the inflammatory component of non-infectious sore throat using tonic stimulation and quantification of inflammatory mediators in pharyngeal lavage fluid. METHODS Forty-five healthy volunteers. METHODS Cold dry air. METHODS Tonic stimulation of the pharynx was achieved

Thalamic ryanodine receptors are involved in controlling the tonic firing of thalamocortical neurons and inflammatory pain signal processing.

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Ryanodine receptors (RyRs) are highly conductive intracellular Ca(2+) release channels which are widely expressed in the CNS. They rapidly increase the intracellular Ca(2+) concentrations in neuronal cells in response to Ca(2+) influx through voltage-gated Ca(2+) channels. A previous study reported

Indicators of inflammation after recent tonic-clonic epileptic seizures correlate with plasma interleukin-6 levels.

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Cerebrospinal fluid (CSF) and peripheral blood pleocytosis have been observed after epileptic seizures without any evidence of infections, but no systematic studies on the acute phase reaction in such patients have been performed. We have previously reported increased levels of interleukin-6 (IL-6)

Tonic pupils: an unusual autonomic involvement in chronic inflammatory demyelinating polyneuropathy (CIDP).

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Chronic inflammatory demyelinating polyneuropathy (CIDP) is a neuropathy which affects mainly large myelinated axons and has a typically mild autonomic dysfunction mainly from postganglionic nerve fiber involvement.We report here an acute onset CIDP

Pro-inflammatory cytokines, IL-1β and TNF-α, produce persistent compromise in tonic immobility defensive behaviour in endotoxemia guinea-pigs.

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Sepsis has been associated with acute behavioural changes in humans and rodents, which consists of a motivational state and an adaptive response that improve survival. However, the involvement of peripheral cytokines synthesized during systemic inflammation as modulators of the tonic immobility (TI)

Electrophysiological identification of tonic and phasic neurons in sensory dorsal root ganglion and their distinct implications in inflammatory pain.

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In the mammalian autonomic nervous system, tonic and phasic neurons can be differentiated on firing patterns in response to long depolarizing current pulse. However, the similar firing patterns in the somatic primary sensory neurons and their functional significance are not well investigated. Here,

Anti-nociceptive and anti-inflammatory effects of a Nigerian polyherbal tonic tea (PHT) extract in rodents.

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The study investigated the anti-nociceptive and anti-inflammatory properties of a Nigerian Polyherbal Health Tonic tea aqueous extract (PHT) in rodents of both sexes. 100-500 mg kg(-1) of the aqueous extract was administered via the intra-peritoneal (i.p.) and oral (p.o.) routes to 5 groups of mice

Involvement of N-methyl-D-aspartate-type glutamate receptor epsilon1 and epsilon4 subunits in tonic inflammatory pain and neuropathic pain.

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N-methyl-D-aspartate receptors play an important role in nociceptive transmissions in various types of pain. In this study, we investigated the pain-related response in mice lacking the N-methyl-D-aspartate-type glutamate receptor epsilon1 or epsilon4 subunit in the formalin test and in the partial

Tonic pain response during inflammation and stress-induced corticosterone variations in prenatally stressed infant rats: effects of maternal buspirone injected during pregnancy.

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We studied the effects of injections of 5-HT1A-agonist buspirone to pregnant rats before stress exposure on corticosterone level in the dynamics of stress response to inflammatory-induced pain in 7-day-old offspring. During the period of the hypothalamic-pituitary-adrenal system hyporeactivity, the

Non-steroidal Anti-inflammatory Drugs in Tonic, Phasic and Inflammatory Mouse Models.

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The principal mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of ciclooxigenases. In this study was evaluated if NSAIDs could induce antinociceptive differences according to the type of murine pain model. Male mice were injected intraperitoneally with

RIPK1 is a critical modulator of both tonic and TLR-responsive inflammatory and cell death pathways in human macrophage differentiation.

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In this study, we took advantage of human-induced pluripotent stem cells (hiPSC) and CRISPR/Cas9 technology to investigate the potential roles of RIPK1 in regulating hematopoiesis and macrophage differentiation, proinflammatory activation, and cell death pathways. Knock-out of RIPK1 in hiPSCs

The vagus nerve: a tonic inhibitory influence associated with inflammatory bowel disease in a murine model.

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OBJECTIVE The recently proposed Inflammatory Reflex describes an interaction between the vagus nerve and peripheral macrophages, resulting in attenuation of proinflammatory cytokine release in response to systemic exposure to bacterial endotoxin. The purpose of this study was to determine whether a

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